Phẫu Thuật Tạo Hình (Tập 1): Nguyên Lý Cơ Bản – Neligan (Ấn bản 4)

415
Flap applications
allows choosing a well-vascularized skin flap, thin flap, pro­
vides a variety of flap design, and minimizes donor site
morbidity.
Lower extremity
Regional flaps:
1. Gastrocnemius
2. Soleus.
Distant flaps:
1. Cross-leg.
Perforator flaps:
1. Propeller flap
2. Distally based perforator flaps
3. Medial sural artery perforator (MSAP).
Reconstruction of the lower extremity remains particularly
challenging. Defects including exposed joints and prostheses,
infected bone, and fractures are common. Furthermore, the
availability of adequate soft tissue for coverage is limited,
particularly in the lower third of the leg.
There are two local sources of muscle or musculocutaneous
flaps available for reconstruction of the leg, the gastrocnemius
and the soleus muscles. The use of distant flaps involves
microvascular transplantation of various muscles or perfora­
tor flaps depending on the size of the wound and surgeon’s
preference. Many muscles have been described, including the
gracilis, latissimus dorsi, and rectus abdominis. In an effort
to minimize donor site, the anterolateral thigh flap, deep
inferior epigastric perforator flap and the superficial inferior
epigastric artery perforator flaps may be used as well. Cross-
leg flaps are also available but have largely been supplanted
by either local muscle flaps or microvascular composite tissue
transplantation.
The gastrocnemius is a type I muscle, consisting of a medial
and a lateral head. Each head has a wide arc of rotation
based on its single vascular pedicle (medial or lateral
sural vessels). The gastrocnemius muscle or musculocutane­
ous flap is the flap of choice for coverage of the knee and for
coverage of exposed bone or orthopedic hardware involving
the upper two-thirds of the leg.324,325 Defects of the middle
third of the leg can also be reconstructed with the gastrocne­
mius muscle.326–328 In patients with radical knee debridement
and loss or disruption of the extensor mechanism, the
gastrocnemius can be used to restore knee function (Figs.
22.66–22.67).329
The soleus muscle flap is utilized for reconstructing defects
involving the middle third of the leg. The soleus muscle is the
prime ankle plantar flexor and it serves to stabilize the ankle
in ambulation by opposing dorsiflexion.330 Because of com­
pensatory mechanisms, the use of the soleus muscle as a flap
does not impair function. Function-preserving techniques
such as muscle splitting is recommended if the soleus is used
in a patient who does not have a functional medial and lateral
gastrocnemius muscle.331,332 Defects of the proximal third can
be reached by the soleus, but require extensive mobilization
of the muscle.333 In the lower third of the leg, the soleus muscle
can be used as a proximally or distally based flap. In this
region, however, the soleus muscle flap is generally used for
smaller defects (Fig. 22.68). Larger defects require microvas­
cular tissue transplantation.
Fig. 22.62  The five zones of the abdomen are the periumbilical hub (green), the
epigastric (red), left and right lateral (yellow), and infraumbilical (blue). They are
shown with the preferred perforator flap for cutaneous coverage inscribed. ALT,
anterolateral thigh; DIEAP, deep inferior epigastric artery perforator; DSEAP, deep
superior epigastric artery perforator. (From Blondeel PN, Morris SF, Hallock GG,
Neligan PC. Perforator Flaps, 2nd edn. St. Louis: QMP; 2013.)
DSEAP
DIEAP
DIEAP or ALT
ALT
ALT
flap is useful for large, irradiated defects in the perineum
(Figs. 22.64 & 22.65).178,313,314
The gluteus maximus muscle provides stable coverage for
pelvic and perineal defects. Its large mass is particularly
useful for obliterating pelvic dead space and covering perineal
wounds; it is also useful for rectal sphincter reconstruc­
tion.315,316 The gluteus maximus fasciocutaneous V–Y advance­
ment flap is reliable for extensive vulvectomy and recurrent
rectal cancer defects (see Fig. 22.63).317,318 The gluteal thigh
flap, described by Hurwitz, includes the inferior part of the
gluteus maximus muscle and a large cutaneous territory of
the posterior thigh that is supplied by the descending branch
of the inferior gluteal artery.319 The gluteus maximus muscu­
locutaneous and gluteal fasciocutaneous flap is particularly
useful for reconstructing deep perineal and pelvic defects.320,321
Often perineal reconstruction can be complex, requiring
multiple flaps. One must decide the best choice of reconstruc­
tion as well as considering ideal donor sites. Due to the rich
available perforators of this region, many new flaps and
approaches have been introduced.322,323 These perforator flaps
can originate from the external and internal pudendal artery,
obturator artery, deep inferior epigastric artery, inferior gluteal
artery, descending branch of medial circumflex femoral artery,
and more. One can design a single or a multiple perforator
flap based on these perforators and tailor the reconstruction
according to the needs of the defect. This free-style approach

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CHAPTER 22 • Flap classification and applications
Fig. 22.63  (A–D) Bilateral gracilis and gluteal thigh flaps for reconstruction of a radiation defect of the perineum.
A
B
C
D
Fig. 22.64  Rectus abdominis flap.
(A) Arc to perineum. (B) Arc to internal
pelvis.
A
B

417
Flap applications
Fig. 22.65  (A–E) Rectus abdominis
musculocutaneous flap for groin coverage.
A
B
C
D
E
For small and moderate-sized defects with less extensive
dead space, a skin flap can be considered to restore function
and form. The donor site is usually limited to the same
extremity and the abundant perforators allow tailored recon­
struction. The propeller flap based on a single perforator can
be elevated as a fasciocutaneous or a skin flap harvested
above the fascia. The flap is designed around a perforator as
a pivot point and forming two blades with an unequal length
that can be rotated to fill the defect (Fig. 22.69). The ability to
rotate up to 180° makes it versatile for thigh and lower leg
defects. Fig. 22.70 shows a free-style perforator-based propel­
ler flap on the upper thigh rotated to reconstruct the mid
posterior thigh defect after cancer resection. An adequate flap
length can be secured by dissecting further into the source
vessel when needed, injury to the perforator avoided with
meticulous dissection, identification of a perforator with a
good pulse, surrounding tissues around the perforators suf­
ficiently released to minimize kinking, and supercharge or
turbocharge veins located distally in the flap to reduce venous
congestion. Although not ideal, skin graft on the donor site
may be needed when used in the lower leg. Nevertheless, the
simplicity and versatility of this approach may justify the
additional donor site morbidity. Some perforator flaps can be
extended by making them reverse pattern/distally based
flaps. When an ALT is elevated on a proximally located per­
forator and raised as a reverse pattern, the flap can easily
reach the distal part of the knee.334,335 The MSAP flap is another
flap that can reach the knee as a regional perforator flap.
When a line is drawn from the midpoint of the popliteal
crease to the apex of the medial malleolus, the first perforator
from the medial sural artery usually rises from a semicircle
with a 2 cm radius centered 8 cm distal to the popliteal crease
(Fig. 22.71).336 With an average length of 8 cm, the flap can
easily reach the knee.
Foot
Regional flaps:
1. Flexor digitorum brevis
2. Abductor hallucis

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CHAPTER 22 • Flap classification and applications
Fig. 22.66  Gastrocnemius flap. Arc to knee and upper third of leg.
A
B
Fig. 22.67  (A–D) Gastrocnemius musculocutaneous flap for knee and proximal third of tibia defect.
A
B
C
D

419
Flap applications
vascular, neurosensory, and weight-bearing status. For small
defects, skin grafts are often the procedure of choice provided
that there is adequate protective soft tissue within the bed of
the defect. For small defects involving weight-bearing areas,
axial innervated skin flaps and fasciocutaneous flaps have
been successful in providing stable coverage.143,337 For the
deeper, more extensive foot defect, the use of a muscle or
musculocutaneous flap is usually necessary. The local muscles
available for use as flaps include the flexor digitorum brevis,
the abductor hallucis, and the abductor digiti minimi. These
muscles are small and are inadequate for larger defects. The
use of a distant muscle (e.g., cross-foot flap) or microvascular
free tissue transfer is usually necessary for coverage of any
major wound (those with excessive size and depth or with
component loss).
Mathes et al. demonstrated the anatomy of the flexor digi­
torum brevis for use as a flap in 1974.15 It is a type II muscle
that measures approximately 10 × 4 cm. This muscle was then
shown to be clinically useful to cover a calcaneal defect in
1974 by Vasconez et al.19 In 1980, Hartrampf et al. described
a modification of this technique, using the muscle as an
island flap that increased the arc of rotation. As an island flap
based on the lateral plantar artery, the flexor digitorum brevis
muscle reaches the malleolus and can cover the entire postero­
superior aspect of the heel pad.338 The authors recommended
that the patency of both the dorsalis pedis and the tibialis
posterior artery should be confirmed before the lateral plantar
artery is divided. In patients who have occlusion of either the
dorsalis pedis or the tibialis posterior artery, the lateral plantar
artery serves as a vital conduit of collateral flow and should
not be divided for flap use. The flexor digitorum brevis, when
transposed as a muscle flap, may provide stable coverage
and is of benefit in both diabetic and nondiabetic patients
(Fig. 22.72).339,340
Fig. 22.68  Soleus flap. (A,B) Arc to middle third of leg.
A
B
Fig. 22.69  The propeller flap based on a single perforator can be elevated as a
fasciocutaneous or a skin flap harvested above the fascia. The flap is designed
around a perforator as a pivot point and forming two blades with an unequal length
that can be rotated to fill the defect.
3. Abductor digiti minimi
4. Lateral calcaneal artery flap.
Defects of the foot are most often due to trauma or the long­
standing effects of underlying systemic disorders such as
diabetes mellitus and peripheral vascular disease. These
wounds can be extremely difficult to treat and often are best
left uncovered until the underlying disease is treated (e.g., by
revascularization). For some patients with severe, irreversible
underlying systemic disease, local conservative wound care
may be the only appropriate form of therapy.
When reconstruction is necessary, several issues must be
addressed, such as the size of the defect and the patient’s

420
CHAPTER 22 • Flap classification and applications
The retrograde lateral plantar artery flap was described by
Reiffel and McCarthy in 1980.341 The flap is fashioned by
dividing the lateral plantar vessels proximally; the plantar
fascia and the flexor digitorum brevis muscle can be elevated
as a flap based on distal retrograde flow. This flap is particu­
larly useful for coverage of medial and lateral metatarsal head
defects.342
The abductor hallucis is a type II muscle with branches of
the medial plantar artery as its dominant vascular supply.15
Based on this vascular pedicle the abductor hallucis can be
elevated as a muscle or musculocutaneous flap, and it can
reach defects just inferior to the medial malleolus as well
as defects of the proximal medial aspect of the dorsum of
the foot. Like the lateral plantar artery, the medial plantar
artery should not be divided if either the dorsalis pedis or
the posterior tibial artery is occluded. The abductor hallucis
muscle flap may be distally based to reconstruct forefoot
defects.343
Fig. 22.70  A patient is shown with a defect after
sarcoma resection of the posterior aspect of the
mid thigh. A perforator is mapped out using
Doppler nearest to the defect (A). After checking
the status of the perforator (B), a free-style
perforator-based propeller flap on the upper thigh
is designed, elevated and rotated to reconstruct the
mid-posterior thigh defect (C,D).
A
B
C
D
Fig. 22.71  The MSAP flap. The illustration shows that the first perforator is usually
detected 8 cm from the midpoint of the popliteal crease within a distal half circle
drawn with a 2 cm radius. m, medial malleolus; p, midline of popliteal crease.
(Adapted from Kim HH, Jeong JH, Seul JH, Cho BC. New design and identification
of the medial sural perforator flap: an anatomical study and its clinical applications.
Plast Reconstr Surg. 2006;117:1609–1618.)
p
m
r = 2.0 cm
8.0 cm

421
Flap applications
The regional flaps used for reconstruction of midline and
posterior trunk defects include three pairs of posterior trunk
muscles: trapezius and latissimus dorsi muscle flaps for the
upper and mid posterior trunk defects and the latissimus
dorsi and gluteus maximus muscle turnover flap for the
lower posterior trunk (Fig. 22.73). All three muscles have
large cutaneous territories that allow them to be used as
musculocutaneous flaps.348 In addition, other options include
the scapular flap, parascapular flap, and the paraspinous
muscle flap (Table 22.15). The selection for each of these
regional muscle flaps must be made first by evaluating the
defect and then selecting the relevant flap based on the
understanding of the anatomy and the arc of rotation. These
approaches may end up with too much tension and poor
tissue vascularity of the flap that may be designed beyond
the angiosome territory. In complex cases, it may require
multiple flap or two-layered reconstruction resulting in
increased risk of donor site morbidity.348 It can be critical for
patients that may undergo radiation therapy to heal properly
after the initial reconstruction. Although there are multiple
muscle groups in the posterior trunk, reconstruction remains
difficult using regional flaps.
The concept of perforators has allowed a new dimension
in reconstructive surgery. It defines the vascular supply for a
skin island from a single perforator penetrating the deep
muscle fascia while sparing tissues surrounding the pedicle.
The propeller flap intentionally rotates the flap based on a
single perforator resulting in an effective transposition.59,60,349
By designing with accuracy, this perforator-based propeller
flap can be used locally to cover various defects of the back
without injuring muscle function, provides sufficient bulk to
obliterate dead space, and can be closed primarily leading to
minimal donor site morbidity (Fig. 22.74).188 With the under­
standing that any perforator can be used as a flap, the free-
style flap leads to flexible design of propeller flaps enhancing
the chance for prompt reconstruction. The two major vascular
systems of the back are from the intercostal artery and the
lumbar artery perforators. According to the report by Saint-
Cyr’s group, in the lumbar region, two major areas of
The abductor digiti minimi is a type II muscle with branches
of the lateral plantar artery as its dominant vascular pedicle.15
This small muscle based on its dominant pedicle can reach
defects adjacent to the lateral malleolus. However, because of
its size, the flap is limited in its ability to provide coverage of
larger defects. In 1985, Yoshimura et al. reported the use of a
distally based abductor digiti minimi muscle flap.344 This
muscle flap based distally on the communication between the
lateral plantar artery and the plantar arch can be used to cover
small defects of the distal half of the foot. The abductor digiti
minimi may be harvested with the lateral calcaneal artery
sensate skin flap to cover plantar heel wounds.345
The lateral calcaneal artery is the terminal branch of the
peroneal artery. The flap can be designed as a fasciocutaneous
peninsula flap 4 cm wide extending from lateral malleolus to
anterior Achilles tendon. The flap can extend vertically from
lateral malleolus to the plantar surface of heel.346,347 After the
transposition of the flap, the donor site frequently needs skin
graft coverage.
Posterior trunk
Regional flaps:
1. Trapezius
2. Latissimus dorsi
3. Gluteus maximus
4. Scapular and parascapular
5. Paraspinous muscle.
Perforator flaps:
1. Intercostal artery perforators
2. Lumbar artery perforators.
Fig. 22.72  Flexor digitorum brevis flap. Arc to heel.
Table 22.15  Regional flaps for posterior trunk midline defects
Wound location
Muscle flap
Cervical
Trapezius muscle flap
Latissimus dorsi flap
High thoracic
Small defect
Large defect
Trapezius muscle with split-thickness skin
graft
Latissimus with skin island
Trapezius muscle (deep layer)
Thoracic
Small defect
Latissimus advancement flap
Reverse latissimus dorsi flap
Paraspinous turnover flap
Large defect
Latissimus dorsi with skin island
Thoracolumbar
and low lumbar
Latissimus dorsi with skin island
Unipedicled latissimus
Composite latissimus and gluteus maximus
Paraspinous turnover flap

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CHAPTER 22 • Flap classification and applications
Fig. 22.73  (Left) The common flaps that can be used to reconstruct an upper thoracic cervical defect include (A) the trapezius muscle flap and (B) the latissimus dorsi
flap. (Center) the common flaps that can be used to reconstruct a midthoracic defect include the (A) trapezius muscle flap, (B) latissimus dorsi flap, and (C) paraspinous
turnover flap. (Right) Defects in the lower lumbar area can be reconstructed with (A) a reversal lattismus dorsi flap with skin island, (B) a composite lattisimus and gluteus
maximus flap, or (C) a superiorly based gluteus flap. (Adapted from Mathes DW, Thornton JF, Rohrich RJ. Management of posterior trunk defects. Plast Reconstr Surg.
2006;118:73e–83e.)
A
A
A
B
B
B
C
C
perforators are clustered within 10–20 cm of the coccyx and
10 cm from the midline. In the thoracic region, perforator
location is clustered similarly distant from the midline at
10 cm, and 0–15 cm from C7.350 Any one of these perforators
can be based as a perforator flap but the perforator with the
strongest pulse and diameter may have a better flow to the
skin flap and may be the preferable choice as pedicle.351 Other
sources can be perforators from the superior epigastric artery,
deep inferior epigastric artery, superficial inferior epigastric
artery, superior circumflex iliac artery, deep circumflex iliac
artery and the superior gluteal artery.350,352 In cases where a
large dead space is present, one can epithelialize the skin
flap to obliterate it. Multiple perforator flaps can be elevated
and rotated if the defect is too large for a single flap
application.353
Pressure wounds
Regional flaps:
1. Gluteus maximus.
Distant flaps:
1. Tensor fascia lata
2. Gracilis
3. Hamstrings
4. Omentum.
Perforator flaps:
1. Sacral region:
Superior gluteal artery perforator (SGAP)
Inferior gluteal artery perforator (IGAP)
Lumbar artery perforator (LAP)
Parasacral artery perforator (PSAP)
Lateral intercostal artery perforator (LICAP)
2. Ischial region:
Inferior gluteal artery perforator (IGAP)
Adductor perforator
3. Trochanteric region:
Anterolateral thigh (ALT) perforator
Profunda femoris artery perforator (PFAP).
The gluteus maximus is a regional flap commonly used for
the surgical treatment of pressure sores. It is a type III muscle
and it is the flap of choice for reconstructing deep sacral
and ischial pressure sores. Function-preserving techniques
such as bilateral advancement flaps using only the superior
halves of the gluteus maximus for sacral coverage are recom­
mended for the ambulatory patient.49,354,355 Variations in
technique, including the sliding gluteus maximus flap, the
transposition gluteus maximus flap, and island flaps based on

423
Flap applications
Fig. 22.74  Freestyle propeller flaps based on a single perforator with accurate design allows coverage of various defects of the back without injuring muscle function,
provides sufficient bulk to obliterate dead space and can be closed primarily leading to minimal donor site morbidity. A patient with a defect of the upper back is shown
(A). After identifying a perforator using Doppler, the design is completed to cover the defect and then elevated based on a single perforator (B,C). The patient is shown to
have good contour and minimal donor site morbidity during follow-up (D).
C
D
A
B
musculocutaneous perforating vessels (muscle preserving)
have been described.355–358 The sliding flap is indicated for
small sacral defects, whereas the transposition flap (unilateral
or bilateral) is generally appropriate for larger defects because
it has a greater range of coverage. For extensive pressure
sores, the gluteal thigh flap has also been useful.319,320,359,360
More recently, the superior gluteal artery perforator flap
has been used for the treatment of sacral pressure ulcers.361 It
affords the same skin as the gluteus maximus myocutaneous
flap with the advantage that the muscle is completely spared
and the pedicle length significantly increased. This is a par­
ticularly attractive alternative in the ambulatory patient.
Three distant muscles used in the reconstruction of pres­
sure sores are the tensor fascia lata, gracilis, and the ham­
strings. The tensor fascia lata (TFL) is a type I muscle that is
useful for reconstructing trochanteric pressure sores.285,357,362 It
is also a reliable alternative flap for ischial defects because of
the following advantages: there is relatively low donor site
morbidity, especially in an ambulatory patient; the flap pro­
vides vascularized, durable fascia; and the flap can provide
sensibility in certain instances.
Several investigators have described the use of the
innervated TFL flap, based on the lateral femoral cutaneous
nerve (L2–L3), for reconstruction of ischial defects. They
have reported successful restoration of protective sensibility
without recurrence of pressure ulceration in paraplegic
patients with lesions below the L3 level.284,363,364
The major disadvantage of the TFL flap is its relative thin­
ness, a problem for the deeper pressure sore. In 1981, Scheflan
described a technique to increase the bulk of the TFL flap. By
de-epithelializing the distal aspect of the flap and folding the
inferior portion of the flap underneath, part of the flap gains
bulk. Used as a “sandwich”, the modified flap can usually fill
the deeper defect.365 Modifications in the design of the TFL
flap have been described in an attempt to minimize the donor
site morbidity. Problems such as dog-ears, excessive tension
at wound closure, skin necrosis at certain wound margins,
and the need for skin grafts have prompted techniques such
as the use of a bilobed TFL flap366 and the V–Y retroposition
TFL flap.367,368 These modifications appear to facilitate donor
closure in certain instances.
The gracilis is a type II muscle, first described in 1972 by
Orticochea for use as a musculocutaneous flap.369 In the treat­
ment of pressure sores, the gracilis is used primarily to repair
the ischial defect.370,371 Use of the gracilis does not preclude
the future use of the gluteus maximus or the posterior thigh
flap if the ulcer recurs. The muscle can be elevated with the
patient prone, but the distal muscle should be located before

424
CHAPTER 22 • Flap classification and applications
the skin island is incised, in order to ensure the correct local­
ization of the skin overlying the muscle (Figs. 22.75 & 22.76).
The gluteus maximus muscle (type III) is well situated for
coverage of both sacral and ischial pressure sores. There are
a number of modifications for its design and use for both
ischial and sacral pressure sores. In general, it is preferable to
use segmental transposition, reserving the superior half of the
muscle based on the superior gluteal artery and associated
venae comitantes for the sacral sore and the inferior half based
on the inferior gluteal artery and associated venae comitantes
for the ischial sore.
For the sacral sore, the cutaneous territory of the superior
half of the muscle may be used as a V–Y advancement flap,
or the skin island may be designed distally (near the muscle
insertion) for use as a transposition flap or proximally (near
the muscle origin) in V–Y advancement flap. For V–Y advance­
ment flap, the superior half of the muscle’s origin and inser­
tion is divided so the composite of muscle plus the overlying
soft tissue will cover the debridement site of the sacral decu­
bitus. Although perforating vessels will allow bilateral V–Y
advancement of the skin island with release of the muscle,
adequate well-vascularized soft tissue and muscle are required
to provide a long-lasting stable coverage over the sacrum
(Figs. 22.77 & 22.78). When it is used as a transposition flap,
the skin island and underlying muscle are transferred 180° to
provide sacral coverage. It is not necessary to divide the
superior muscle origin, although partial to complete release
of the origin allows easier flap inset over the sacrum. As
already mentioned, the SGAP flap has emerged as a useful
alternative to the musculocutaneous flap.
The inferior half of the gluteus maximus is ideal for ischial
sore coverage. The skin island is designed near the muscle
Fig. 22.75  Gracilis flap. Arc of rotation to the perineum.
A
B
C
Fig. 22.76  (A–C) Gracilis musculocutaneous flap for ischial pressure sore
coverage.

425
Flap applications
the posterior thigh. These muscles originate from the ischial
tuberosity, although the biceps femoris also has a short head
originating from the linea aspera of the femur. As a group,
these muscles are useful in the reconstruction of ischial pres­
sure sores. Used as a transposition flap, depending on the
size of the defect, one or more of the hamstring muscles
can provide ischial coverage. Hurteau et al. described V–Y
advancement of the hamstring musculocutaneous flap for
reliable coverage of the ischial pressure sore.372 A triangular
island of skin overlying the hamstring muscles is designed
with the base of the triangle at the inferior margin of the
ischial defect. The hamstring muscles are divided distal to the
skin island, and the entire muscle group is mobilized superi­
orly. The origins of the hamstring muscles are detached from
the ischium, thus enabling further advancement, and the flap
is sutured into place. Long-term results reveal stable coverage
of ischial pressure sores.373
The standard of muscle or musculocutaneous flaps to
reconstruct the sores of the pelvic region is now being
challenged by application of perforator or fasciocutaneous
flaps.58,63,361,374–378 The use of perforator flaps for this region
preserves the muscle function as it is spared during elevation,
avoids a midline scar on the mid sacrum which can frequently
break when using V–Y flaps, and enables the reconstruction
of recurrent pressure sores as there are multiple perforators
around the defect. Fig. 22.80 shows the angiosome of the
buttock and the potential perforator flaps which can be used
in this region.378
The GAP flap is based on either superior or inferior gluteal
artery perforators. Using a hand-held Doppler or CT angio­
gram, one can identify potential perforators around the sacral
defect (Fig. 22.81A). After the initial design of the flap based
on the perforator, an incision should be made on one edge.
Exploration for the perforator to the skin is performed either
by a subfascial or superfascial approach. If there is no adequate
perforator, one can always revert to using the flap as a simple
rotation flap, hence the one-edge incision (Fig. 22.81B). After
identifying the perforator, the final design should be made to
completely cover the defect. Incision is then made for the rest
of the margin and the perforator dissected. Once adequate
length is secured, the skin or the fasciocutaneous flap based
on the perforator can be easily rotated as a propeller to cover
the defect and close the donor site primarily (Fig. 22.81C). If
a single flap is not enough to cover the defect while achieving
primary closure of the donor site, multiple flaps can be used
to close the defect as well as achieve primary closure of the
donor site. Similar approaches can be made for the lumbar
artery perforator (LAP), parasacral artery perforator (PSAP),
and lateral intercostal artery perforator (LICAP) flaps based
on their perforator and the site of the defect.
The adductor perforator flap can be used as an island flap
to cover a perineal defect or ischial sores. Due to its location,
this perforator is frequently spared from previous surgeries
and injuries. The cutaneous perforator of the adductor magnus
muscle could be reliably found 8 cm distal to the groin crease
and 2 cm posterior to the posterior border of the gracilis
muscle. The pedicle length can be long as 8–9 cm, making it
easy to reach the ischial sores.58,376 This flap can be bulky due
to the excessive subcutaneous fat but can be debulked to fit
the defect.
The posterior thigh, like the anterior, lateral and medial
thigh, possesses rich perforators. The largest skin territory of
insertion. After splitting of the muscle, the muscle and overly­
ing skin island are easily rotated 90° to the ischial defect. The
condensed bulk of the muscle and its specific cutaneous ter­
ritory provide stable coverage at the ischial site of reconstruc­
tion (Fig. 22.79; see also Fig. 22.9).
The hamstrings, consisting of the biceps femoris, semi­
membranosus and semitendinosus, are a group of muscles of
Fig. 22.77  Gluteus maximus–gluteal thigh flap. (A) V–Y segmental muscle
advancement (superior half of gluteus maximus muscle). Flap advancement for
sacral coverage. (B) V–Y segmental muscle advancement (inferior half of gluteus
maximus muscle). Flap advancement for sacral coverage.
A
B

426
CHAPTER 22 • Flap classification and applications
Free perforator flaps
Anterolateral thigh (ALT)
The ALT flap remains as one of the most commonly used
perforator flaps for reconstruction. The perforator is found in
a relatively constant region and the pedicle can be long when
harvested with the source vessel. It also can be used as a
compound flap with the vastus lateralis muscle and the deep
fascia can be used to reconstruct the tendon defects. It is
widely used for head and neck reconstruction and extremity
reconstruction.
A line is drawn between the anterior superior iliac spine
and superior lateral border of the patella on the donor thigh.
The perforator branches are identified with Doppler near the
midpoint of this line. According to our clinical experience,
about 90% of perforators are found within 3 cm diameter
drawn at the midpoint of the line (Fig. 22.82).67,383–385 The skin
the posterior thigh comes from the profunda femoris artery,
especially the first and second perforating arteries out of the
four.58,378–380 Any of the perforators can be potentially used as
a regional flap to cover the trochanteric and ischial defects.
These flaps are evolved from the fasciocutaneous flaps of the
posterior thigh.320,359,381,382
Microsurgical application of flaps
Basically all local flaps can be elevated on a pedicle as a free
flap. The technique of microsurgery is critical along with the
steps involved during the preoperative, intraoperative and
postoperative period. These critical steps will be reviewed in
other chapters. Most of the muscle and musculocutaneous
flaps have been covered in the regional flap section. In this
section, we will briefly review common perforator flaps that
are used as free flaps.
Fig. 22.78  (A–E) Gluteus maximus
musculocutaneous flap for treatment of a sacral
pressure sore.
A
B
C
D
E

427
Flap applications
Fig. 22.79  (A–E) Inferior half of the gluteus maximus musculocutaneous flap for
ischial coverage.
A
B
C
D
E

428
CHAPTER 22 • Flap classification and applications
pedicle length can be up to 20 cm, with maximal dimensions
up to 40 × 20 cm.67,386 There have been some reports of variants
where the dominant perforator to the ALT flap may originate
from the transverse, oblique and ascending branch of the
lateral circumflex femoral artery.387 Thus, a free-style elevation
approach to accommodate these variations may be war­
ranted.27 The ALT flap is also an excellent local flap where it
flap is designed to include the perforator and is then elevated
from the medial border of the flap. The incision is made
through the deep fascia when elevated subfascially and raised
until the intermuscular septum between the rectus femoris
and vastus lateralis muscle is reached. At that point, the
descending branch of the lateral femoral circumflex is explored
along with the perforator to the skin flap (Fig. 22.83). The
Fig. 22.80  Angiosome of the buttock
and the potential perforator flaps
which can be used in this region.
Key: Orange, lumbar; top blue,
superior gluteal; top green, lateral
sacral; top purple, internal pudendal;
yellow, inferior gluteal; lateral green,
lateral circumflex femoral; lower blue,
adductor; aqua, profunda; lower
purple, source vessels. (Image from
Pan WR, Taylor GI. The angiosomes of
the thigh and buttock. Plast Reconstr
Surg. 2009;123:236–249.)
External
iliac artery
Internal iliac
artery
Common
iliac artery
Superior
gluteal
artery
Interior
gluteal
artery
Common
femoral
artery
Medial
circumflex
femoral
artery
Profunda
femoris
artery
Superficial
femoral
artery
Popliteal
artery
GM
G
SM
ST
BF
GMe
Fig. 22.81  (A) A patient with a pressure sore. After identifying a perforator near the defect, in this case an inferior gluteal artery perforator, the rest of the flap is designed
based on the free-style principle and then rotated to cover the defect (B,C).
A
B
C

429
Flap applications
has developed in an effort to perform a safe, reliable, repro­
ducible reconstruction with low donor-site morbidity.53,55,56,64
The DIEAP flap is now one of the first-line choices for autolo­
gous breast reconstruction. The deep inferior epigastric artery
(DIEA) arises from the terminal aspect of the external iliac
artery deep to the inguinal ligament then ascends from the
lateral aspect of the rectus abdominis muscle toward the
umbilicus. It ascends between the transversalis fascia and
the peritoneum before penetrating the rectus abdominis
muscle. The artery enters the middle third of the muscle most
frequently (78%), with the lower (17%) and upper third (5%)
less frequently.390 After penetrating the muscle, it gives off an
average of five (plus or minus two) perforators supplying the
skin. Most of the perforating vessels are found within 2 cm
cranial and 6 cm caudal and between 1 and 6 cm around the
lateral aspect of the umbilicus.58,391,392 The lateral perforators
may be larger and easier to dissect, but the midline perfora­
tors supply better blood flow to zone III and to zone IV.
Preoperative planning consists of the flap design in which
the proposed skin island should be centered over the identi­
fied perforators. Hand-held Doppler can be used to identify
the perforators assisting the flap design. CT angiograms may
help to choose the perforator with the best diameter and the
least dissection of the muscular segment (Fig. 22.84).
The incisions are carried down to the abdominal fascia.
Scarpa’s fascia is carefully maintained, and beveling is per­
formed at the lateral aspects and at the level below Scarpa’s
fascia only. Using electrocautery, the flap may quickly be
raised at the suprafascial level to the lateral border of the
anterior rectus fascia. When a perforator is encountered, the
caliber and location of the vessels are assessed and if possible
should be maintained until the largest perforator can be
selected (Fig. 22.85).56,62 Then the dissection continues through
the anterior rectus fascia and the rectus muscle reaching the
source vessel (Fig. 22.86). Efforts should be made to minimize
muscle and nerve injury if possible. Based on a single perfora­
tor, although this may vary between individuals, the flap
dimension can reach 30–45 cm in width and 11–16 cm in
can reach the lower abdomen, pelvis, perineum and the knee
by a reverse flow pattern.388 The flap can be harvested either
as a perforator flap which includes only the perforator branch
to the skin or as combined flap including the vastus lateralis
muscle based on the descending branch of the lateral femoral
circumflex system. The skin paddle can be defatted to about
5–8 mm thickness. The motor branch of the femoral nerve
running medial to the descending branch of the lateral cir­
cumflex femoral artery should be preserved. To elevate as a
sensate flap, a branch of the lateral femoral cutaneous nerve
should be included. The donor site can be primarily closed
depending on the laxity of the skin.
Deep inferior epigastic artery perforator (DIEAP) flap
The DIEAP flap evolved from the abdominal flaps as a free
flap by Holmstrom and the pedicled flap by Hartrampf
et al.223,389 Koshima and Soeda reported the first clinical use of
the lower abdominal skin and fatty tissue for breast recon­
struction without sacrificing rectus muscle and, since then, the
use of perforator flaps for autologous breast reconstruction
Fig. 22.82  A line is drawn between the anterior superior iliac spine and superior
lateral border of the patella on the donor thigh. The perforator branches are
identified with Doppler near the midpoint of this line. According to our clinical
experience, about 90% of perforators are found within 3 cm diameter drawn at the
midpoint of the line.
Fig. 22.83  Descending branch of the lateral femoral circumflex artery is explored
along with the perforator to the skin flap.
Fig. 22.84  CT angiograms may help to choose the perforator with the best
diameter and the least dissection of the muscular segment.

430
CHAPTER 22 • Flap classification and applications
Fig. 22.85  When a perforator is encountered, the caliber and location of the
vessels are assessed and if possible should be maintained until the largest
perforator can be selected.
Fig. 22.86  The dissection continues through the anterior rectus fascia and the
rectus muscle reaching the source vessel.
height.393 The donor site can be primarily closed depending
on the laxity of the skin.
Thoracodorsal artery perforator (TDAP) flap
One of the most popular muscle flaps has been the latissimus
dorsi muscle flap due to its constant vascular anatomy, big
bulk of muscle and the ability to be harvested with a skin
paddle. The same anatomy applies to the TDAP flap but
without the need to sacrifice the muscle, thereby minimizing
donor site morbidity and making it one of the workhorse
perforator flaps.58,394 The flap can be harvested horizontally,
longitudinally and in a bilobed shape but the dimension of
the flap may be limited by the need for primary closure. This
flap is commonly used for reconstruction of soft tissue.
The flap can be harvested in a supine position with the
shoulder slightly supported by a pillow and the arm fixed in
90° abduction but the lateral decubitus position allows the
flap to be harvested easily. Marking the anterior border of the
latissimus dorsi muscle increases the possibility to include all
perforators from this region. One can also use the Doppler to
mark the perforators. Incision begins with the anteroinferior
border of the skin paddle allowing identification of the ante­
rior border of the latissimus dorsi muscle and adjustment of
the flap design accordingly to place the anterior margin of the
skin paddle in front of the anterior border. The main perfora­
tors overlie in the course of the descending branch of the
thoracodorsal artery.395 After the perforator with the largest
caliber and pulse, one can dissect the muscle toward the
source vessel (Fig. 22.87). Pedicle length can be obtained up
to 14–18 cm including the thoracodorsal vessels and skin
dimensions can be up to 14 × 25 cm.58,396 The donor site can be
primarily closed depending on the laxity of the skin.
Complications
Complications with the use of flaps fall into three categories:
judgment, technique, and patient management. The most
Fig. 22.87  Marking the anterior border of the latissimus dorsi muscle increases
the possibility of including all perforators from this region. One can also use the
Doppler to mark the perforators. Incision begins with the anteroinferior border of the
skin paddle allowing identification of the anterior border of the latissimus dorsi
muscle and adjustment of the flap design accordingly to place the anterior margin
of the skin paddle in front of the anterior border.
Axillary vessels
Thoracodorsal artery
Thoracodorsal perforator
Thoracodorsal perforator
Lateral intercostal
sensory nerves/
posterior rami
Lateral intercostal
sensory nerves/
anterior rami
Lateral intercostal
perforators

431
Complications
common complications include seroma, hematoma, superfi­
cial skin necrosis, wound separation, inadequate coverage of
the defect, infection, and partial or complete loss of the flap.
By analyzing these complications in relation to judgment,
technique, and patient management, the surgeon should be
able to understand the cause of each complication in order to
prevent subsequent complications.
Errors in surgical judgment are usually due to: inadequate
preparation, inadequate flap design, or inadequate knowledge
of anatomy.
Inadequate preparation is characterized by proceeding
with a reconstructive procedure without having sufficient
resources to perform the operation. For example, a surgeon
may be asked to evaluate an elderly patient who has an
extensive nonhealing ulcer involving the distal third of the
leg. The surgeon recommends microvascular transplantation
of a muscle flap, yet foregoes a preoperative arteriogram even
though the patient has significant risk factors for peripheral
vascular disease. Intraoperatively, adequate recipient vessels
cannot be found and the flap is therefore aborted. This under­
scores the importance of preoperative preparation, especially
if the diagnostic study directly impacts the surgical procedure
planned.
Inadequate flap design is usually due to the surgeon’s
failure to account for every aspect of the surgical defect. The
flap should not be designed and elevated prior to debridement
of the wound. This may result in a significantly larger wound
and an inadequately small flap. The flap should only be
designed and elevated after the defect is completely debrided.
Inadequate knowledge of surgical anatomy may result in
damage to the vascular pedicle during dissection, which can
lead to failure of the flap. In addition to directly injuring the
vascular pedicle, the surgeon can indirectly injure a pedicle
by using a flap whose vascular pedicle is within the zone of
injury, as in defects involving infection and radiation necrosis.
Vascular pedicles within this environment may be compro­
mised. For example, in a distally based flap, the minor pedicle
is usually close to the defect and may be affected by the
underlying cause of the defect. This is one reason that a dis­
tally based flap is less reliable than the muscle flap that is
based on its dominant, major, or segmental secondary vascu­
lar pedicles. Through an appreciation of these subtle anatomic
differences, proper flap selection and safe flap transposition
can be achieved. It is imperative that the surgeon understand
the precise anatomy of the muscle and musculocutaneous flap
and the relationship to its vascular pedicle(s).
Surgical technique directly affects the outcome of any
procedure. The handling of tissue, particularly vascular ped­
icles, is of utmost importance to the success of the flap. Vessels
can be injured at any stage of the operation and are subject to
spasm, kinking, shearing, and twisting. One preventative
measure is the placement of temporary sutures between the
skin of the flap and the underlying muscle or fascia to prevent
shearing of the musculocutaneous perforating vessels. Other
techniques include avoidance of skeletonizing the vascular
pedicle unless absolutely necessary to avoid spasm and injury.
Lastly, in flaps that are tunneled beneath skin bridges, it is
important to avoid a tourniquet effect produced by the poten­
tially constrictive skin bridge.
Ultimate flap loss can be due to intrinsic or extrinsic
reasons. Flap loss due to intrinsic reasons is largely caused by
inadequate blood supply, which is the most common reason
of flap compromise. Flap compromise due to extrinsic circum­
stances include infection, hypotension, and vasoconstricting
agents such as pressors. Compression or tension on the flap
due to hematoma is another extrinsic cause of flap compro­
mise. Exploration of the flap should be expeditious when
failure is suspected.
Donor site complications include fluid collections due to
dead space (seroma, hematoma), wound separation, infection
and injury to adjacent structures during flap harvest.
Errors in patient management are a common cause of
postoperative complications. For patients undergoing flap
surgery, the most common errors of management include:
(1) inadequate attention to the patient’s underlying medical
conditions; (2) inadequate assessment or management of
intravascular volume status; and (3) inadequate surveillance
of flap viability and perfusion.
The safety and reliability of muscle and musculocutaneous
flaps has been repeatedly demonstrated. Such successes now
encourage surgeons to choose a more complex procedure than
a simple one, especially if form and function can be improved.
For example, in the reconstruction of a defect involving the
lower leg, the soleus and gastrocnemius provide reliable and
safe closure. However, the aesthetic and functional results
may be unacceptable to certain patients. In these patients, a
more sophisticated technique such as perforator-based pro­
peller flaps, and perforator flaps with microsurgery approach
may be appropriate and become the procedure of choice
according to the reconstructive elevator concept.
Microvascular tissue transplantation is clearly indicated as
the procedure of choice for certain defects. In fact, the use of
microvascular free tissue transfer to reconstruct head and
neck defects has revolutionized the field and has allowed both
functional and aesthetically pleasing results for large extirpa­
tive defects. The term “microsurgery” has evolved to the
concept of supermicrosurgery and the variety and concept of
flaps are evolving from musculocutaneous to perforator flaps.
Although the complexity of reconstruction and the approach
are continuously evolving, the basic principle of flap selection
and application remains the same: The quality of the result is
far greater than the risk involved.
16. Mathes SJ, Nahai F. Classification of the vascular anatomy of
muscles: experimental and clinical correlation. Plast Reconstr Surg.
1981;67:177–187. The muscle flap vascularization classification scheme
is described based on the anatomy of the vasculature. It plays a vital role
in elevating the muscle flaps.
25. Gottlieb LJ, Krieger LM. From the reconstructive ladder to the
reconstructive elevator. Plast Reconstr Surg. 1994;93:1503–1504. The
reconstruction in the modern age should be focused to address the issues
of function and cosmetics to achieve the overall best result in an optimal
way.
33. Taylor GI, Palmer JH. The vascular territories (angiosomes) of the
body: experimental study and clinical applications. Br J Plast Surg.
1987;40:113–141. Cadaveric dissections were performed to characterize
cutaneous blood supply. The angiosome concept is described.
39. Hallock GG. The complete classification of flaps. Microsurgery.
2004;24:157–161. The six Cs in addition to circulation included
Access the complete reference list online at

432
CHAPTER 22 • Flap classification and applications
constituents (composition), conformation (form/shape), contiguity
(destination), construction (type of pedicle), and conditioning
(preparation). This paper further outlined this classification in
accordance with the six Cs and named it “complete classification
of flaps”.
40. Cormack GC, Lamberty BG. A classification of fascio-cutaneous
flaps according to their patterns of vascularisation. Br J Plast Surg.
1984;37:80–87.
41. Hallock GG. Simplified nomenclature for compound flaps. Plast
Reconstr Surg. 2000;105:1465–1470, quiz 71–72.
57. Blondeel PN, Van Landuyt KH, Monstrey SJ, et al. The “Gent”
consensus on perforator flap terminology: preliminary definitions.
Plast Reconstr Surg. 2003;112:1378–1383, quiz 83, 516; discussion
84–87.
60. Pignatti M, Ogawa R, Hallock GG, et al. The “Tokyo” consensus
on propeller flaps. Plast Reconstr Surg. 2011;127:716–722.
69. Hong JP. The use of supermicrosurgery in lower extremity
reconstruction: the next step in evolution. Plast Reconstr Surg.
2009;123:230–235.
187. Wei FC, Mardini S. Free-style free flaps. Plast Reconstr Surg.
2004;114:910–916. In contrast to elevating a flap on a previously
identified perforator, the skin island can be selected first and the
appropriate perforator located on the flap can be selected in a sequence.
This is the core of the free-style approach and allows the surgeon to
efficiently handle unexpected events occurring during flap harvest or in
cases with anatomical variations.
267. Ramirez OM, Ruas E, Dellon AL. “Components separation”
method for closure of abdominal wall defects: an anatomical and
clinical study. Plast Reconstr Surg. 1990;86:519–526. Loss of abdominal
domain is a common surgical problem. The anatomical basis and
technical details of the now-ubiquitous components separation are
described.

432.e1
References
References
1. Bhishagratna KK. An English translation of the Sushruta Samhita
based on original Sanskrit text. Calcutta: Bose; 1916.
2. Pearl RM, Johnson D. The vascular supply to the skin: an
anatomical and physiological reappraisal–Part II. Ann Plast Surg.
1983;11:196–205.
3. Tagliacozzi G De curtorum chirurgia per institione. Venice; 1597.
4. Carpue JC. An Account of Two Successful Operations for Restoring a
Lost Nose from the Integuments of the Forehead. London: Longman;
1816.
5. Von Graefe CF. Rhinoplastik, oder die kunst den verlust der nase
organisch zu ersetzen. Berlin: Realschulbuchhandlung; 1818.
6. Manchot C. Die hautarterien des menschlichen korpers. Vogel: Leipzig;
1889.
7. Tansini I. Sporo il mio nuova processo di amputazione della
mammella. Gazz Med Ital. 1906;57:141.
8. Davis JS. Plastic Surgery: Its Principles and Practices. Philadelphia:
Blakiston; 1919.
9. McGregor IA. The temporal flap in intra-oral cancer: its use in
repairing the post-excisional defect. Br J Plast Surg.
1963;16:318–335.
10. Bakamjian VY. A technique for primary reconstruction of the
palate after radical maxillectomy for cancer. Plast Reconstr Surg.
1963;31:103–117.
11. Stark WJ. The use of pedicled muscle flaps in the treatment of
chronic osteomyelitis resulting from compound fractures. J Bone
Joint Surg. 1946;28:343–350.
12. Ger R. The technique of muscle transposition in the operative
treatment of traumatic and ulcerative lesions of the leg. J Trauma.
1971;11:502–510.
13. Orticochea M. History of the discovery of the musculocutaneous
flap method as a substitute for the delay method. Ann Plast Surg.
1983;11:63–68.
14. McCraw JB, Dibbell DG, Carraway JH. Clinical definition of
independent myocutaneous vascular territories. Plast Reconstr
Surg. 1977;60:341–352.
15. Mathes SJ, McCraw JB, Vasconez LO. Muscle transposition flaps
for coverage of lower extremity defects: anatomic considerations.
Surg Clin North Am. 1974;54:1337–1354.
16. Mathes SJ, Nahai F. Classification of the vascular anatomy of
muscles: experimental and clinical correlation. Plast Reconstr Surg.
1981;67:177–187. The muscle flap vascularization classification scheme
is described based on the anatomy of the vasculature. It plays a vital role
in elevating the muscle flaps.
17. Schneider WJL, Brown RG. Latissimus dorsi myocutaneous flaps
for breast reconstruction. Br J Plast Surg. 1977;30:277–281.
18. Brown RG, Fleming WH, Jurkiewicz MJ. An island flap of the
pectoralis major muscle. Br J Plast Surg. 1977;30:161–165.
19. Vasconez LO, Bostwick J 3rd, McCraw J. Coverage of exposed
bone by muscle transposition and skin grafting. Plast Reconstr
Surg. 1974;53:526–530.
20. Ariyan S. One-stage reconstruction for defects of the mouth using
a sternomastoid myocutaneous flap. Plast Reconstr Surg.
1979;63:618–625.
21. Ariyan S. The pectoralis major myocutaneous flap. A versatile flap
for reconstruction in the head and neck. Plast Reconstr Surg.
1979;63:73–81.
22. Mathes SJ, Vasconez LO. Myocutaneous free-flap transfer.
Anatomical and experimental considerations. Plast Reconstr Surg.
1978;62:162–166.
23. Ponten B. The fasciocutaneous flap: its use in soft tissue defects of
the lower leg. Br J Plast Surg. 1981;34:215–220.
24. Mathes SJNF. Clinical Applications for Muscle and Musculocutaneous
Flaps. St. Louis: CV Mosby; 1982.
25. Gottlieb LJ, Krieger LM. From the reconstructive ladder
to the reconstructive elevator. Plast Reconstr Surg. 1994;93:
1503–1504. The reconstruction in the modern age should be focused to
address the issues of function and cosmetics to achieve the overall best
result in an optimal way.
26. Mathes SJNF. Reconstructive Surgery: Principles, Anatomy &
Technique. New York: Churchill Livingstone; 1997.
27. Mardini S, Tsai FC, Wei FC. The thigh as a model for free style free
flaps. Clin Plast Surg. 2003;30:473–480.
28. Tolhurst DE. A comprehensive classification of flaps: the atomic
system. Plast Reconstr Surg. 1987;80:608–609.
29. Cormack GCLB. The Arterial Anatomy of Skin Flaps. 2nd ed.
Edinburgh: Churchill Livingstone; 1994.
30. Milton SH. Pedicled skin-flaps–the fallacy of the length: width
ratio. Br J Surg. 1969;56:381.
31. Milton SH. The effects of “delay” on the survival of experimental
pedicled skin flaps. Br J Plast Surg. 1969;22:244–252.
32. Behan FC. The keystone design perforator island flap in
reconstructive surgery. ANZ J Surg. 2003;73:112–120.
33. Taylor GI, Palmer JH. The vascular territories (angiosomes) of the
body: experimental study and clinical applications. Br J Plast Surg.
1987;40:113–141. Cadaveric dissections were performed to characterize
cutaneous blood supply. The angiosome concept is described.
34. Salmon M. The Arteries of the Skin. London: Churchill Livingston;
1988.
35. Morris SF, Taylor GI. Predicting the survival of experimental skin
flaps with a knowledge of the vascular architecture. Plast Reconstr
Surg. 1993;92:1352–1361.
36. Tang M, Yin Z, Morris SF. A pilot study on three-dimensional
visualization of perforator flaps by using angiography in cadavers.
Plast Reconstr Surg. 2008;122:429–437.
37. Nakajima H, Fujino T, Adachi S. A new concept of vascular supply
to the skin and classification of skin flaps according to their
vascularization. Ann Plast Surg. 1986;16:1–19.
38. Saint-Cyr M, Wong C, Schaverien M, et al. The perforasome
theory: vascular anatomy and clinical implications. Plast Reconstr
Surg. 2009;124:1529–1544.
39. Hallock GG. The complete classification of flaps. Microsurgery.
2004;24:157–161. The six Cs in addition to circulation included
constituents (composition), conformation (form/shape), contiguity
(destination), construction (type of pedicle), and conditioning
(preparation). This paper further outlined this classification in accordance
with the six Cs and named it “complete classification of flaps”.
40. Cormack GC, Lamberty BG. A classification of fascio-cutaneous
flaps according to their patterns of vascularisation. Br J Plast Surg.
1984;37:80–87.
41. Hallock GG. Simplified nomenclature for compound flaps. Plast
Reconstr Surg. 2000;105:1465–1470, quiz 71–72.
42. Hallock GG. Further clarification of the nomenclature for
compound flaps. Plast Reconstr Surg. 2006;117:151e–160e.
43. Tobin GR. Pectoralis major segmental anatomy and segmentally
split pectoralis major flaps. Plast Reconstr Surg. 1985;75:814–824.
44. Tobin GR. Segmentally split pectoral girdle muscle flaps for
chest-wall and intrathoracic reconstruction. Clin Plast Surg.
1990;17:683–696.
45. Morain WD, Colen LB, Hutchings JC. The segmental pectoralis
major muscle flap: a function-preserving procedure. Plast Reconstr
Surg. 1985;75:825–830.
46. Manktelow RT, Zuker RM. Muscle transplantation by fascicular
territory. Plast Reconstr Surg. 1984;73:751–757.
47. Chang N, Mathes SJ. Comparison of the effect of bacterial
inoculation in musculocutaneous and random-pattern flaps. Plast
Reconstr Surg. 1982;70:1–10.
48. Mathes SJ, Nahai F. Muscle flap transposition with function
preservation: technical and clinical considerations. Plast Reconstr
Surg. 1980;66:242–249.
49. Parry SW, Mathes SJ. Bilateral gluteus maximus myocutaneous
advancement flaps: sacral coverage for ambulatory patients. Ann
Plast Surg. 1982;8:443–445.
50. Schafer K. The subcutaneous vascular system (lower extremity):
studies on micro-preparations. Gegenbaurs Morphol Jahrb.
1975;121:492–514.

432.e2
CHAPTER 22 • Flap classification and applications
51. McGregor IA, Morgan G. Axial and random pattern flaps. Br J
Plast Surg. 1973;26:202–213.
52. Wei FC, Jain V, Suominen S, Chen HC. Confusion among
perforator flaps: what is a true perforator flap? Plast Reconstr Surg.
2001;107:874–876.
53. Koshima I, Soeda S. Inferior epigastric artery skin flaps without
rectus abdominis muscle. Br J Plast Surg. 1989;42:645–648.
54. Hallock GG. Direct and indirect perforator flaps: the history and
the controversy. Plast Reconstr Surg. 2003;111:855–865, quiz 66.
55. Allen RJ, Treece P. Deep inferior epigastric perforator flap for
breast reconstruction. Ann Plast Surg. 1994;32:32–38.
56. Blondeel PN. One hundred free DIEP flap breast reconstructions: a
personal experience. Br J Plast Surg. 1999;52:104–111.
57. Blondeel PN, Van Landuyt KH, Monstrey SJ, et al. The “Gent”
consensus on perforator flap terminology: preliminary definitions.
Plast Reconstr Surg. 2003;112:1378–1383, quiz 83, 516; discussion
84–87.
58. Blondeel M, Hallock GG, Neligan PC. Perforator Flaps. 2nd ed. St.
Louis: QMP; 2013.
59. Hyakusoku H, Ogawa R, Oki K, Ishii N. The perforator pedicled
propeller (PPP) flap method: report of two cases. J Nippon Med Sch.
2007;74:367–371.
60. Pignatti M, Ogawa R, Hallock GG, et al. The “Tokyo” consensus
on propeller flaps. Plast Reconstr Surg. 2011;127:716–722.
61. Geddes CR, Morris SF, Neligan PC. Perforator flaps: evolution,
classification, and applications. Ann Plast Surg. 2003;50:90–99.
62. Hamdi M, Weiler-Mithoff EM, Webster MH. Deep inferior
epigastric perforator flap in breast reconstruction: experience with
the first 50 flaps. Plast Reconstr Surg. 1999;103:86–95.
63. Higgins JP, Orlando GS, Blondeel PN. Ischial pressure sore
reconstruction using an inferior gluteal artery perforator (IGAP)
flap. Br J Plast Surg. 2002;55:83–85.
64. Blondeel N, Vanderstraeten GG, Monstrey SJ, et al. The donor site
morbidity of free DIEP flaps and free TRAM flaps for breast
reconstruction. Br J Plast Surg. 1997;50:322–330.
65. Hong JP, Sun SH, Ben-Nakhi M. Modified superficial circumflex
iliac artery perforator flap and supermicrosurgery technique for
lower extremity reconstruction: a new approach for moderate-
sized defects. Ann Plast Surg. 2013;71:380–383.
66. Hallock GG. Anatomic basis of the gastrocnemius perforator-based
flap. Ann Plast Surg. 2001;47:517–522.
67. Wei FC, Jain V, Celik N, et al. Have we found an ideal soft-tissue
flap? An experience with 672 anterolateral thigh flaps. Plast
Reconstr Surg. 2002;109:2219–2226, discussion 27–30.
68. Wallace CG, Kao HK, Jeng SF, Wei FC. Free-style flaps: a further
step forward for perforator flap surgery. Plast Reconstr Surg.
2009;124:e419–e426.
69. Hong JP. The use of supermicrosurgery in lower extremity
reconstruction: the next step in evolution. Plast Reconstr Surg.
2009;123:230–235.
70. Koshima I, Yamamoto T, Narushima M, et al. Perforator flaps and
supermicrosurgery. Clin Plast Surg. 2010;37(4):683–689, vii–iii.
71. Hong JP, Koshima I. Using perforators as recipient vessels
(supermicrosurgery) for free flap reconstruction of the knee region.
Ann Plast Surg. 2010;64:291–293.
72. Buyukunal SN, Cerrah A, Dervisoglu S. Appendix interposition in
the treatment of severe posterior urethral injuries. J Urol.
1995;154(2 Pt 2):840–843.
73. Koshima I, Inagawa K, Okuyama N, Moriguchi T. Free
vascularized appendix transfer for reconstruction of penile
urethras with severe fibrosis. Plast Reconstr Surg. 1999;103:
964–969.
74. Chen SH, Yeong EK, Tang YB, Chen HC. Free and pedicled
appendix transfer for various reconstructive procedures. Ann Plast
Surg. 2012;69:602–606.
75. Zhang QX, Magovern CJ, Mack CA, et al. Vascular endothelial
growth factor is the major angiogenic factor in omentum:
mechanism of the omentum-mediated angiogenesis. J Surg Res.
1997;67:147–154.
76. Liebermann DM, Kaufmann M. Utilization of the greater
omentum in surgery: a historical review. Neth J Surg.
1991;43:136–144.
77. Bikfalvi A, Alterio J, Inyang AL, et al. Basic fibroblast growth
factor expression in human omental microvascular endothelial
cells and the effect of phorbol ester. J Cell Physiol. 1990;144:
151–158.
78. Hultman CS, Carlson GW, Losken A, et al. Utility of the omentum
in the reconstruction of complex extraperitoneal wounds and
defects: donor-site complications in 135 patients from 1975 to 2000.
Ann Surg. 2002;235:782–795.
79. Hultman CS, Culbertson JH, Jones GE, et al. Thoracic
reconstruction with the omentum: indications, complications, and
results. Ann Plast Surg. 2001;46:242–249.
80. Corral CJ, Prystowsky JB, Weidrich TA, Harris GD. Laparoscopic-
assisted bipedicle omental flap mobilization for reconstruction of a
chest wall defect. J Laparoendosc Surg. 1994;4:343–346.
81. Domene CE, Volpe P, Onari P, et al. Omental flap obtained by
laparoscopic surgery for reconstruction of the chest wall. Surg
Laparosc Endosc. 1998;8:215–218.
82. McCarthy JG, Cutting CB, Shaw WW. Vascularized calvarial flaps.
Clin Plast Surg. 1987;14:37–47.
83. Casanova R, Cavalcante D, Grotting JC, et al. Anatomic basis for
vascularized outer-table calvarial bone flaps. Plast Reconstr Surg.
1986;78:300–308.
84. Cutting CB, McCarthy JG, Berenstein A. Blood supply of the upper
craniofacial skeleton: the search for composite calvarial bone flaps.
Plast Reconstr Surg. 1984;74:603–610.
85. Lee HB, Hong JP, Kim KT, et al. Orbital floor and infraorbital rim
reconstruction after total maxillectomy using a vascularized
calvarial bone flap. Plast Reconstr Surg. 1999;104:646–653.
86. Sakai K, Doi K, Kawai S. Free vascularized thin corticoperiosteal
graft. Plast Reconstr Surg. 1991;87:290–298.
87. Giessler GA, Schmidt AB. Thumb salvage with skin grafted medial
femoral corticoperiosteal free flap. J Plast Reconstr Aesthet Surg.
2011;64:1693–1696.
88. Iorio ML, Masden DL, Higgins JP. Cutaneous angiosome territory
of the medial femoral condyle osteocutaneous flap. J Hand Surg.
2012;37:1033–1041.
89. Wong VW, Higgins JP, Katz RD. Functional reconstruction
of subtotal thumb metacarpal defect with a vascularized
medial femoral condyle flap: case report. J Hand Surg.
2014;39:2005–2008.
90. Hubert DM, Low DW, Serletti JM, et al. Fibula free flap
reconstruction of the pelvis in children after limb-sparing internal
hemipelvectomy for bone sarcoma. Plast Reconstr Surg.
2010;125:195–200.
91. Innocenti M, Ceruso M, Manfrini M, et al. Free vascularized
growth-plate transfer after bone tumor resection in children.
J Reconstr Microsurg. 1998;14:137–143.
92. Erdmann D, Garcia RM, Blueschke G, et al. Vascularized fibula-
based physis transfer for pediatric proximal humerus
reconstruction. Plast Reconstr Surg. 2013;132:281e–287e.
93. Breidenbach WC, Terzis JK. The blood supply of vascularized
nerve grafts. J Reconstr Microsurg. 1986;3:43–58.
94. Breidenbach W, Terzis JK. The anatomy of free vascularized nerve
grafts. Clin Plast Surg. 1984;11:65–71.
95. Taylor GI, Ham FJ. The free vascularized nerve graft. A further
experimental and clinical application of microvascular techniques.
Plast Reconstr Surg. 1976;57:413–426.
96. Daniel RK, Terzis J, Schwarz G. Neurovascular free flaps. A
preliminary report. Plast Reconstr Surg. 1975;56:13–20.
97. Acland RD, Schusterman M, Godina M, et al. The
saphenous neurovascular free flap. Plast Reconstr Surg.
1981;67:763–774.
98. Gilbert A. Vascularized sural nerve graft. Clin Plast Surg.
1984;11:73–77.
99. Doi K, Kuwata N, Kawakami F, et al. The free vascularized sural
nerve graft. Microsurgery. 1984;5:175–184.

432.e3
References
100. Terzis JK, Kostopoulos VK. Vascularized nerve grafts for lower
extremity nerve reconstruction. Ann Plast Surg. 2010;64:169–176.
101. Terzis JK, Kostopoulos VK. Vascularized ulnar nerve graft: 151
reconstructions for posttraumatic brachial plexus palsy. Plast
Reconstr Surg. 2009;123:1276–1291.
102. Terzis JK, Skoulis TG, Soucacos PN. Vascularized nerve grafts. A
review. Int Angiol. 1995;14:264–277.
103. Lin CH, Ali R, Chen SC, Wallace C, et al. Vascularized groin
lymph node transfer using the wrist as a recipient site for
management of postmastectomy upper extremity lymphedema.
Plast Reconstr Surg. 2009;123:1265–1275.
104. Cheng MH, Chen SC, Henry SL, et al. Vascularized groin lymph
node flap transfer for postmastectomy upper limb lymphedema:
flap anatomy, recipient sites, and outcomes. Plast Reconstr Surg.
2013;131:1286–1298.
105. Althubaiti GA, Crosby MA, Chang DW. Vascularized
supraclavicular lymph node transfer for lower extremity
lymphedema treatment. Plast Reconstr Surg. 2013;131:133e–135e.
106. Cheng MH, Huang JJ, Wu CW, et al. The mechanism of
vascularized lymph node transfer for lymphedema: natural
lymphaticovenous drainage. Plast Reconstr Surg.
2014;133:192e–198e.
107. Ito R, Suami H. Overview of lymph node transfer for lymphedema
treatment. Plast Reconstr Surg. 2014;134:548–556.
108. Bostwick J, Briedis J, Jurkiewicz MJ. The reverse flow temporal
artery island flap. Clin Plast Surg. 1976;3:441–445.
109. Gillies HD, Millard DR. Principles and Art of Plastic Surgery. Boston:
Little Brown; 1957.
110. Matthews RN, Fatah F, Davies DM, et al. Experience with the
radial forearm flap in 14 cases. Scand J Plast Reconstr Surg.
1984;18:303–310.
111. Angrigiani C, Grilli D, Dominikow D, Zancolli EA. Posterior
interosseous reverse forearm flap: experience with 80 consecutive
cases. Plast Reconstr Surg. 1993;92:285–293.
112. Dautel G, Merle M. Dorsal metacarpal reverse flaps. Anatomical
basis and clinical application. J Hand Surg [Br]. 1991;16:400–405.
113. Almeida MF, da Costa PR, Okawa RY. Reverse-flow island sural
flap. Plast Reconstr Surg. 2002;109:583–591.
114. Orgill DP, Pribaz JJ. Reverse peroneal flaps: two surgical
approaches. Ann Plast Surg. 1994;33:17–22.
115. Ishikawa K, Isshiki N, Hoshino K, Mori C. Distally based lateral
calcaneal flap. Ann Plast Surg. 1990;24:10–16.
116. Hasegawa M, Torii S, Katoh H, Esaki S. The distally based
superficial sural artery flap. Plast Reconstr Surg. 1994;93:1012–1020.
117. de Blacam C, Colakoglu S, Ogunleye AA, et al. Risk factors
associated with complications in lower-extremity reconstruction
with the distally based sural flap: a systematic review and pooled
analysis. J Plast Reconstr Aesthet Surg. 2014;67:607–616.
118. Semple JL. Retrograde microvascular augmentation
(turbocharging) of a single-pedicle TRAM flap through a deep
inferior epigastric arterial and venous loop. Plast Reconstr Surg.
1994;93:109–117.
119. Takayanagi S, Ohtsuka M. Extended transverse rectus abdominis
musculocutaneous flap. Plast Reconstr Surg. 1989;83:1057–1060.
120. Harashina T, Sone K, Inoue T, et al. Augmentation of circulation of
pedicled transverse rectus abdominis musculocutaneous flaps by
microvascular surgery. Br J Plast Surg. 1987;40:367–370.
121. Yamamoto Y, Nohira K, Shintomi Y, et al. Turbo charging” the
vertical rectus abdominis myocutaneous (turbo-VRAM) flap for
reconstruction of extensive chest wall defects. Br J Plast Surg.
1994;47:103–107.
122. Nakayama Y, Soeda S, Kasai Y. Flaps nourished by arterial inflow
through the venous system: an experimental investigation. Plast
Reconstr Surg. 1981;67:328–334.
123. Yan H, Zhang F, Akdemir O, et al. Clinical applications of venous
flaps in the reconstruction of hands and fingers. Arch Orthop
Trauma Surg. 2011;131:65–74.
124. Yan H, Fan C, Zhang F, et al. Reconstruction of large dorsal digital
defects with arterialized venous flaps: our experience and
comprehensive review of literature. Ann Plast Surg.
2013;70:666–671.
125. Woo SH, Kim KC, Lee GJ, et al. A retrospective analysis of 154
arterialized venous flaps for hand reconstruction: an 11-year
experience. Plast Reconstr Surg. 2007;119:1823–1838.
126. Yan H, Brooks D, Ladner R, et al. Arterialized venous flaps: a
review of the literature. Microsurgery. 2010;30:472–478.
127. Thatte MR, Thatte RL. Venous flaps. Plast Reconstr Surg.
1993;91:747–751.
128. Chen HC, Tang YB, Noordhoff MS. Four types of venous flaps
for wound coverage: a clinical appraisal. J Trauma. 1991;31:
1286–1293.
129. Chang XZ, Yin J, Sun J, et al. A retrospective study of different
local treatments in breast cancer patients with synchronous
ipsilateral supraclavicular lymph node metastasis. J Cancer Res
Therapeutics. 2013;9(suppl):S158–S161.
130. Chen SC, Chang HK, Lin YC, et al. Prognosis of breast cancer after
supraclavicular lymph node metastasis: not a distant metastasis.
Ann Surg Oncol. 2006;13:1457–1465.
131. Guba AM Jr. Study of the delay phenomenon in axial pattern flaps
in pigs. Plast Reconstr Surg. 1979;63:550–554.
132. Banbury J, Siemionow M, Porvasnik S, et al. Muscle flaps’
triphasic microcirculatory response to sympathectomy and
denervation. Plast Reconstr Surg. 1999;104:730–737.
133. Neumann CG. The expansion of an area of skin by progressive
distention of a subcutaneous balloon; use of the method for
securing skin for subtotal reconstruction of the ear. Plast Reconstr
Surg (1946). 1957;19:124–130.
134. Radovan C. Adjacent flap development using expandable silastic
implant. Annual ASPRS meeting. Boston, 1976.
135. Casanova D, Bali D, Bardot J, et al. Tissue expansion of the lower
limb: complications in a cohort of 103 cases. Br J Plast Surg.
2001;54:310–316.
136. Pribaz JJ, Fine NA. Prelamination: defining the prefabricated
flap–a case report and review. Microsurgery. 1994;15:618–623.
137. Pribaz JJ, Weiss DD, Mulliken JB, Eriksson E. Prelaminated free
flap reconstruction of complex central facial defects. Plast Reconstr
Surg. 1999;104:357–365, discussion 66–67.
138. Khouri RK, Upton J, Shaw WW. Principles of flap prefabrication.
Clin Plast Surg. 1992;19:763–771.
139. Cicconetti A, Matteini C, Cruccu G, Romaniello A. Comparative
study on sensory recovery after oral cavity reconstruction by free
flaps: preliminary results. J Craniomaxillofac Surg. 2000;28:74–78.
140. Kuriakose MA, Loree TR, Spies A, et al. Sensate radial forearm
free flaps in tongue reconstruction. Arch Otolaryngol Head Neck
Surg. 2001;127:1463–1466.
141. Kimata Y, Uchiyama K, Ebihara S, et al. Comparison of innervated
and noninnervated free flaps in oral reconstruction. Plast Reconstr
Surg. 1999;104:1307–1313.
142. Harris PG, Letrosne E, Caouette-Laberge L, Egerszegi EP.
Long-term follow-up of coverage of weight bearing surface of the
foot with free muscular flap in a pediatric population.
Microsurgery. 1994;15:424–429.
143. Chen SL, Chen TM, Chou TD, et al. The distally based lesser
saphenous venofasciocutaneous flap for ankle and heel
reconstruction. Plast Reconstr Surg. 2002;110:1664–1672.
144. Santanelli F, Tenna S, Pace A, Scuderi N. Free flap reconstruction
of the sole of the foot with or without sensory nerve coaptation.
Plast Reconstr Surg. 2002;109:2314–2322, discussion 23–24.
145. Hong JP, Kim EK. Sole reconstruction using anterolateral thigh
perforator free flaps. Plast Reconstr Surg. 2007;119:186–193.
146. Hallock GG. Simultaneous transposition of anterior thigh muscle
and fascia flaps: an introduction to the chimera flap principle. Ann
Plast Surg. 1991;27:126–131.
147. Belousov AE, Kishemasov SD, Kochish AY, Pinchuk VD. A new
classification of vascularized flaps in plastic and reconstructive
surgery. Ann Plast Surg. 1993;31:47–52, discussion 52–3.
148. Roehl KR, Mahabir RC. A practical guide to free tissue transfer.
Plast Reconstr Surg. 2013;132:147e–158e.

432.e4
CHAPTER 22 • Flap classification and applications
149. Pluvy I, Panouilleres M, Garrido I, et al. Smoking and plastic
surgery, part II. Clinical implications: a systematic review with
meta-analysis. Ann Chir Plast Esthet. 2015;60:e15–e49.
150. Fischer JP, Nelson JA, Sieber B, et al. Free tissue transfer in the
obese patient: an outcome and cost analysis in 1258 consecutive
abdominally based reconstructions. Plast Reconstr Surg.
2013;131:681e–692e.
151. Suominen S, Asko-Seljavaara S. Free flap failures. Microsurgery.
1995;16:396–399.
152. Davison SP, Kessler CM, Al-Attar A. Microvascular free flap failure
caused by unrecognized hypercoagulability. Plast Reconstr Surg.
2009;124:490–495.
153. Khouri RK, Cooley BC, Kunselman AR, et al. A prospective study
of microvascular free-flap surgery and outcome. Plast Reconstr
Surg. 1998;102:711–721.
154. Endara M, Masden D, Goldstein J, et al. The role of chronic and
perioperative glucose management in high-risk surgical closures: a
case for tighter glycemic control. Plast Reconstr Surg.
2013;132:996–1004.
155. Moran SL, Salgado CJ, Serletti JM. Free tissue transfer in patients
with renal disease. Plast Reconstr Surg. 2004;113:2006–2011.
156. Moran SL, Illig KA, Green RM, Serletti JM. Free-tissue transfer in
patients with peripheral vascular disease: a 10-year experience.
Plast Reconstr Surg. 2002;109:999–1006.
157. Chen CL, Shore AD, Johns R, et al. The impact of obesity on breast
surgery complications. Plast Reconstr Surg. 2011;128:395e–402e.
158. Genden EM, Rinaldo A, Suarez C, et al. Complications of free flap
transfers for head and neck reconstruction following cancer
resection. Oral Oncol. 2004;40:979–984.
159. Duymaz A, Karabekmez FE, Vrtiska TJ, et al. Free tissue transfer
for lower extremity reconstruction: a study of the role of computed
angiography in the planning of free tissue transfer in the
posttraumatic setting. Plast Reconstr Surg. 2009;124:523–529.
160. Masia J, Larranaga J, Clavero JA, et al. The value of the
multidetector row computed tomography for the preoperative
planning of deep inferior epigastric artery perforator flap: our
experience in 162 cases. Ann Plast Surg. 2008;60:29–36.
161. Reddy V, Stevenson TR. MOC-PS(SM) CME article: lower
extremity reconstruction. Plast Reconstr Surg. 2008;121:1–7.
162. Pratt GF, Rozen WM, Chubb D, et al. Preoperative imaging
for perforator flaps in reconstructive surgery: a systematic
review of the evidence for current techniques. Ann Plast Surg.
2012;69:3–9.
163. Hallock GG. Acoustic Doppler sonography, color duplex
ultrasound, and laser Doppler flowmetry as tools for successful
autologous breast reconstruction. Clin Plast Surg. 2011;38:203–211.
164. Seify H, Jones G, Sigurdson L, et al. Endoscopic harvest of four
muscle flaps: safe and effective techniques. Ann Plast Surg.
2002;48:173–179.
165. Schoeller T, Wechselberger G, Hussl H, et al. Aesthetic
improvements in endoscopic gracilis muscle harvest through a
single transverse incision in the groin crease. Plast Reconstr Surg.
2002;110:218–221.
166. Avital S, Rosin D, Brasesco O, et al. Laparoscopic mobilization of
an omental flap for reconstruction of an infected sternotomy
wound. Ann Plast Surg. 2002;49:307–311.
167. Huang SC, Zhnag Y. All roads lead to Rome: the impact of
multiple attainment means on motivation. J Pers Soc Psychol.
2013;104:236–248.
168. Webb TL, Sheeran P. Mechanisms of implementation intention
effects: the role of goal intentions, self-efficacy, and accessibility of
plan components. Br J Soc Psychol. 2008;47:373–395.
169. Hong JP, Yim JH, Malzone G, et al. The thin gluteal artery
perforator free flap to resurface the posterior aspect of the leg and
foot. Plast Reconstr Surg. 2014;133:1184–1191.
170. Hong JP, Shin HW, Kim JJ, et al. The use of anterolateral thigh
perforator flaps in chronic osteomyelitis of the lower extremity.
Plast Reconstr Surg. 2005;115:142–147.
171. Nenad T, Reiner W, Michael S, et al. Saphenous perforator flap for
reconstructive surgery in the lower leg and the foot: a clinical
study of 50 patients with posttraumatic osteomyelitis. J Trauma.
2010;68:1200–1207.
172. Park G, Kim H. Treatment of chronic osteomyelitis using the
medial sural perforator flap. J Plast Reconstr Aesthet Surg.
2010;63:153–159.
173. Yazar S, Lin CH, Lin YT, et al. Outcome comparison between free
muscle and free fasciocutaneous flaps for reconstruction of distal
third and ankle traumatic open tibial fractures. Plast Reconstr Surg.
2006;117:2468–2475, discussion 76–77.
174. Tintle SM, Levin LS. The reconstructive microsurgery ladder in
orthopaedics. Injury. 2013;44:376–385.
175. Riaz M, Khan K, Leonard AG. Complications associated with
suction drains after microvascular anastomeses. Microsurgery.
1996;17:51–52.
176. Mathes SJ, Feng LJ, Hunt TK. Coverage of the infected wound.
Ann Surg. 1983;198:420–429.
177. Logan SE, Alpert BS, Buncke HJ. Free serratus anterior muscle
transplantation for hand reconstruction. Br J Plast Surg.
1988;41:639–643.
178. Hui K, Zhang F, Pickus E, et al. Modification of the vertical rectus
abdominis musculocutaneous (VRAM) flap for functional
reconstruction of complex vulvoperineal defects. Ann Plast Surg.
2003;51:556–560.
179. Wong AK, Joanna Nguyen T, Peric M, et al. Analysis of risk factors
associated with microvascular free flap failure using a multi-
institutional database. Microsurgery. 2015;35:6–12.
180. Al-Qattan MM. Latissimus dorsi transfer for external rotation
weakness of the shoulder in obstetric brachial plexus palsy. J Hand
Surg [Br]. 2003;28:487–490.
181. Ninkovic M, Stenzl A, Schwabegger A, et al. Free neurovascular
transfer of latisstmus dorsi muscle for the treatment of
bladder acontractility: II. Clinical results. J Urol. 2003;169:
1379–1383.
182. Shapiro MJ. Use of trapezius myocutaneous flaps in the
reconstruction of head and neck defects. Arch Otolaryngol.
1981;107:333–336.
183. Cuono CB, Ariyan S. Immediate reconstruction of a composite
mandibular defect with a regional osteomusculocutaneous flap.
Plast Reconstr Surg. 1980;65:477–484.
184. Pikani J, Ulla A, Tuulik E. Clinical evaluation of the pectoralis
major flap for reconstruction in head and neck cancer. Scand J Plast
Reconstr Surg Hand Surg. 1994;28:217–223.
185. Koshima I, Hosoda M, Ohta S, et al. Free vascularized iliac
osteomusculocutaneous flaps based on the lateral circumflex
femoral system for repair of large mandibular defects. Ann Plast
Surg. 1994;33:581–588.
186. Hardin JC Jr. Reconstruction of maxilla with free latissimus
dorsi-scapular osteomusculocutaneous flap. Plast Reconstr Surg.
2003;111:965, author reply 965–966.
187. Wei FC, Mardini S. Free-style free flaps. Plast Reconstr Surg.
2004;114:910–916. In contrast to elevating a flap on a previously
identified perforator, the skin island can be selected first and the
appropriate perforator located on the flap can be selected in a sequence.
This is the core of the free-style approach and allows the surgeon to
efficiently handle unexpected events occurring during flap harvest or in
cases with anatomical variations.
188. Oh TS, Hallock G, Hong JP. Freestyle propeller flaps to reconstruct
defects of the posterior trunk: a simple approach to a difficult
problem. Ann Plast Surg. 2012;68:79–82.
189. Hallock GG. Is there a “learning curve” for muscle perforator
flaps? Ann Plast Surg. 2008;60:146–149.
190. Owens N. A compound neck pedicle designed for the repair of
massive facial defects: formation, development, and application.
Plast Reconstr Surg. 1955;15:369–389.
191. Littlewood M. Compound skin and sternomastoid flaps for repair
in extensive carcinoma of the head and neck. Br J Plast Surg.
1967;20:403–419.
192. Conley J. Use of composite flaps containing bone for
major repairs in the head and neck. Plast Reconstr Surg.
1972;49:522–526.

432.e5
References
193. Larson DL, Goepfert H. Limitations of the sternocleidomastoid
musculocutaneous flap in head and neck cancer reconstruction.
Plast Reconstr Surg. 1982;70:328–335.
194. Gersuny R. Plastischer ersatz der mangenscheimhunt. Zentralbl
Chir. 1887;14:706.
195. Hueston JT, McConchie HA. A compound pectoral flap. Aust N Z J
Surg. 1968;38:61–63.
196. Maruyama Y, Nakajima H, Fujino T. A dynamic reconstruction of a
facial defect with a pectoralis major myocutaneous flap. Br J Plast
Surg. 1980;33:145–149.
197. Withers EH, Franklin JD, Madden JJ, et al. Immediate
reconstruction of the pharynx and cervical esophagus
with the pectoralis major myocutaneous flap following
laryngopharyngectomy. Plast Reconstr Surg. 1981;8:
898–904.
198. Ariyan S. The pectoralis major muscle for single-stage
reconstruction of the difficult wounds of the orbit and
pharyngoesophagus. Plast Reconstr Surg. 1983;72:468–477.
199. Morgan RF, Sargent LA, Hoopes JE. Midfacial and total nasal
reconstruction with bilateral pectoralis major myocutaneous flaps.
Plast Reconstr Surg. 1984;73:824–826.
200. Lam KH, Wei WI, Siu KF. The pectoralis major costomyocutaneous
flap for mandibular reconstruction. Plast Reconstr Surg.
1984;73:904–910.
201. Mathes SJ, Nahai F. Clinical Atlas of Mmuscle and Musculocutaneous
Flaps. St. Louis: CV Mosby; 1979.
202. Haas F, Weiglein A, Schwarzl F, et al. The lower trapezius
musculocutaneous flap from pedicled to free flap: anatomical basis
and clinical applications based on the dorsal scapular artery. Plast
Reconstr Surg. 2004;113:1580–1590.
203. Lynch JR, Hansen JE, Chaffoo R, et al. The lower trapezius
musculocutaneous flap revisited: versatile coverage for
complicated wounds to the posterior cervical and occipital regions
based on the deep branch of the transverse cervical artery. Plast
Reconstr Surg. 2002;109:444–450.
204. Baek S, Biller HF, Krespi YP, et al. The lower trapezius island
myocutaneous flap. Ann Plast Surg. 1980;5:108–114.
205. Yoshimura Y, Maruyama Y, Takeuchi S. The use of lower trapezius
island flaps in head and neck reconstruction. Br J Plast Surg.
1981;34:334–337.
206. Dufresne C, Cutting C, Valauri F, et al. Reconstruction of
mandibular and floor of mouth defects using the trapezius
osteomyocutaneous flap. Plast Reconstr Surg. 1987;79:687–696.
207. Tansini I. Nuovo processo per I’amputazione della mammilla per
cancre. Riforma Med. 1896;12:3.
208. Quillen CG, Shearin JC, Georgiade NG. Use of the latissimus dorsi
myocutaneous island flap for reconstruction in the head and neck
area. Plast Reconstr Surg. 1978;62:113–117.
209. Barton FE, Spicer TE, Byrd HS. Head and neck reconstruction
with the latissimus dorsi myocutaneous flap: anatomic
observations and report of 60 cases. Plast Reconstr Surg.
1983;71:199–204.
210. Hofer SO, Posch NA, Smit X. The facial artery perforator flap for
reconstruction of perioral defects. Plast Reconstr Surg. 2005;115:996–
1003, discussion 4–5.
211. Kim JT, Kim SK, Koshima I, Moriguchi T. An anatomic study and
clinical applications of the reversed submental perforator-based
island flap. Plast Reconstr Surg. 2002;109:2204–2210.
212. Rahpeyma A, Khajehahmadi S, Razmara F. Submental flap in
intraoral reconstruction after pathologic resections: indications and
limitations. J Maxillofac Oral Surg. 2015;14:57–62.
213. Vural E, Suen JY. The submental island flap in head and neck
reconstruction. Head Neck. 2000;22:572–578.
214. Salgarello M, Seccia A, Eugenio F. Immediate breast reconstruction
with anatomical permanent expandable implants after skin-
sparing mastectomy: aesthetic and technical refinements. Ann Plast
Surg. 2004;52:358–364.
215. Manstein CH, Manstein G, Somers RG, et al. Use of pectoralis
minor muscle in immediate reconstruction of the breast. Plast
Reconstr Surg. 1985;76:566–569.
216. Troilius C. Total muscle coverage of a breast implant is possible
through a transaxillary approach. Plast Reconstr Surg.
1995;95:509–512.
217. Tebbetts JB. Dual plane breast augmentation: optimizing implant-
soft-tissue relationships in a wide range of breast types. Plast
Reconstr Surg. 2001;107:1255–1272.
218. Delay E, Gounot N, Bouillot A. Autologous latissimus breast
reconstruction: a 3-year clinical experience with 100 patients. Plast
Reconstr Surg. 1998;102:1461–1478.
219. Giacalone PL, Bricout N, Dantas MJ, et al. Achieving symmetry in
unilateral breast reconstruction: 17 years experience with 683
patients. Aesthetic Plast Surg. 2002;26:299–302.
220. Chang DW, Youssef A, Cha S, et al. Autologous breast
reconstruction with the extended latissimus dorsi flap. Plast
Reconstr Surg. 2002;110:751–759.
221. Menke H, Erkens M, Olbrisch RR. Evolving concepts in breast
reconstruction with latissimus dorsi flaps: results and follow-up of
121 consecutive patients. Ann Plast Surg. 2001;47:107–114.
222. Mathes SJ, Bostwick J 3rd. A rectus abdominis myocutaneous flap
to reconstruct abdominal wall defects. Br J Plast Surg.
1977;30:282–283.
223. Hartrampf CR, Scheflan M, Black PW. Breast reconstruction with a
transverse abdominal island flap. Plast Reconstr Surg.
1982;69:216–225.
224. Dinner MI, Labandter HP, Dowden RV. The role of the rectus
abdominis myocutaneous flap in breast reconstruction. Plast
Reconstr Surg. 1982;69:209–215.
225. Shestak KC, Fedele GM, Restifo RJ. Treatment of difficult TRAM
flap hernias using intraperitoneal synthetic mesh application. Plast
Reconstr Surg. 2001;107:55–62.
226. Simon AM, Bouwense CL, McMillan S, et al. Comparison of
unipedicled and bipedicled TRAM flap breast reconstructions:
Assessment of physical function and patient satisfaction. Plast
Reconstr Surg. 2004;113:136–140.
227. Dulin WA, Avila RA, Verheyden CN, et al. Evaluation of
abdominal wall strength after TRAM flap surgery. Plast Reconstr
Surg. 2004;113:1662–1665.
228. Hamdi M, Spano A, Van Landuyt K, D’Herde K, Blondeel P,
Monstrey S. The lateral intercostal artery perforators: anatomical
study and clinical application in breast surgery. Plast Reconstr Surg.
2008;121:389–396.
229. Ottino G, De paulis R, Pansini S, et al. Major sternal wound
infection after open heart surgery: a multivariate analysis of risk
factors in 2579 consecutive operative procedures. Ann Thorac Surg.
1987;44:173–179.
230. Jurkiewicz MJ, Bostwick J 3rd, Hester TR, et al. Infected median
sternotomy wound: successful treatment by muscle flap. Ann Surg.
1980;191:738–743.
231. Nahai F, Morales L Jr, Bone DK, et al. Pectoralis major muscle
turnover flaps for closure of the infected sternotomy wound with
preservation of form and function. Plast Reconstr Surg.
1982;70:471–474.
232. Hugo NE, Sultan MR, Ascherman JA, et al. Single-stage
management of 74 consecutive sternal wound complications with
pectoralis major myocutaneous advancement flaps. Plast Reconstr
Surg. 1994;93:1433–1441.
233. Erez E, Katz M, Sharoni E, et al. Pectoralis major muscle flaps for
deep sternal wound infection in neonates. Ann Thorac Surg.
2000;69:572–577.
234. Gursel E, Pummill K, Hakimi M, et al. Pectoralis major muscle
flap for the treatment of mediastinal wound infection in the
pediatric population. Plast Reconstr Surg. 2002;110:844–848.
235. Klesius AA, Dzemali O, Simon A, et al. Successful treatment of
deep sternal infections following open heart surgery by bilateral
pectoralis major flaps. Eur J Cardiothorac Surg. 2004;25:218–223.
236. Clarkson JH, Probst F, Niranjan NS, et al. Our experience using the
vertical rectus abdominis muscle flap for reconstruction in 12
patients with dehiscence of a median sternotomy wound and
mediastinitis. Scand J Plast Reconstr Surg Hand Surg.
2003;37:266–271.

432.e6
CHAPTER 22 • Flap classification and applications
237. Neale HW, Kreilein JG, Schreiber JT, et al. Complete sternectomy
for chronic osteomyelitis with reconstruction using a rectus
abdominis myocutaneous island flap. Ann Plast Surg.
1981;6:305–314.
238. Iacobucci JJ, Stevenson TR, Hall JD, et al. Sternal osteomyelitis:
treatment with rectus abdominis muscle. Br J Plast Surg.
1989;42:452–459.
239. Weinzweig N, Yetman R. Transposition of the greater omentum for
recalcitrant median sternotomy wound infections. Ann Plast Surg.
1995;34:471–477.
240. Moor EV, Neuman RA, Weinberg A, et al. Transposition of the
great omentum for infected sternotomy wounds in cardiac surgery.
Report of 16 cases and review of published reports. Scand J Plast
Reconstr Hand Surg. 1999;33:25–29.
241. Salameh JR, Chock DA, Gonzalez JJ, et al. Laparoscopic harvest of
omental flaps for reconstruction of complex mediastinal wounds.
JSLS. 2003;7:317–322.
242. Fansa H, Handstein S, Schneider W. Treatment of infected median
sternotomy wounds with a myocutaneous latissimus dorsi muscle
flap. Scand Cardiovasc J. 1998;32:33–39.
243. Tizian C, Borst HG, Berger A. Treatment of total sternal necrosis
using the latissimus dorsi muscle flap. Plast Reconstr Surg.
1985;76:703–707.
244. Dejesus RA, Paletta JD, Dabb RW. Reconstruction of the median
sternotomy wound dehiscence using the latissimus dorsi
myocutaneous flap. J Cardiovasc Surg. 2001;42:359–364.
245. Banic A, Ris HB, Erni D, et al. Free latissimus dorsi flap for chest
wall repair after complete resection of infected sternum. Ann
Thorac Surg. 1995;60:1028–1032.
246. Mathes SJ. Chest wall reconstruction. Clin Plast Surg. 1995;
22:187.
247. Deschamps C, Tirnaksiz BM, Darbandi R, et al. Early and
long-term results of prosthetic chest wall reconstruction. J Thorac
Cardiovasc Surg. 1999;117:588–591.
248. Larson DL, McMurtrey MJ. Musculocutaneous flap reconstruction
of chest-wall defects: an experience with 50 patients. Plast Reconstr
Surg. 1984;73:734–740.
249. Scheflan M, Bostwick J 3rd, Nahai F. Chest wall reconstruction-
management of the difficult chest wound. Ann Plast Surg.
1982;8:122–131.
250. Koch H, Tomaselli F, Pierer G, et al. Thoracic wall reconstruction
using both portions of the latissimus dorsi previously divided in
the course of posterolateral thoracotomy. Eur J Cardiothorac Surg.
2002;21:874–878.
251. Bostwick J 3rd, Scheflan M, Nahai F, et al. The “reverse” latissimus
dorsi muscle and musculocutaneous flap: anatomical and clinical
considerations. Plast Reconstr Surg. 1980;65:395–399.
252. McCraw JB, Penix JO, Baker JW. Repair of major defects of the
chest wall and spine with the latissimus dorsi myocutaneous flap.
Plast Reconstr Surg. 1978;62:197–206.
253. Shamberger RC, Welch KJ, Upton J 3rd. Surgical treatment of
thoracic deformity in Poland’s syndrome. J Pediatr Surg.
1989;24:760–765.
254. Arslan E, Unal S, Demirkan F, et al. Poland’s syndrome with rare
deformities: reconstruction with latissimus dorsi muscle through a
single short incision. Scand J Plast Reconstr Surg Hand Surg.
2003;37:304–306.
255. Scheflan M, Mehrhof AI Jr, Ward JD. Meningomyelocele closure
with distally based latissimus dorsi flap. Plast Reconstr Surg.
1984;73:956–959.
256. Ozveren MF, Erol FS, Topsakal C, et al. The significance of the
percentage of the defect size in spina bifida cystica in
determination of the surgical technique. Childs Nerv Syst.
2002;18:614–620.
257. Whetzel TP, Stokes RB, Greenholz SK, et al. Reconstruction of the
toddler diaphragm in severe anterolateral congenital
diaphragmatic hernia with the reverse latissimus dorsi flap. Ann
Plast Surg. 1997;39:615–619.
258. Paletta CE, Huang DB. Intrathoracic application of the reverse
latissimus dorsi muscle flap. Ann Plast Surg. 1999;43:227–231.
259. Vu P, Guedon C, Gehanno P, et al. Anatomic basis of serratus
anterior muscle flap transposition. Surg Radiol Anat.
1988;10:173–185.
260. Arnold PG, Pairolero PC, Waldorf JC. The serratus anterior
muscle: intrathoracic and extrathoracic utilization. Plast Reconstr
Surg. 1984;73:240–248.
261. Miyamoto Y, Hattori T, Niimoto M, et al. Reconstruction of
full-thickness chest wall defects using rectus abdominis
musculocutaneous flap: a report of fifteen cases. Ann Plast Surg.
1986;16:90.
262. Galli A, Raposio E, Santi P. Reconstruction of full-thickness defects
of the thoracic wall by myocutaneous flap transfer: latissimus
dorsi compared with transverse rectus abdominis. Scand J Plast
Reconstr Surg Hand Surg. 1995;29:39–43.
263. Papadopoulos O, Georgiou P, Christopoulos A, et al. Chest wall
reconstruction. Ann Plast Surg. 2002;48:105.
264. Chang RR, Mehrara BJ, Hu Q-Y, et al. Reconstruction of complex
oncologic chest wall defects a 10 year experience. Ann Plast Surg.
2004;52:471–479.
265. Parkash S, Ramakrishnan K. A myocutaneous island flap in the
treatment of a chronic radionecrotic ulcer of the abdominal wall.
Br J Plast Surg. 1980;33:138.
266. Taylor GI, Corlett R, Boyd JB. The extended deep inferior
epigastric flap: a clinical technique. Plast Reconstr Surg.
1983;72:751–765.
267. Ramirez OM, Ruas E, Dellon AL. “Components separation”
method for closure of abdominal wall defects: an anatomical and
clinical study. Plast Reconstr Surg. 1990;86:519–526. Loss of abdominal
domain is a common surgical problem. The anatomical basis and
technical details of the now-ubiquitous components separation are
described.
268. Levine JP, Karp NS. Restoration of abdominal wall integrity as a
salvage procedure in difficult recurrent abdominal wall hernias
using a method of wide myofascial release. Plast Reconstr Surg.
2001;107:707–716.
269. DeFranzo AJ, Kingman GJ, Sterchi JM, et al. Rectus turnover flaps
for the reconstruction of large midline abdominal wall defects.
Ann Plast Surg. 1996;37:18–23.
270. Spear SL, Walker RK. The external oblique flap for
reconstruction of the rectus sheath. Plast Reconstr Surg.
1992;90:608–613.
271. Hershey FB, Butcher HR Jr. Repair of defects after partial resection
of the abdominal wall. Am J Surg. 1964;107:586–590.
272. Hodgkinson DJ, Arnold PG. Chest-wall reconstruction using the
external oblique muscle. Br J Plast Surg. 1980;33:216–220.
273. Moschella F, Cordova A. A new extended external oblique
musculocutaneous flap for reconstruction of large chest-wall
defects. Plast Reconstr Surg. 1999;103:1378–1385.
274. Hobar PC, Rohrich RJ, Byrd HS. Abdominal-wall reconstruction
with expanded musculofascial tissue in a posttraumatic defect.
Plast Reconstr Surg. 1994;94:379–383.
275. Jacobsen WM, Petty PM, Bite U, et al. Massive abdominal-wall
hernia reconstruction with expanded external/internal oblique
and transversalis musculofascia. Plast Reconstr Surg.
1997;100:326–335.
276. Bostwick J 3rd. Latissimus dorsi flap: current applications. Ann
Plast Surg. 1982;9:377–380.
277. Sharma RK, Singh G, Naidu PM. Abdominal wall defects:
anatomic classification and a scheme for management. Ann Plast
Surg. 1998;41:180–184.
278. Brenneman FD, Boulanger BR, Antonyshyn O. Surgical
management of abdominal wall disruption after blunt trauma. J
Trauma. 1995;39:539–544.
279. Sharma RK, Verma GR, Biswas G. Reconstruction of a major
abdominal and chest wall defect using latissimus dorsi and
extended deep inferior epigastric artery flap. Ann Plast Surg.
1992;28:366–369.
280. Kumar P, Varma R. Immediate reconstruction of chest and
abdominal wall defect following high voltage electrical injury.
Burns. 1994;20:557–559.

432.e7
References
281. Olvera-Caballero C, Victoria-Morales G. Neurovascular latissimus
dorsi free-flap transfer for reconstruction of a major abdominal-
wall defect in a 13-month-old child: late follow-up. J Reconstr
Microsurg. 2004;20:237–240.
282. Ninkovic M, Kronberger P, Harpf C, et al. Free innervated
latissimus dorsi muscle flap for reconstruction of full-thickness
abdominal wall defects. Plast Reconstr Surg. 1998;101:971–978.
283. Wangensteen OH. Repair of recurrent and difficult hernias and
other large defects of the abdominal wall employing the iliotibial
tract of fascia lata as a pedicled flap. Surg Gynecol Obstet.
1934;59:766.
284. Nahai F, Hill HL, Hester TR. Experiences with the tensor fascia
lata flap. Plast Reconstr Surg. 1979;63:788–799.
285. Withers EH, Franklin JD, Madden JJ, et al. Further experience with
the tensor fascia lata musculocutaneous flap. Ann Plast Surg.
1980;4:31–36.
286. White DN, Pearl RM, Laub DR, et al. Tensor fascia lata
myocutaneous flap in lower abdominal wall reconstruction. Ann
Plast Surg. 1981;7:155–162.
287. Chevrey PM, Singh NK. Abdominal wall reconstruction with the
free tensor fascia lata musculofasciocutaneous flap using
intraperitoneal gastroepiploic recipient vessels. Ann Plast Surg.
2003;51:97–102.
288. Penington A, Theile D, MacLeod A, et al. Free tensor fasciae latae
flap reconstruction of defects of the chest and abdominal wall:
selection of recipient vessels. Scand J Plast Reconstr Surg Hand Surg.
1996;30:299–305.
289. Ger R, Duboys E. The prevention and repair of large abdominal-
wall defects by muscle transposition: a preliminary
communication. Plast Reconstr Surg. 1983;72:170–178.
290. Wei CY, Chuang DC, Chen HC, et al. The versatility of free rectus
femoris muscle flap: an alternative flap. Microsurgery.
1995;16:698–703.
291. Brown DM, Sicard GA, Flye MW, et al. Closure of complex
abdominal wall defects with bilateral rectus femoris flaps with
fascial extensions. Surgery. 1993;114:112–116.
292. Matthews MS. Abdominal wall reconstruction with an expanded
rectus femoris flap. Plast Reconstr Surg. 1999;104:183–186.
293. Caffee HH. Reconstruction of the abdominal wall by variations of
the tensor fasciae latae flap. Plast Reconstr Surg. 1983;71:348–353.
294. Mathes SJ, Hurwitz DJ. Repair of chronic radiation wounds of the
pelvis. World J Surg. 1986;10:269–280.
295. Lannon DA, Ross GL, Addison PD, et al. Versatility of the
proximally pedicled anterolateral thigh flap and its use in complex
abdominal and pelvic reconstruction. Plast Reconstr Surg.
2011;127:677–688.
296. Graham RG, Omotoso PO, Hudson DA. The effectiveness of
muscle flaps for the treatment of prosthetic graft sepsis. Plast
Reconstr Surg. 2002;109:108–113.
297. Wee JT, Joseph VT. A new technique of vaginal reconstruction
using neurovascular pudendal-thigh flaps: a preliminary report.
Plast Reconstr Surg. 1989;83:701–709.
298. Monstrey S, Blondeel P, Van Landuyt K, et al. The versatility of the
pudendal thigh fasciocutaneous flap used as an island flap. Plast
Reconstr Surg. 2001;107:719–725.
299. Hashimoto I, Murakami G, Nakanishi H, et al. First cutaneous
branch of the internal pudendal artery: an anatomical basis for the
so-called gluteal fold flap. Okajimas Folia Anat Jpn. 2001;78:23–30.
300. Yii NW, Niranjan NS. Lotus petal flaps in vulvo-vaginal
reconstruction. Br J Plast Surg. 1996;49:547–554.
301. Dev VR, Gupta A. Plastic and reconstructive surgery approaches
in the management of anal cancer. Surg Oncol Clin N Am.
2004;13:339–353.
302. Burke TW, Morris M, Roh MS, et al. Perineal reconstruction using
single gracilis myocutaneous flaps. Gynecol Oncol. 1995;57:221–225.
303. Shibata D, Hyland W, Busse P, et al. Immediate reconstruction of
the perineal wound with gracilis muscle flaps following
abdominoperineal resection and intraoperative radiation therapy
for recurrent carcinoma of the rectum. Ann Surg Oncol.
1999;6:33–37.
304. Anthony JP, Mathes SJ. The recalcitrant perineal wound after
rectal extirpation. Applications of muscle flap closure. Arch Surg.
1990;125:1371–1376.
305. Lacey CG. Vaginal reconstruction after exenteration with use of
gracilis myocutaneous flaps: the University of California, San
Francisco experience. Am J Obstet Gynecol. 1988;158:1278–1284.
306. Soper JT. Short gracilis myocutaneous flaps for vulvovaginal
reconstruction after radical pelvic surgery. Obstet Gynecol.
1989;74:823–827.
307. Schoeman BJ. The tensor fascia lata myocutaneous flap in
reconstruction of inguinal skin defects after radical
lymphadenectomy. S Afr J Surg. 1995;33:175–178.
308. Russo P, Saldana EF, Yu S, et al. Myocutaneous flaps in
genitourinary oncology. J Urol. 1994;151:1658.
309. Ramasastry SS, Liang MD, Hurwitz DJ. Surgical management of
difficult wounds of the groin. Surg Gynecol Obstet.
1989;169:418–422.
310. Santanelli F, Berlin O, Fogdestam I. The combined tensor fascia
latae/rectus femoris musculocutaneous flap: a possibility for major
soft tissue reconstruction in the groin, hip, gluteal, perineal, and
lower abdominal regions. Ann Plast Surg. 1993;31:168–174.
311. Caulfield WH, Curtsinger L, Powell G, et al. Donor leg morbidity
after pedicled rectus femoris muscle flap transfer for abdominal
wall and pelvic reconstruction. Ann Plast Surg. 1994;32:377–382.
312. Logan SE, Mathes SJ. The use of a rectus abdominis
myocutaneous flap to reconstruct a groin defect. Br J Plast Surg.
1984;37:351–353.
313. Buchel EW, Finical S, Johnson C. Pelvic reconstruction using
vertical rectus abdominis musculocutaneous flaps. Ann Plast Surg.
2004;52:22–26.
314. Tei TM, Stolzenburg T, Buntzen S, et al. Use of transpelvic rectus
abdominis musculocutaneous flap for anal cancer salvage surgery.
Br J Surg. 2003;90:575–580.
315. Henz VR. Construction of a rectal sphincter using the origin of the
gluteus maximus muscle. Plast Reconstr Surg. 1982;70:82–85.
316. Guelinckx PJ, Sinsel NK, Gruwez JA. Anal sphincter reconstruction
with the gluteus maximus muscle anatomic and physiologic
considerations concerning conventional and dynamic gluteoplasty.
Plast Reconstr Surg. 1996;98:293–302.
317. Arkoulakis NS, Angel CL, DuBeshter B, et al. Reconstruction of an
extensive vulvectomy defect using the gluteus maximus
fasciocutaneous V-Y advancement flap. Ann Plast Surg.
2002;49:50–54.
318. Goi T, Koneri K, Katayama K, et al. Modified gluteus maximus
V-Y advancement flap for reconstruction of perineal defects after
resection of intrapelvic recurrent rectal cancer: report of a case.
Surg Today. 2003;33:626–629.
319. Hurwitz DJ. Closure of large defects of the pelvic cavity by an
extended compound myocutaneous flap based on the inferior
gluteal artery. Br J Plast Surg. 1980;33:256–261.
320. Hurwitz DJ, Swartz WM, Mathes SJ. The gluteal thigh flap: a
reliable, sensate flap for the closure of buttock and perineal
wounds. Plast Reconstr Surg. 1981;68:521–532.
321. Baird WL, Hester TR, Nahai F, et al. Management of perineal
wounds following abdominoperineal resection with inferior
gluteal flaps. Arch Surg. 1990;125:1486–1489.
322. Sinna R, Qassemyar Q, Benhaim T, et al. Perforator flaps: a new
option in perineal reconstruction. J Plast Reconstr Aesthet Surg.
2010;63:e766–e774.
323. Kim JT, Ho SY, Hwang JH, Lee JH. Perineal perforator-based
island flaps: the next frontier in perineal reconstruction. Plast
Reconstr Surg. 2014;133:683e–687e.
324. Casanova D, Hulard O, Zalta R, et al. Management of wounds of
exposed or infected knee prostheses. Scand J Plast Reconstr Surg
Hand Surg. 2001;35:71–77.
325. Anract P, Missenard G, Jeanrot C, et al. Knee reconstruction with
prosthesis and muscle flap after total arthrectomy. Clin Orthop Rel
Res. 2001;384:208–216.
326. McCraw JB, Fishman JH, Sharzer LA. The versatile gastrocnemius
myocutaneous flap. Plast Reconstr Surg. 1978;62:15–23.

432.e8
CHAPTER 22 • Flap classification and applications
327. Salibian AH, Menick FJ. Bipedicle gastrocnemius
musculocutaneous flap for defects of the distal one-third
of the leg. Plast Reconstr Surg. 1982;70:17–23.
328. Linton PC. The combined medial and lateral gastrocnemius
musculocutaneous V-Y island advancement flap. Plast Reconstr
Surg. 1982;70:490–493.
329. Patel NS, Ibrahim DT, Finn HA. Knee extensor mechanism
reconstruction with medial gastrocnemius flap. Clin Orthop Rel Res.
2002;398:176.
330. Simon SR, Mann RA, Hagy JL, et al. Role of the posterior calf
muscles in normal gait. J Bone Joint Surg. 1978;60A:465–472.
331. Vaca FJ, Garramone R. Hemimuscular transfer of the soleus
muscle. Cir Plast Argent. 1983;7:12.
332. Tobin GR. Hemisoleus and reversed hemisoleus flaps. Plast
Reconstr Surg. 1985;76:87–96.
333. Beck JB, Stile F, Lineaweaver W. Reconsidering the soleus muscle
flap for coverage of wounds of the distal third of the leg. Ann Plast
Surg. 2003;50:631–635.
334. Zhang Q, Qiao Q, Yang X, et al. Clinical application of the
anterolateral thigh flap for soft tissue reconstruction. J Reconstr
Microsurg. 2010;26:87–94.
335. Gravvanis AI, Tsoutsos DA, Karakitsos D, et al. Application of the
pedicled anterolateral thigh flap to defects from the pelvis to the
knee. Microsurgery. 2006;26:432–438.
336. Kim HH, Jeong JH, Seul JH, Cho BC. New design and
identification of the medial sural perforator flap: an anatomical
study and its clinical applications. Plast Reconstr Surg. 2006;117:
1609–1618.
337. Rashid M, Hussain SS, Aslam R, et al. A comparison of two
fasciocutaneous flaps in the reconstruction of defects of the
weight-bearing heel. J Coll Physicians Surg Pak. 2003;13:216–218.
338. Hartrampf CR Jr, Scheflan M, Bostwick J 3rd. The flexor digitorum
brevis muscle island pedicle flap: a new dimension in heel
reconstruction. Plast Reconstr Surg. 1980;66:264–270.
339. Attinger CE, Ducic I, Cooper P, et al. The role of intrinsic muscle
flaps of the foot for bone coverage in foot and ankle defects in
diabetic and nondiabetic patients. Plast Reconstr Surg.
2002;110:1047–1054.
340. Sakai N, Yoshida T, Okumura H. Distal plantar area reconstruction
using a flexor digitorum brevis muscle flap with reverse-flow
lateral plantar artery. Br J Plast Surg. 2001;54:170–173.
341. Reiffel RS, McCarthy JG. Coverage of heel and sole defects: a new
subfascial arterialized flap. Plast Reconstr Surg. 1980;66:250–260.
342. Sakai S, Soeda S, Kanou T. Distally based lateral plantar artery
island flap. Ann Plast Surg. 1988;21:165–169.
343. Schwabegger AH, Shafighi M, Harpf C, et al. Distally based
abductor hallucis muscle flap: anatomic basis and clinical
application. Ann Plast Surg. 2003;51:505–508.
344. Yoshimura Y, Nakajima T, Kami T. Distally based abductor digiti
minimi muscle flap. Ann Plast Surg. 1985;14:375–377.
345. Al-Quattan MM. Harvesting the abductor digiti minimi as a
muscle plug with the lateral calcaneal artery skin flap. Ann Plast
Surg. 2001;46:651–653.
346. Grabb WC, Argenta LC. The lateral calcaneal artery skin flap (the
lateral calcaneal artery, lesser saphenous vein, and sural nerve skin
flap). Plast Reconstr Surg. 1981;68:723–730.
347. Mahan KT. Lateral calcaneal artery skin flap for posterior heel
coverage. Clin Podiatr Med Surg. 1986;3:277–287.
348. Mathes DW, Thornton JF, Rohrich RJ. Management of posterior
trunk defects. Plast Reconstr Surg. 2006;118:73e–83e.
349. Ayestaray B, Ogawa R, Ono S, Hyakusoku H. Propeller flaps:
classification and clinical applications. Ann Chir Plast Esthet.
2011;56:90–98.
350. Aho JM, Laungani AT, Herbig KS, et al. Lumbar and thoracic
perforators: vascular anatomy and clinical implications. Plast
Reconstr Surg. 2014;134:635e–645e.
351. Dusseldorp JR, Pennington DG. Quantifying blood flow in the
DIEP flap: an ultrasonographic study. Plast Reconstr Surg Global
Open. 2014;2:e228.
352. Offman SL, Geddes CR, Tang M, Morris SF. The vascular basis of
perforator flaps based on the source arteries of the lateral lumbar
region. Plast Reconstr Surg. 2005;115:1651–1659.
353. Park SW, Oh TS, Eom JS, et al. Freestyle multiple propeller flap
reconstruction (jigsaw puzzle approach) for complicated back
defects. J Reconstr Microsurg. 2015;31:261–267.
354. Fischer J, Arnold PG, Waldorf J, et al. The gluteus maximus
musculocutaneous V-Y advancement flap for large sacral defects.
Ann Plast Surg. 1983;11:517–522.
355. Ramirez OM, Orlando JC, Hurwitz DJ. The sliding gluteus
maximus myocutaneous flap: its relevance in ambulatory patients.
Plast Reconstr Surg. 1984;74:68–75.
356. Lee HB, Kim SW, Lew DH, et al. Unilateral multilayered
musculocutaneous V-Y advancement flap for the treatment of
pressure sore. Plast Reconstr Surg. 1997;100:340–345.
357. Scheflan M, Nahai F, Bostwick J 3rd. Gluteus maximus island
musculocutaneous flap for closure of sacral and ischial ulcers.
Plast Reconstr Surg. 1981;68:533–538.
358. Baran CN, Celebioglu S, Civelek B, et al. Tangentially split gluteus
maximus myocutaneous island flap based on perforator arteries
for the reconstruction of pressure sores. Plast Reconstr Surg.
1999;103:2071–2076.
359. Hurwitz DJ, Walton RL. Closure of chronic wounds of the perineal
and sacral regions using the gluteal thigh flap. Ann Plast Surg.
1982;8:375–386.
360. Foster RD, Anthony JP, Mathes SJ, et al. Flap selection as a
determinant of success in pressure s ore coverage. Arch Surg.
1997;132:868–873.
361. Verpaele AM, Blondeel PN, Van Landuyt K, et al. The superior
gluteal artery perforator flap: an additional tool in the treatment of
sacral pressure sores. Br J Plast Surg. 1999;52:385–391.
362. Foster RD, Anthony JP, Mathes SJ, et al. Ischial pressure sore
coverage: a rationale for flap selection. Br J Plast Surg.
1997;50:374–379.
363. Cochran JH Jr, Edstrom LE, Dibbell DG. Usefulness of the
innervated tensor fascia lata flap in paraplegic patients. Ann Plast
Surg. 1981;7:286–288.
364. Luscher NJ, de Roche R, Krupp S, et al. The sensory tensor
fasciae latae flap: a 9-year follow-up. Ann Plast Surg.
1991;26:306–310.
365. Scheflan M. The tensor fascia lata: variations on a theme. Plast
Reconstr Surg. 1981;68:59–68.
366. Lynch SM. The bilobed tensor fascia lata myocutaneous flap. Plast
Reconstr Surg. 1981;67:796–798.
367. Lewis VL Jr, Cunningham BL, Hugo NE. The tensor fascia lata V-Y
retroposition flap. Ann Plast Surg. 1981;6:34–37.
368. Siddiqui A, Wiedrich T, Lewis VL Jr. Tensor fascia lata V-Y
retroposition myocutaneous flap: clinical experience. Ann Plast
Surg. 1993;31:313–317.
369. Orticochea M. The musculocutaneous flap method: an immediate
and heroic substitute for the method of delay. Br J Plast Surg.
1972;25:106.
370. Akguner M, Karaca C, Atabey A, et al. Surgical treatment for
ischial sores with gracilis myocutaneous flap. J Wound Care.
1998;7:276–278.
371. Jiburum BC, Achebe JU, Akpuaka FC. Early results of operative
closure of pressure sores in traumatic paraplegics. Int Surg.
1995;80:178–180.
372. Hurteau JE, Bostwick J, Nahai F, et al. V-Y advancement of
hamstring musculocutaneous flap for coverage of ischial pressure
sores. Plast Reconstr Surg. 1981;68:539.
373. Tavakoli K, Rutkowski S, Cope C, et al. Recurrence rates of ischial
sores in para- and tetraplegics treated with hamstring flaps: an
8-year study. Br J Plast Surg. 1999;52:476–479.
374. Ao M, Mae O, Namba Y, Asagoe K. Perforator-based flap for
coverage of lumbosacral defects. Plast Reconstr Surg.
1998;101:987–991.
375. Eom JS, Hong JP. Lower back defect coverage using a free-style
gluteal perforator flap. Ann Plast Surg. 2011;67:516–519.

432.e9
References
376. Hallock GG. The buttock crease adductor magnus peninsular
perforator flap as another local flap option for repair of the ischial
pressure sore transverse adductor magnus flap. Plast Reconstr Surg.
2013;132:183e–184e.
377. Koshima I, Moriguchi T, Soeda S, et al. The gluteal perforator-
based flap for repair of sacral pressure sores. Plast Reconstr Surg.
1993;91:678–683.
378. Pan WR, Taylor GI. The angiosomes of the thigh and buttock. Plast
Reconstr Surg. 2009;123:236–249.
379. Cormack GC, Lamberty BG. The blood supply of thigh skin. Plast
Reconstr Surg. 1985;75:342–354.
380. Ahmadzadeh R, Bergeron L, Tang M, et al. The posterior thigh
perforator flap or profunda femoris artery perforator flap. Plast
Reconstr Surg. 2007;119:194–200, discussion 1–2.
381. Ramirez OM, Hurwitz DJ, Futrell JW. The expansive gluteus
maximus flap. Plast Reconstr Surg. 1984;74:757–770.
382. Paletta C, Bartell T, Shehadi S. Applications of the posterior thigh
flap. Ann Plast Surg. 1993;30:41–47.
383. Kimata Y, Uchiyama K, Ebihara S, et al. Anatomic variations and
technical problems of the anterolateral thigh flap: a report of 74
cases. Plast Reconstr Surg. 1998;102:1517–1523.
384. Luo S, Raffoul W, Luo J, et al. Anterolateral thigh flap: A review of
168 cases. Microsurgery. 1999;19:232–238.
385. Gedebou TM, Wei FC, Lin CH. Clinical experience of 1284 free
anterolateral thigh flaps. Handchir Mikrochir Plast Chir.
2002;34:239–244.
386. Chen HC, Tang YB. Anterolateral thigh flap: an ideal soft tissue
flap. Clin Plast Surg. 2003;30:383–401.
387. Lakhiani C, Lee MR, Saint-Cyr M. Vascular anatomy of the
anterolateral thigh flap: a systematic review. Plast Reconstr Surg.
2012;130:1254–1268.
388. Neligan PC, Lannon DA. Versatility of the pedicled anterolateral
thigh flap. Clin Plast Surg. 2010;37:677–681, vii.
389. Holmstrom H. The free abdominoplasty flap and its use in breast
reconstruction. An experimental study and clinical case report.
Scand J Plast Reconstr Surg. 1979;13:423–427.
390. Milloy FJ, Anson BJ, McAfee DK. The rectus abdominis muscle
and the epigastric arteries. Surg Gynecol Obstet. 1960;110:293–302.
391. Heitmann C, Felmerer G, Durmus C, et al. Anatomical features of
perforator blood vessels in the deep inferior epigastric perforator
flap. Br J Plast Surg. 2000;53:205–208.
392. El-Mrakby HH, Milner RH. The vascular anatomy of the lower
anterior abdominal wall: a microdissection study on the deep
inferior epigastric vessels and the perforator branches. Plast
Reconstr Surg. 2002;109:539–543, discussion 44–47.
393. Hamdi M, Rebecca A. The deep inferior epigastric artery
perforator flap (DIEAP) in breast reconstruction. Semin Plast Surg.
2006;20:7.
394. Angrigiani C, Grilli D, Siebert J. Latissimus dorsi
musculocutaneous flap without muscle. Plast Reconstr Surg.
1995;96:1608–1614.
395. Mun GH, Lee SJ, Jeon BJ. Perforator topography of the
thoracodorsal artery perforator flap. Plast Reconstr Surg.
2008;121:497–504.
396. Park BY, Seo SW, Mun GH. Microsurgical pedicle lengthening for
pedicled thoracodorsal artery perforator flap transfer. Ann Plast
Surg. 2014;73:174–176.
397. Gillies HD. Plastic Surgery of the Face. London: Frowde; 1920:364.
398. Bakamjian VY. A two-stage method for pharyngoesophageal
reconstruction with a primary pectoral skin flap. Plast Reconstr
Surg. 1965;36:174–184.
399. McGregor IA, Jackson IT. The groin flap. Br J Plast Surg.
1972;25:3–16.

23 
Flap pathophysiology and pharmacology
Cho Y. Pang and Peter C. Neligan
SYNOPSIS
■ Introduction
■ Pathophysiology of flap failure
■ Surgical manipulation for augmentation of pedicle flap viability
■ Pharmacological therapy for augmentation of pedicle flap viability
■ Pharmacological therapy for augmentation of free flap viability
■ Conclusion and future directions
ulceration, or congenital malformation.1–3 The clinical
problem is that flap failure as a result of ischemic necrosis
occurs in both pedicled and free flaps. In free flaps alone,
ischemic necrosis occurs in 5–10% of patients, even in expe­
rienced hands.4–10 Flap necrosis can be partial or total.11–13
Flap failure is time-consuming and costly because it requires
repeated surgery and prolonged hospitalization. In the US,
the additional operating room cost ranges from about $40 000
to $68 000 for each total free flap failure, and the additional
surgeon reimbursement ranges from $5000 to $35 000 for
each surgery.14,15 In addition, repeated surgery increases the
incidence of donor site deformity and/or morbidity, with
devastating effects on the patient. Therefore, we need to
understand the pathophysiology of ischemic necrosis in
pedicle and free flap surgery because this information may
lead us to develop effective pharmacological therapies to
prevent or salvage flap failure.
Pathophysiology of flap failure
Vasospasm and thrombosis in the
pathogenesis of pedicle and free flap failure
Clinically and experimentally, ischemic necrosis occurs
mainly in the distal portion of both pedicle and free flaps.
The general consensus is that vasospasm and thrombosis due
to surgical trauma and insufficient distal vascularity are the
main pathogenic factors in pedicle and free flap failure,3 but
little is known about the pathogenic mechanism. However,
there are published reviews on the role of vasoactive neu­
rohumoral substances in the local regulation of peripheral
vascular tone in normal and diseased states.16–21 These articles
may provide insight into the pathogenesis of vasospasm
and thrombosis in flap surgery, as illustrated in Fig. 23.1.
Briefly, endothelium-derived relaxing factors (EDRFs) such
as prostacyclin (PGI2) and nitric oxide (NO) cause relaxation
of vascular smooth muscle and inhibit platelet aggregation.
BOX 23.1  Selected abbreviations
5HT2
serotonin
Ad.VEGF165
adenoviral vectors encoding the cDNA of VEGF165
ATP
adenosine triphosphate
EDCF5
endothelium-derived contracting factors
EDRFS
endothelium-derived relaxing factors
ET-1
endothelin-1
FGF
fibroblast growth factor
MPO
myeloperoxidase
mPTP
mitochondrial permeability transitional pores
NADPH
neutrophilic nicotinamide adenine diphosphate
NE
norepinephrine
NHE-1
Na+/H+ exchange isoform-1
NO
nitric oxide
O2
•
superoxide radicals
•OH
cytotoxic hydroxyl radical
PDGF
platelet-derived growth factor
PGI2
prostacyclin
TRAM flaps
transverse rectus abdominis myocutaneous flaps
TXA2
thromboxane A2
VEGF
vascular endothelial growth factor
Introduction
Flaps, both pedicled and free, are routinely used to recon­
struct defects resulting from injury, excision of tumors,
  Access video lecture content for this chapter online at expertconsult.com

434
CHAPTER 23 • Flap pathophysiology and pharmacology
substances exacerbate vasospasm and promote thrombosis in
flap surgery.
In reperfusion of ischemic blood vessels, superoxide radi­
cals (O2
•) are produced by platelets, neutrophils, and endothe­
lial cells and these free radicals can damage vascular walls
during reperfusion (see Fig. 23.1).
Xanthine dehydrogenase/xanthine oxidase
enzyme system in pathogenesis of ischemia–
reperfusion injury in free flap surgery
In free flap surgery, skin and muscle are subjected to warm
(room-temperature) global ischemia under vascular clamp
control during transfer from donor site to recipient site prior
to re-anastomosis. Human muscle and skin can withstand
2–2.5 hours and 6–8 hours of warm global ischemia,
respectively.22–26 Excessive ischemic insult can result in
ischemia–reperfusion injury caused by energy depletion
and formation of oxygen-derived free radicals, as shown in
Fig. 23.2. During prolonged ischemia, adenosine triphos­
phate (ATP) in skin and muscle is catabolized stepwise
to hypoxanthine, with concomitant increase in cytosolic
Ca2+.27 At the same time, a cytosolic protease is activated by
intracellular Ca2+ and it converts xanthine dehydrogenase
to xanthine oxidase.28,29 During reperfusion, the xanthine
oxidase generates superoxide (O2
•) by univalent reduction of
On the other hand, endothelium-derived contracting factors
(EDCFs) such as thromboxane A2 (TXA2), and endothelin-1
(ET-1) raise vascular tone. Under physiological conditions,
a balance of vascular effects between EDCFs and EDRFs
maintains adequate tissue perfusion. However, an imbalance
can occur as a result of surgical trauma, as shown in Fig. 23.1.
Specifically, traumatized sympathetic nerve endings release
norepinephrine (NE), causing vasoconstriction and platelet
aggregation. The NE released by the sympathetic nerve
endings, leukotriene B4, serotonin (5HT2) and TXA2 released
by the platelets, and the ET-1 released by the traumatized
vascular endothelial cells can cause vasoconstriction and
intravascular platelet aggregation, especially in the small
arteries in the distal portion of the flap where the perfusion
pressure is low and the concentration of these vasoconstrictive
substances is high due to the downstream effect. Hemoglobin
from hemolyzed red blood cells (e.g., hematoma) is also a
potent vasoconstrictor. The histamine released by the mast
cells changes the membrane permeability, resulting in edema
formation. Furthermore, the synthesis and release of EDRFs
such as PGI2 and NO from the traumatized vascular endo­
thelium are depressed. In addition, the rate of endothelial
degradation of NE and 5HT2 by catechol-O-methyl transferase
and monoamine oxidase, respectively, is reduced in situations
of impaired endothelial function. The end result is that there
are high local levels of vasoconstrictive and prothrombotic
neurohumoral substances in surgical trauma and these
Fig. 23.1  Vasoconstriction in surgical trauma and vascular damage in
ischemia–reperfusion injury. In surgical trauma, norepinephrine is
released by sympathetic nerve endings and thromboxane A2, leukotriene
B4, and serotonin are released by traumatized platelets and hemoglobin
by red blood cells to cause vasoconstriction. Traumatized endothelial
cells also decrease synthesis of vasodilating prostacyclin and
endothelium-derived relaxing factor/nitric oxide (EDRF/NO). In
reperfusion of ischemic blood vessels, superoxide radicals (O2
•) are
produced by platelets and neutrophils. These free radicals can damage
blood vessels.
Endothelium
Vascular smooth
muscle cell
Mast cell
Red
blood
cell
Sympathetic
nerve
Release
inhibition
Release
Ischemia /
Reperfusion
Surgical
trauma
Histamine
Neutrophils
Hemoglobin
(Hematoma)
Prostacyclin
EDRF(NO)
Platelets
Endothelin
Norepinephrine
Thromboxane A2
Leukotriene B2
Serotonin
O2
O2
O2
O2
O2
O2

435
Pathophysiology of flap failure
Neutrophilic nicotinamide adenine
diphosphate (NADPH) and myeloperoxidase
(MPO) enzyme system in pathogenesis of
ischemia/reperfusion injury in free flap
surgery
There is accumulated evidence to indicate that neutrophils
may play an important role in ischemia–reperfusion injury in
free flap surgery. For example, it is well known that activated
neutrophils produce large amounts of O2
• via NADPH
oxidase, and these O2
• dismutates yield a high concentration
of H2O2 and •OH, causing tissue damage.38 MPO, which is
unique and abundant in neutrophils, catalyzes the conversion
of H2O2 to hypochlorous acid (HOCl), a potent cytotoxic
oxidizing agent (H2O2 + Cl− + H+ → HOCl + H2O).39,40 Further­
more, it was reported that treatment with monoclonal anti­
bodies against neutrophil–endothelium adhesion molecules
attenuated ischemia–reperfusion-induced skin necrosis in
rabbit ears,41 rat epigastric island skin flaps,42 and skin and
muscle in pig latissimus dorsi musculocutaneous flaps.43
Treatment with monoclonal antibody against neutrophil–
endothelium adhesion molecules also attenuated arteriolar
vasoconstriction induced by ischemia–reperfusion injury.44
Finally, neutrophil depletion (~95%) with mechlorethamine
significantly reduced necrosis in pig latissimus dorsi muscle
flaps subjected to 5 hours of warm ischemia and 48 hours of
reperfusion.37 Also, neutrophil depletion attenuated vascular
injury in dog gracilis muscle subjected to 4 hours of warm
ischemia and 1 hour of reperfusion.45
Paradoxically, there are arguments against the important
role of neutrophils in the pathogenesis of animal or human
myocardial ischemia–reperfusion injury.46–48 Several investiga­
tors found that ischemia–reperfusion injury could be induced
in neutrophil-free systems such as in cultured animal cardio­
myocytes49 and human atrial strips50,51 and in isolated perfused
animal hearts.52–54 In clinical studies, free oxyradical scaven­
gers were not effective in protecting myocardium from
ischemia–reperfusion injury.55,56 Furthermore, although mono­
clonal antibody to intercellular adhesion molecule-1 and
anti-CD18 antibodies were effective in protecting myocardium
against ischemia–reperfusion in laboratory animals,57,58 clini­
cal trials with these agents yielded negative results.59–61 More
recently, we observed that ischemia–reperfusion injury was
also induced in human rectus abdominis muscle strips cul­
tured in neutrophil-free buffer.62 There is the possibility of
species difference in the role of neutrophils in the pathogenesis
of ischemia–reperfusion injury. Therefore, it is important to
clarify the causal role of neutrophils in ischemia–reperfusion
injury in human skin and skeletal muscle.
Intracellular Ca2+ overload in pathogenesis
of ischemia–reperfusion injury in
free flap failure
Recently, experimental evidence has shown that intracellular
Ca2+ overload plays a key role in causing cell death during
myocardial reperfusion.63 The pathogenic mechanism is sum­
marized in Fig. 23.3. It appears that, in sustained ischemia,
mitochondrial ATP synthesis ceases and glycolysis ensues,
resulting in a net breakdown of ATP and an accumulation of
Fig. 23.2  Pathogenesis of oxygen-derived free radicals in reperfusion of ischemic
tissues. AMP, adenosine monophosphate; ATP, adenosine triphosphate; O2
•,
superoxide; H2O2, hydrogen peroxide; •OH, hydroxyl radical; 1O2, singlet oxygen;
RO2
•, peroxy radicals; ROOH, hydroperoxide.
ATP
AMP
Adenosine
Inosine
Xanthine
oxidase
Xanthine
dehydrogenase
Xanthine
+
Superoxide
Hypoxanthine
Tissue damage
O2
From reperfusion
O2
1O2
ROOH
H2O2
OH
RO2
Protease
Tissue ischemia
(ATP catabolism)
Biological damage
(by superoxides
and derivatives)
molecular oxygen in the presence of hypoxanthine.30 The
unstable O2
• forms H2O2 spontaneously by dismutation.
Furthermore, the unstable O2
• also interacts with H2O2 in the
presence of a transition metal (e.g., iron) to form the most
potent cytotoxic hydroxyl radical (•OH) through the Haber–
Weiss (Fenton) reaction,31 as shown in Fig. 23.2. There is
evidence to suggest that this hypoxanthine/xanthine oxidase
system is a main source of oxyradicals in ischemic rat skin
and muscle.32,33 Furthermore, inhibition of xanthine oxidase
activity by allopurinol and depletion of xanthine oxidase
with a tungsten diet have been shown to attenuate the
microvascular damage in rat skeletal muscle subjected to 2
hours of ischemia and 30 minutes of reperfusion.34
However, there is also evidence to indicate that the
hypoxanthine/xanthine oxidase system is not a main source
of oxyradicals in pig and human skin and skeletal muscle.
Control pig and human skin samples have been found to
contain minimal xanthine oxidase activity, almost 40 times
less than that of the rat, and xanthine oxidase activity did not
rise during the first 8 hours of ischemia in these experiments.35
In pigs, intravenous allopurinol given 60 minutes before
ischemia did not protect cutaneous or musculocutaneous
flaps from necrosis when subsequently subjected to 8 hours
of warm ischemia and 5 days of reperfusion.36 Similarly, we
observed that xanthine oxidase activity in pig and human
skeletal muscle was minute (<0.5 mU/g wet weight) com­
pared with that of the rat.37 In addition, we observed that 5
days of competitive xanthine oxidase inhibitor treatment
(allopurinol 25 mg/kg i.v., b.i.d.) starting 2 days before ische­
mia or 3 days of noncompetitive xanthine oxidase inhibitor
treatment (oxypurinol, 25 mg/kg, i.v., b.i.d.) starting 15
minutes before reperfusion did not attenuate pig latissimus
dorsi muscle necrosis when subjected to 5 hours of ischemia
and 48 hours of reperfusion.37

436
CHAPTER 23 • Flap pathophysiology and pharmacology
death.52,71 Recently, we have seen evidence to suggest that
mitochondrial Ca2+ overload plays an important role in
ischemia–reperfusion in skeletal muscle and this will be dis­
cussed later, along with the therapeutic treatment aimed at
preventing mitochondrial Ca2+ overload.
Pathogenesis of no-reflow phenomenon in
free flap surgery
May et al. used rabbit island epigastric skin free flaps to study
the pathogenesis of the no-reflow phenomenon in free flap
surgery.75 They observed that ischemia induced swelling of
the endothelial and parenchymal cell, narrowing of the capil­
lary lumen, which led to intravascular aggregation of blood
cells, and leakage of intravascular fluid into the interstitial
space to form edema. This pathology increased with the
increase in length of ischemic time from 1 to 8 hours and the
obstruction of blood flow reached a point of irreversibility
after 12 hours of ischemia, leading to no reflow and ultimate
death of the flap. Three pathogenic mechanisms have been
suggested to play a central role in the development of the
no-reflow phenomenon in the skeletal muscle of laboratory
animals: (1) oxygen-derived free radicals causing damage in
the endothelial and parenchymal cells; (2) this cell membrane
damage allowing Ca2+ influx, resulting in intracellular over­
load; and (3) change in arachidonic acid metabolism resulting
in synthesis of less vasodilating and antithrombotic PGI2 by
the endothelium and increased synthesis of vasoconstricting
and thrombotic TXA2 by platelets.76
Surgical manipulation for augmentation
of pedicle flap viability
Clinically and experimentally, there are several surgical
manipulations which have proved effective in augmenting
flap viability.
Flap design in augmentation of
pedicle flap viability
One of the misleading principles in plastic surgery is that the
viable length of a skin flap depends on the width of the
pedicle. Milton was the first to disprove this principle.1,77–79
Using a random-pattern skin flap model in the pig, it was
demonstrated that the ultimate surviving length of a pedicle
flap is determined by the balance between perfusion pressure
and vascular resistance. Increasing the width of pedicle flaps
merely adds additional vessels of the same type and the same
perfusion pressure and thus cannot increase the length of flap
viability (Fig. 23.4). However, in other locations of the body,
increasing the width of the pedicle may increase the chance
of including a large artery. Therefore, one of the surgical
manipulations to augment flap viability is the conversion of
a random-pattern skin flap to an arterialized or axial skin flap
by incorporating a direct artery or a larger perforator.
Surgical delay in augmentation of
pedicle flap viability
Surgical delay and vascular delay are proven techniques for
augmenting flap viability in human patients,80–84 as well as in
lactate and intracellular H+,64 causing intracellular acidosis.
This build-up of intracellular H+ activates the Na+/H+
exchange isoform-1 (NHE-1) antiporter, resulting in extrusion
of H+ and accumulation of intracellular Na+ to restore intracel­
lular pH. There is a further increase in intracellular Na+
accumulation because Na+ extrusion is limited by inactivation
of the energy-dependent Na+-K+-ATPase pump.65,66 Elevation
of intracellular Na+ concentration causes an increase in intra­
cellular Ca2+ by activation of the Na+/Ca2+ exchanger causing
Ca2+ influx.65,67–70 If these events continue, the cytosolic Ca2+
will be overloaded, and significant uptake of Ca2+ from the
cytosol to the mitochondria will occur, resulting in mitochon­
drial Ca2+ overload71 which causes depolarization of mito­
chondria and impairs ATP synthesis, resulting in cell necrosis52
(see Fig. 23.3). However, the NHE-1 may be inhibited72 if the
extracellular acidosis is more pronounced than the intracel­
lular acidosis after a prolonged period of ischemia.73 At
reperfusion, the rapid washout of the extracellular H+ reacti­
vates the NHE-1, resulting in further extrusion of intracellular
H+, and further accumulation of intracellular Na+, causing
further cytosolic Ca2+ overload through Na+/Ca2+ exchange.67,74
Again, cytosolic Ca2+ overload causes mitochondrial Ca2+
overload, impairing ATP synthesis and resulting in cell
Fig. 23.3  Proposed role of intracellular Ca2+ overload in the pathogenesis of
ischemia–reperfusion injury. ATP, adenosine triphosphate.
Ischemia
Intracellular acidosis
Elevation of intracellular Na+ concentration
Activation of Na+/Ca+ exchanger
Extrusion of Na+ and influx of Ca2+
Necrosis (cell death)
Intracellular Ca2+ overload
Activation of Na+/H+ exchanger isoform-1 (NHE-1)
Opening of mitochondrial permeability pores
Depolarization of mitochondria and impairing ATP synthesis
Extrusion of H+ and influx of Na+ to restore intracellular pH

437
Surgical manipulation for augmentation of pedicle flap viability
free flaps are a good example as the free TRAM is perfused
by the more dominant deep inferior epigastric pedicle rather
than the less dominant superior epigastric vessels that supply
the pedicled TRAM.105–110 However, in some situations free
flap surgery is not available. It requires specialized microsur­
gical staff and equipment and long operating room time.
Furthermore, free flap surgery is not without morbidity and
flap ischemic necrosis due to thrombosis and vasospasm
occurs in 5–10% of patients.4–10,110 Therefore, there is the need
to understand the mechanism of the surgical delay phenom­
enon through research to identify pharmacological strategies
to prevent/treat ischemic necrosis.
Mechanism of surgical delay in augmentation
of pedicle flap viability
Many investigators have studied the surgical delay phenom­
enon in laboratory animals in order to gain insight into the
pathogenesis and pharmacological treatment for skin flap
ischemic necrosis. Several hypotheses have emerged from
these studies.
Surgical delay procedure reduces
arteriovenous (AV) shunt flow
Reinisch reported good correlation between postoperative
fluorescein staining and the eventual skin viability in pig skin
flaps. He detected warm skin temperature beyond the fluo­
rescein dye marker in the distal portion of the pig skin flap.111
He also demonstrated 51Cr-labeled red blood cells and tech­
netium and 85Sr-microsphere (15 µm) activity beyond the fluo­
rescein dye staining in acute pig skin flaps.111 Taken together,
he hypothesized that, in acute skin flap surgery, distal ische­
mic necrosis was caused by opening of AV shunt flow as a
result of sympathetic denervation. He speculated that shunt
flow occurred throughout the skin flap and the flow in the
proximal areas is sufficient to supply both the AV and capil­
lary (nutrient) blood flow, but the shunting became lethal in
the distal areas of the skin flap where the total blood flow was
low. In surgical delay, the bipedicle skin flap provided suffi­
cient blood supply during the early period of sympathetic
denervation and opening of AV shunts. Pearl presented data
from rat abdominal arterial skin flaps, which supported
Reinisch’s hypothesis, and also suggested that surgical delay
allowed the skin flap to recover from its hyperadrenergic state
before converting the bipedicle to single-pedicle skin flaps.112
However, these observations were not supported by other
investigators. For example, Prather et al., using various labo­
ratory techniques (fluorescein dye test, xenon clearance,
angiography, 51Cr-tagged red blood cells and thermometry),
failed to detect any evidence of vascular perfusion in the
non-fluorescein distal portion of acute axial pattern skin flaps
in the pig.113 In contrast to Palmer’s findings114 in rat dorsal
skin flaps, Cutting et al.115,116 did not observe persistent adren­
ergic denervation in delayed bipedicle skin flaps. Later, Guba
used 15 µm and 50 µm radioactive microspheres to measure
capillary (nutrient) and total blood flow, respectively, and to
calculate AV shunt flow in bipedicle axial pattern pig skin
flaps. Both capillary and AV shunt flow increased between 2
and 7 days of delay in pig bipedicle skin flaps, but this increase
in capillary blood flow in delayed bipedicle skin flaps was not
the result of a decrease in AV shunt flow.100
laboratory animals such as mice, rats, rabbits, and pigs.85–98 It
takes two to three stages in surgical delay of pedicle skin flaps
in order to augment flap viability. Specifically, a skin flap is
mapped out on the donor site and incised on its two longitu­
dinal sides. The flap is then undermined to form a bipedicle
flap and is sutured back to the donor site. Two to three weeks
after construction of the bipedicle flap, the third side (distal
end) is cut in one or two stages at 2–3 days apart. At the end
of this stage, a single pedicle flap is completely raised and the
distal portion of the flap is moved to the recipient site for
wound coverage without skin necrosis.1,99 In studies with pig
random-pattern skin flaps, we and other investigators showed
that surgical delay increased skin flap capillary blood flow
between 2 and 7 days of delay.100,101 This increase in capillary
blood flow was mainly in the distal random portion of the
delayed skin flaps.101
Vascular delay in augmentation of pedicle
flap viability
In mice, rats, and rabbits, vascular delay for augmenting
blood flow and viability in the distal portion of latissimus
dorsi muscle flaps was achieved by dividing distal perforat­
ing arteries at 1–2 weeks prior to raising the muscle flaps.93,95,96
This phenomenon was also achieved in transverse rectus
abdominis myocutaneous (TRAM) flaps in laboratory animals
as well as in human patients. Division of perforators or one
or two dominant arteries that supply blood to the rectus
abdominis muscle 2–3 weeks before flap surgery significantly
augmented viability in TRAM flaps in rats91,92,94,97 and aug­
mented skin and muscle blood flow and viability in TRAM
flaps in pigs.91,92 In human patients, ligation of the deep infe­
rior epigastric arteries 2–4 weeks before flap surgery aug­
mented skin blood supply83,102,103 and viability in TRAM
flaps.80–82,84
Surgical and vascular delay have been proven clinically
effective in augmenting flap viability, but these surgical pro­
cedures are costly and time-consuming. They require at least
one additional surgical step done under general anesthesia.
Vascular delay by embolization does not require general
anesthesia, but it requires local anesthesia and catheterization
performed in the interventional radiology department.104
Recently, “recharging” of the TRAM flap has been described
as an alternative technique to augment flap perfusion.105 The
evolution of microsurgery saw the development of free flaps.
The idea was to improve flap blood flow and viability. TRAM
Fig. 23.4  The length-to-width ratio concept in flap design.
10 cm
4 cm
1 cm

438
CHAPTER 23 • Flap pathophysiology and pharmacology
was also seen in vascular delay of pig TRAM flaps within
3–4 days of delay and it is unlikely that an increase in arterial
density (arteriogenesis) could have occurred during this short
period of time. Therefore, these investigators described this
phenomenon as vascular territory expansion by recruitment
(opening) of existing arteries, as illustrated in Fig. 23.5.90
Opening of existing blood vessels was demonstrated by
Taylor and colleagues in vascular delay of skin flaps in the
guinea pig, rabbit, dog, pig, and human,144–147 and by Yang
and Morris in vascular delay of rat skin flaps,148,149 and this
phenomenon was labeled by these investigators as angio­
some territory expansion by opening of existing choke blood
vessels.
Surgical delay procedure induces angiogenesis
Lineaweaver et al. reported that vascular delay increased the
viability of the skin paddle of rat TRAM flaps and this protec­
tive effect of vascular delay was associated with a significant
increase in gene expression of vascular endothelial growth
factor (VEGF) and basic fibroblast growth factor (FGF) in
the skin paddle of the rat TRAM flaps within 12 hours of
vascular delay. These investigators speculated that these
cytokines induced vasodilation and angiogenesis to augment
skin paddle viability in rat TRAM flaps.150 The vascular
Subsequently, using 15 µm and 50 µm radioactive micro­
spheres as well as fluorescein dye, Kerrigan117 found no evi­
dence of AV shunt flow in the distal portion of acute random
and arterial pig skin flaps destined to necrose, as indicated by
lack of fluorescein penetration. Finally, using a similar radio­
active microsphere technique, Pang et al. demonstrated that
AV shunts played no important role in the pathogenesis of
distal ischemic necrosis in random-pattern skin flaps in the
pig and augmenting distal skin viability by surgical delay did
not rely on closing of AV shunts, but vasodilation of existing
blood vessels.101,118 It is important to point out that there may
also be species differences in the extent of AV shunt flow in
the skin assessed by the radioactive microsphere technique.
Specifically, our lab observed in the pig that the AV shunt flow
in the control skin and in the skin of acute and delayed
random-pattern skin flaps within 6 hours postoperatively was
~60% of the total blood flow.101 However, Sasaki and Pang119
observed in the rat that the AV shunt flow in abdominal island
skin flaps within 6 hours postoperatively was ~10% of the
total skin blood flow. More recently, Kreidstein et al.120 in our
laboratory observed that the AV shunt flow in isolated per­
fused human para-umbilical skin was ~1%. Taken together,
these studies seem to indicate that AV shunt flow does not
play an important role in the pathogenesis of distal ischemic
necrosis in acute pedicle skin flaps.
Surgical delay procedure depletes
vasoconstriction and prothrombotic
substances in the skin flap
Local tissue content of vasoconstricting and prothrombotic
substances such as NE, TXA2, 5HT and ET-1 are known to
be elevated by surgical trauma.3,121–135 These substances are
released locally by traumatized blood cells, endothelial cells,
and sympathetic nerve endings (see Fig. 23.1). These are
potent vasoconstrictors in skin vasculature.134,136–143 There is a
general consensus that vasospasm and thrombosis play an
important role in the pathogenesis of ischemic necrosis in
acute skin flaps and the surgical delay procedure reduces local
production and also allows time to deplete the vasoconstrict­
ing and prothrombic substances before converting the
bipedicle flap to single-pedicle flaps. In the past, research in
skin flap surgery was focused on the use of vasodilating and
antithrombotic drugs to augment skin flap viability. So far, the
outcomes of pharmacological therapy for the prevention or
treatment of pedicle flap ischemic necrosis are disappointing
and will be discussed later.
Surgical delay procedure induces vascular
territory expansion by opening existing
choke arteries
Pang et al. studied the capillary blood flow in delayed random-
pattern pig skin flaps. We found that the capillary blood flow
increased significantly within 2 days of delay and a maximum
increase in skin flap capillary blood flow occurred between
2 and 3 days of delay, and remained unchanged between
4 and 14 days of delay without an increase in density of
arteries (arteriogenesis) assessed by histology. This increase
in capillary blood flow occurred mainly in the distal portion
of the skin flap.101 Similar increase in capillary blood flow
Fig. 23.5  Opening of existing blood vessels (choke vessels) in the distal portion
of the surgically delayed skin flap.
Choke vessels
Distal end
Artery
Pedicle

439
Pharmacological therapy for augmentation of pedicle flap viability
Angiogenic cytokine protein or gene therapy
for augmentation of pedicle flap viability
Angiogenic cytokines such as VEGF, FGF, and platelet-derived
growth factors (PDGF) are known to induce an increase in
capillary density (angiogenesis). Recently, flap research has
been focused on the use of local angiogenic cytokine protein
therapy to augment flap viability. For example, improved
viability was observed following local subdermal injection of
VEGF165 immediately after elevation of rat dorsal random-
pattern skin flaps;178,179 local interarterial injection of VEGF165
immediately after raising of rat epigastric island skin flaps;180,181
and injection of VEGF165 into the rectus abdominis muscle 20
days before construction of TRAM flaps in the rat.182 There is
also evidence to indicate that FGF can augment skin flap
viability. This has been observed following intradermal injec­
tion of FGF 30 minutes before surgery in rat dorsal random-
pattern skin flaps;183 subdermal injection of FGF immediately
after surgery and at 48 hours postoperatively in rat dorsal
random-pattern skin flaps;184 and subdermal injection of FGF
18 days before construction of arterial skin flaps in mouse
ears.185 Last but not least, it was reported that local PDGF
treatment mimicked the surgical delay phenomenon in aug­
menting latissimus dorsi muscle viability in the mouse.186 So
far none of these angiogenic cytokines has been tested on
tight-skinned animals such as the pig. Since the angiogenic
cytokines were effective in augmenting skin flap viability
when given several days before or immediately after surgery,
it is possible that vasodilation may play an important role in
this mechanism. Khan et al. in our laboratory used the rat
dorsal random-pattern skin flap model to study the mecha­
nism of acute local intradermal VEGF165.187 These studies
showed that subdermal injection of VEGF165 at the time of
surgery effectively attenuated pedicle skin flap ischemic
necrosis in a dose-dependent manner, mainly by inducing the
synthesis/release of the vaso-relaxing factor NO. The mecha­
nism by which VEGF165 augmented skin flap viability
appeared to depend on the vasodilator effect of VEGF165 in the
early stage (within 6 hours) after surgery, followed by the
angiogenic effect (i.e., increase in capillary density) of VEGF165
in the later stage after surgery. It is important to point out that
VEGF165 is a potent vasodilator in skin vasculature. Specifi­
cally, we observed that VEGF165 was seven times more potent
than acetylcholine in inducing skin vasodilation in isolated
perfused pig island buttock skin flaps.188
The biological half-life of VEGF165 is 30–45 minutes in
normoxic and 6–8 hours in hypoxic conditions.189 It is possible
that the effectiveness of VEGF165 protein therapy is limited by
its short half-life and VEGF165 gene therapy may be the key to
providing a steady release of VEGF165 perioperatively.190 Spe­
cifically, local intradermal or subcutaneous injection of lipo­
somal or adenoviral vectors encoding the cDNA of VEGF165
(Ad.VEGF165) given at 0.5, 2, 3, 7, or 14 days before surgery
was shown to augment skin flap viability in the rat.191–194 Local
subcutaneous injection of VEGF165 plasmid DNA 7 days pre­
operatively also increased skin viability in rat musculocutane­
ous (TRAM) flaps.195 Of interest is the observation that
the number of capillaries and arterioles were significantly
increased in the skin of rat musculocutaneous (TRAM) flaps
when Ad.VEGF165 was injected subcutaneously 14 days before
surgery.196 However, it is important to point out that review
of the data in the literature to date indicates that the efficacy
mechanism of surgical delay is still unclear. However, it was
previously reported that the angiogenesis inhibitor endostatin
inhibited ischemia-induced microvascular density and viabil­
ity of mouse dorsal random-pattern skin flaps.151 Therefore,
endostatin can be used in the future to investigate the role of
angiogenesis and arteriogenesis in surgical delay in skin flap
surgery in laboratory animals.
Pharmacological therapy for
augmentation of pedicle flap viability
As discussed previously, the surgical delay procedure is costly
and time-consuming. Therefore, much research has been
focused on drug therapy for augmenting blood flow and
viability in pedicle flap surgery.
Drug therapy against vasoconstriction and
thrombosis in pedicle flap surgery
Vasoconstricting and prothrombotic substances such as NE,
TXA2, 5HT, and ET-1 are known to be elevated in skin flap
surgery as a result of surgical trauma.121–131,135 These are very
potent vasoconstrictors.134,136–142 In the past, research in skin
flap surgery was focused on the use of vasodilating and
antithrombotic drugs to augment skin flap viability. These
studies were reviewed in detail up to 1990 by various
investigators and will not be discussed here.3,117,152,153 The
categories of drugs included: α-adrenoreceptor antagonists;
drugs causing depletion of catecholamine in nerve terminals;
drugs preventing catecholamine release from the nerve termi­
nal; β-adrenoreceptor agonists; direct vasodilators, calcium
channel blockers, hemorrheological drugs; vasodilating eico­
sanoids and their synthesis inhibitors; anti-inflammatory
drugs; drugs inhibiting adherence and accumulation of neu­
trophils; and free radical scavengers. More recently, research
in drug therapy for augmenting flap viability also focused on
vasodilation,154–170 antithrombosis,171 and inhibition of neutro­
phil from adherence and accumulation.172 In general, the
results with these vasodilating and antithrombotic drug treat­
ments in augmenting pedicle flap viability were controversial,
inconclusive, or very modest at best, compared with surgical
delay. Finally, most of these studies were performed in loose-
skinned laboratory animals (e.g., rats, rabbits) whose skin
vasculature and anatomy are likely different from those of the
human.78 Using more clinically relevant pig pedicle skin flap
models, Pang and colleagues tested several drugs, which were
reported to augment rat skin flap viability by other investiga­
tors. We found that neither skin blood flow nor viability
was significantly improved by the following categories
of drug: glucocorticoid,173 α-adrenoreceptor antagonists,88
vascular smooth-muscle relaxants,174,175 β-adrenoreceptor
agonist,174 TXA2 synthesis inhibitor,174 TXA2 receptor antago­
nist,174 and vasodilating prostanoids.176 We also found that
5HT2 receptor antagonists augmented skin flap viability in the
pig, but the beneficial effect was modest compared with surgi­
cal delay.174,177 In conclusion, the mechanism of surgical or
vascular delay is unclear. So far, there is no effective drug
therapy which can mimic surgical or vascular delay in aug­
menting skin flap viability.

440
CHAPTER 23 • Flap pathophysiology and pharmacology
clinical free flaps.211 Furthermore, there is clinical evidence to
indicate that a low dose of aspirin is effective in preventing
coronary graft occlusion given preoperatively or within 24
hours of surgery.212,213
The low-molecular-weight dextran 40 (MW 40 000) and
dextran 70 (MW 70 000) are known to have blood volume
expansion and antithrombogenic effects in humans.213
Dextran 40 is the most popular dextran used to decrease
platelet aggregation and to improve blood flow in free flap
surgery. The effective doses have been reviewed elsewhere.200
However, dextran 40 also has undesirable side effects such
as anaphylaxis, pulmonary and cerebral edema, and renal
failure.214 In addition, there is clinical evidence to indicate
that pre- or postoperative low-molecular-weight dextran
treatment may not be effective in augmenting free flap
viability.215–217
Thrombolytic agents
While early detection and re-exploration are crucial for sal­
vaging failing free flaps, those flaps unresponsive to standard
interventions may benefit from the selective use of thrombo­
lytics for lysing formed thrombi.218 The common thrombolytic
agents that have been used successfully in clinical free flaps
are streptokinase,219–227 and recombinant tissue plasminogen
activator (tPa).228–231 The effective doses of these thrombolytic
agents have also been discussed.199,200 Results from these
studies are encouraging and these agents are now commonly
used, particularly in take-back situations. However, most, if
not all, of these studies were small or in the form of case
reports.
Antispasmodic agents
Papaverine, nifedipine, and lidocaine are the most common
topical antispasmodic drugs used in clinical microsurgery.
Papaverine is an opiate alkaloid, which relaxes vascular
smooth muscle, especially during spasms. It inhibits phos­
phodiesterase, the enzyme involving the breakdown of cyclic
adenosine monophosphate (cAMP), resulting in accumula­
tion of cAMP, causing vasodilation.232 Nifedipine is a calcium
channel blocker. The mechanism of action is inhibition of
calcium influx into the arterial smooth-muscle cells, thus
causing smooth-muscle cell relaxation.233 The vasodilator
effect of lidocaine is the result of its effect on the Na+/Ca2+ ion
exchanger pump causing a reduction in intracellular calcium
content, resulting in vasodilation.234
Preischemic and postischemic
pharmacological conditioning against
ischemia–reperfusion injury in
free flap surgery
In the past 20 years, research in ischemia–reperfusion injury
in cardiac and skeletal muscle has been focused on the efficacy
and mechanism of preischemic and postischemic condition­
ing against ischemia–reperfusion injury.235 This information is
important because it may provide insight into the identifica­
tion of new drugs for the prevention or salvage of skin and
skeletal muscle from ischemia–reperfusion injury in free flap
and replantation surgery.
of rat dorsal skin flap viability augmentation was similar
between VEGF165 protein and gene therapy, and the skin flap
viability was about 15–20% lower than that of surgical
delay.187,197 Therefore, more than VEGF165 is required to mimic
surgical delay in augmenting flap viability.
Pharmacological therapy for
augmentation of free flap viability
Vasospasm, thrombosis, and ischemia–reperfusion injury are
the main causes of free flap failure. At the present time, there
are relatively safe drugs which are used clinically to prevent
or treat vasospasm and thrombosis in flap surgery. However,
drug therapy for ischemia–reperfusion injury remains a
subject of animal research.
Drug therapy for prevention of vasospasm
and thrombosis in free flap surgery
Drug therapy is used by some surgeons to prevent or treat
anastomotic vasospasm and thrombosis in free flap surgery.
These drugs can be classified into three categories and
their dosage, efficacy, and treatment guidelines have been
reviewed.198–200
Anticoagulant agents
Heparin, aspirin, and dextran are the three common antico­
agulants used in microsurgery, but their efficacy is unclear.
For example, it has been reported that intravenous heparin
treatment reduced the incidence of anastomotic thrombosis
when given before the restoration of blood flow in the
rabbit.201 Subsequently, results from two clinical studies in
free flap surgery indicated that low dosage of intraoperative
heparin treatment (3000 or 5000 units intravenously) did not
increase the rate of hematoma formation or intraoperative
bleeding. However, these low doses of heparin treatment
also did not have any significant effect on the prevention of
microvascular thrombosis.202,203 Obviously, a higher systemic
dose of heparin is required. Some surgeons recommend an
intraoperative bolus injection of 100–150 units/kg of intrave­
nous heparin before cross-clamping and a supplement injec­
tion of 50 units/kg of heparin every 45–50 minutes until
re-establishment of blood flow after anastomosis.204 However,
this is not common practice. More clinical research is
required to identify an effective dose of heparin for the pre­
vention of anastomotic thrombosis without hematoma for­
mation in free flap surgery.
It was observed in the rabbit that a low dose of aspirin
(10 mg/kg) caused an antithrombotic effect because it reduced
TXA2 (vasoconstrictor) formation in the platelet to a greater
extent than PGI2 (vasodilator) formation in the endothelium.205
Low doses of aspirin were also observed to inhibit anasto­
motic thrombosis and improve the microcirculation in the
rat.206 In humans, lower doses of aspirin (40–325 mg) were
observed to inhibit platelet cyclo-oxygenation production of
TXA2 with minimal inhibition of endothelium-derived pro­
duction of PGI2.207–209 However, more than 24 hours are
required to achieve maximal cyclo-oxygenation inhibition.207,210
It was also reported that a low oral dose of aspirin (325 mg/
day) did not cause postoperative hematoma formation in

441
Pharmacological therapy for augmentation of free flap viability
Subsequently, Moses, another of our research fellows,
demonstrated that the infarct-protective effect of remote
preischemic conditioning in pig skeletal muscle was bipha­
sic258 and the time course was similar to that seen in local
preischemic conditioning in the myocardium of rabbits259–261
and dogs262 and in the skeletal muscle of rats.263,264 Specifi­
cally, an early phase of infarct protection started immediately
after hind limb remote preischemic conditioning, waned
within 4 hours, and completely disappeared in less than
6 hours after remote preischemic conditioning (Fig. 23.7).
The late phase (second window) of infarct protection (re)
appeared within 24 hours after hind limb remote preisch­
emic conditioning and lasted up to 72 hours. More impor­
tantly, it was observed that sarcolemmal and mitochondrial
KATP channels play a central role in the trigger and mediator
mechanism, respectively.258 The logical approach in the
future is to identify a nonhypotensive prophylactic drug
(e.g., sarcolemmal KATP channel opener) to be taken orally 24
Local preischemic conditioning against ischemia–
reperfusion injury in skeletal muscle
The phenomenon of preischemic conditioning against
ischemia–reperfusion injury was first recognized in dog
myocardium.236 Subsequently, Mounsey et al. in our labora­
tory demonstrated this phenomenon for the first time in pig
muscle flaps.237,238 Specifically, we reported that instigation of
three cycles of 10 minutes occlusion/reperfusion in pig latis­
simus dorsi muscle flaps with a vascular clamp reduced the
muscle infarction by 40–50% when these muscle flaps were
subsequently subjected to 4 hours of warm ischemia and 48
hours of reperfusion. This observation was confirmed with
pig gracilis muscle flaps in our laboratory.239,240 Subsequently,
other investigators reported that local preischemic condition­
ing also augmented ischemia–reperfusion injury tolerance in
rat skeletal muscle,241–243 and in the skin of cutaneous and
musculocutaneous flaps in the rat.244,245 Local preischemic
preconditioning also attenuated vascular dysfunction in rat
skeletal muscle246 and capillary no-reflow in rat and dog
skeletal muscle induced by sustained ischemia and reperfu­
sion.247,248 However, local preischemic conditioning has clini­
cal limitations because it requires instigation of brief cycles
of ischemia and reperfusion by repeated clamping of the
vascular pedicle and there is the risk of damaging the blood
vessels. However, understanding the mechanism of local
preischemic conditioning may provide insight into the
identification of pharmacological treatment to mimic local
preischemic conditioning. Using pharmacological probes,
we uncovered that the mechanism of local preischemic con­
ditioning in pig latissimus dorsi muscle flaps involved ade­
nosine A1 receptor–protein kinase C–mitochondrial KATP
channel-linked events.249–254 Martou et al. in our laboratory
demonstrated the efficacy of preischemic conditioning
against ischemia–reperfusion injury in ex vivo human rectus
abdominis muscle strips.62 This model is now being used
to study the pharmacological preischemic conditioning
against ischemia–reperfusion injury in ex vivo human skeletal
muscle strips.
Remote preischemic conditioning against
ischemia–reperfusion injury in skeletal muscle
Of interest was the report from Oxman et al. that the instiga­
tion of a 10-minute cycle of occlusion and reperfusion in a
hind limb by tourniquet application preconditioned the heart
against reperfusion tachyarrhythmia in the rat.255 This is
known as remote preischemic conditioning. Based on this
technique, Addison et al. in our laboratory demonstrated for
the first time the efficacy of noninvasive hind limb remote
preischemic conditioning for the global protection of skeletal
muscle against ischemia–reperfusion injury.256 Specifically, we
demonstrated that the instigation of three cycles of 10 minutes
of occlusion/reperfusion in a hind limb of the pig by tourni­
quet application (~300 mmHg) under general anesthesia
protected multiple skeletal muscles at various distant loca­
tions from infarction when these muscles were subsequently
subjected to 4 hours of ischemia and 48 hours of reperfusion
(Fig. 23.6). We also observed that mitochondrial KATP channels
play a central role in the trigger and mediator mechanisms of
hind limb remote preischemic conditioning of pig skeletal
muscle against infarction.257
Fig. 23.6  Noninvasive remote preischemic conditioning for global protection of
skeletal muscle against ischemia–reperfusion injury. Instigation of three cycles of
10 minutes occlusion/reperfusion in a hind limb of the pig by tourniquet application
(~300 mmHg) protected latissimus dorsi, gracilis, and rectus abdominis muscle
flaps from infarction when subsequently subjected to 4 hours of ischemia and 48
hours of reperfusion.
Tourniquet
Fig. 23.7  Biphasic time course of the infarct-protective effect of remote ischemic
conditioning. Muscle flaps in control and treatment groups were subjected to 4
hours of ischemia and 48 hours of reperfusion. In the treatment groups, 4 hours of
ischemia began at 0, 4, 6, 8, 24, 28, 36, 48, 72, or 96 hours after remote ischemic
conditioning. Infarct protection occurred at 0–4 hours and 24–72 hours after remote
ischemic conditioning. Values are mean ± SEM; n = 8 flaps. Means with an
asterisk are similar and are significantly different from the means without an asterisk
(n = 8 flaps, P < 0.05).
*
*
*
*
*
*
*
0
Control
Time after remote ischemic preconditioning
96h
72h
48h
36h
28h
24h
12h
6h
4h
1h
10
Muscle infarction (%)
20
30
40
50
60

442
CHAPTER 23 • Flap pathophysiology and pharmacology
Conclusion and future directions
Flap pathophysiology
Surgical and vascular delay are the only proven clinical
techniques for augmentation of pedicle skin flap viability.
However, these surgical manipulations are time-consuming
and costly. Similarly, preischemic and postischemic condi­
tioning are effective in protecting skeletal muscle flaps
from ischemia–reperfusion injury in laboratory animals, but
surgeons are reticent to conduct a clinical trial on the efficacy
of ischemic preconditioning and postconditioning against
ischemia–reperfusion injury in free flap surgery because
these techniques are invasive and/or time consuming.
Therefore, there is the need to continue to search for phar­
macological therapy to increase skin blood flows and distal
perfusion in pedicle skin flaps and to protect the skin and
muscle from ischemia–reperfusion injury in free flaps and
replant surgery.
Flap pharmacology
The angiogenic cytokine VEGF165 is known to cause local
vasodilation and increases in capillary density (angiogenesis),
resulting in augmentation of skin blood flow and viability in
random pattern skin flaps in the rat. However, review of the
literature thus far indicates that the skin flap viability in
VEGF165 gene or protein therapy was about 15–20% lower
than that of surgical delay.187,197 In addition, angiopoietin-2 is
known to induce arteriogenesis in mouse ischemic hind
limb.274 Therefore, future studies are recommended to inves­
tigate if combined local VEGF165 and angiopoietin-2 protein
or gene therapy will synergistically increase capillary and
arteriole density, resulting in maximizing skin viability in
random skin flaps.
In the cases of ischemic–reperfusion injury in skeletal
muscle, future studies are required to understand the mecha­
nism of preischemic and postischemic conditioning in protect­
ing skeletal muscle against ischemic–reperfusion injury in
laboratory animals in vivo and human skeletal muscle in vitro.
This probably will include studying the role of Na+/H+
exchangers, mitochondrial free Ca2+ content, and opening of
the mPTP in the pathogenesis of ischemia–reperfusion injury.
This area of research will most likely lead to the identification
of pharmacological agents to protect skeletal muscle from
ischemia–reperfusion injury when given before or after ische­
mia. Further studies are also recommended to investigate the
additive effect of combined preischemic and postischemic
pharmacological conditioning to protect skeletal muscle from
ischemia–reperfusion injury. Last but not least, our published
human skeletal muscle strip culture technique62 is recom­
mended for scanning drugs for clinical studies of preischemic
and/or postischemic pharmacological conditioning of skeletal
muscle against ischemia–reperfusion injury.62,272,275
Acknowledgments
The authors thank Dianne McIntyre, and Laura-Anne Male for perform­
ing the word processing and Luke Itani for drawing the figures, respec­
tively, for this manuscript. Cho Y. Pang is the principal investigator of
operating grants from the Canadian Institutes of Health Research (MOP
81149 and MOP 82833).
hours before surgery to achieve 48 hours of uninterrupted
perioperative protection of skeletal muscle from ischemia–
reperfusion injury in elective microsurgery. Recently, we
observed in pigs that the clinical drug nicorandil induced
48h uninterrupted muscle infarct protection 24h after intra­
venous injection.265
Postischemic conditioning for augmentation of free
flap viability
Khiabani and Kerrigan reported that local intra-arterial infu­
sion of the NO donor SIN-1 to pig latissimus dorsi myocut­
aneous flaps and buttock cutaneous flaps by means of a
catheter for 18 hours after 6 hours of ischemia was effective
in salvaging the ischemic skin and muscle from reperfusion
injury.266 However, this technique is too invasive for routine
clinical use. McAllister et al. in our laboratory reported that
instigation of four cycles of 30-second reperfusion/reocclusion
at the onset of reperfusion after 4 hours of ischemia reduced
pig latissimus dorsi muscle flap infarction by ~50%, assessed
at 48 hours of reperfusion.267 This phenomenon is known as
postischemic conditioning and was first demonstrated in dog
myocardium.268 Subsequently, Park et al. demonstrated that
postischemic conditioning also protected contractile function
of rat extensor digitorum longus muscle subjected to 3 hours
of ischemia and 5 days of reperfusion.269 McAllister also
demonstrated that the mechanism of postischemic condition­
ing in pig skeletal muscle involved lowering of mitochondrial
free Ca2+ content, closing of mitochondrial permeability tran­
sitional pores (mPTP), and increase in muscle ATP content.
The infarct-protective effect of postischemic conditioning was
mimicked by intravenous injection of the mPTP opening
inhibitor cyclosporine A (10 mg/kg) at 5 minutes before
reperfusion.267 This observation suggests that cyclosporine A
may be a potential clinical therapeutic agent for salvaging
ischemic replants and muscle free flaps from reperfusion
injury. Mowlavi et al. reported that preischemic or postisch­
emic cyclosporine A treatment (15 mg/kg, orally) increased
rat gracilis muscle viability when subjected to 4 hours of
ischemia and 24 hours of reperfusion.270 However, statistical
significance was achieved in preischemic treatment but not
postischemic treatment. A higher oral dose of cyclosporine A
may be required for postischemic treatment because, accord­
ing to McAllister et al., the effective dose of cyclosporine A for
postischemic conditioning in pig skeletal muscle flap was
10 mg/kg intravenously.267 At the present time, an in vitro
model is being used in our laboratory to study the efficacy
and mechanism of cyclosporine A in salvage of ex vivo
ischemic human rectus abdominis muscle from reperfusion
injury.271,272
Recently, McAllister et al. also reported that preischemic or
postischemic treatment with the Na+/H+ exchanger inhibitor
cariporide (3 mg/kg, intravenously) induced a significant
decrease in mitochondrial free Ca2+ content and infarct size in
pig latissimus dorsi muscle flaps when subsequently subjected
to 4 hours of ischemia and 48 hours of reperfusion.273 This
observation further supports our finding that the mechanism
of postischemic conditioning involves lowering of mitochon­
drial free Ca2+ content and inhibition of opening of the mPTP,
and the mPTP opening inhibitor cyclosporine A is effective in
salvage of ischemic pig skeletal muscle from reperfusion
injury.

443
References
3. Daniel RK, Kerrigan CL. Principles and physiology of skin flap
surgery. In: McCarthy JG, ed. Plastic Surgery. Philadelphia: WB
Saunders; 1990.
46. Baxter GF. The neutrophil as a mediator of myocardial ischemia-
reperfusion injury: time to move on. Basic Res Cardiol. 2002;97:268–
275. Due to its ubiquity in toxicity in the context of reperfusion, the
neutrophil has long been thought to play a key role in ischemia–
reperfusion tissue damage. A thorough review is presented to
demonstrate that this supposition is not as grounded in the literature as
it may initially seem.
62. Martou G, O’Blenes CA, Huang N, et al. Development of an in
vitro model for study of the efficacy of ischemic preconditioning
in human skeletal muscle against ischemia-reperfusion injury. J
Appl Physiol. 2006;101:1335–1342. Ischemic preconditioning has been
shown to improve tolerance to ischemia in animal models. This study
demonstrates a protective effect of hypoxic preconditioning on human
skeletal muscle exposed to reperfusion conditions.
144. Callegari PR, Taylor GI, Caddy CM, et al. An anatomic review of
the delay phenomenon: I. Experimental studies. Plast Reconstr
Surg. 1992;89:397–407, discussion 417–418. This paper presents an
elegant series of experiments demonstrating the arterial basis for the
delay phenomenon. Subjects ranging from tissue expansion as delay
phenomenon to details of delay technique are addressed.
150. Lineaweaver WC, Lei MP, Mustain W, et al. Vascular endothelium
growth factor, surgical delay, and skin flap survival. Ann Surg.
2004;239:866–873, discussion 873–875. It has previously been
demonstrated that VEGF administration enhances skin flap survival in
an animal model. VEGF is implicated as a possible mediator of
pharmacologic delay in this study, which shows surgical delay to increase
VEGF expression and skin flap survival.
197. Huang N, Khan A, Ashrafpour H, et al. Efficacy and mechanism
of adenovirus-mediated VEGF-165 gene therapy for augmentation
of skin flap viability. Am J Physiol Heart Circ Physiol.
2006;291:H127–H137.
256. Addison PD, Neligan PC, Ashrafpour H, et al. Noninvasive
remote ischemic preconditioning for global protection of skeletal
muscle against infarction. Am J Physiol Heart Circ Physiol.
2003;285:H1435–H1443. This animal study demonstrates that
tourniquet-based ischemic preconditioning protects against distal
muscle against infarction. Direct antagonism was employed to
implicate opioid receptor activation as a mechanism for this
phenomenon.
258. Moses MA, Addison PD, Neligan PC, et al. Inducing late phase of
infarct protection in skeletal muscle by remote preconditioning:
efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol.
2005;289:R1609–R1617.
267. McAllister SE, Ashrafpour H, Cahoon N, et al. Postconditioning
for salvage of ischemic skeletal muscle from reperfusion injury:
efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol.
2008;295:R681–R689.
273. McAllister SE, Moses MA, Jindal K, et al. Na+/H+ exchange
inhibitor cariporide attenuates skeletal muscle infarction when
administered before ischemia or reperfusion. J Appl Physiol.
2009;106:20–28.
Access the complete reference list online at

443.e1
References
References
1. Grabb WMM. Basic techniques of plastic surgery. In: Grabb WC,
Smith JW, eds. Plastic Surgery. Boston: Little Brown; 1979.
2. Manktelow RT. Microvascular Reconstruction: Anatomy, Application
and Surgical Technique. New York: Springer-Verlag; 1987.
3. Daniel RK, Kerrigan CL. Principles and physiology of skin flap
surgery. In: McCarthy JG, ed. Plastic Surgery. Philadelphia: WB
Saunders; 1990.
4. Mathes SJ, Nahai F. Reconstructive Surgery: Principles, Anatomy and
Technique. St. Louis: QMP and Churchill Livingstone; 1997.
5. Schusterman MA, Miller MJ, Reece GP, et al. A single center’s
experience with 308 free flaps for repair of head and neck cancer
defects. Plast Reconstr Surg. 1994;93:472–478, discussion 479–480.
6. Nakatsuka T, Harii K, Yamada A, et al. Versatility of a free inferior
rectus abdominis flap for head and neck reconstruction: analysis of
200 cases. Plast Reconstr Surg. 1994;93:762–769.
7. Malata CM, Cooter RD, Batchelor AG, et al. Microvascular
free-tissue transfers in elderly patients: the leeds experience. Plast
Reconstr Surg. 1996;98:1234–1241.
8. Khouri RK, Cooley BC, Kunselman AR, et al. A prospective study
of microvascular free-flap surgery and outcome. Plast Reconstr
Surg. 1998;102:711–721.
9. Serletti JM, Higgins JP, Moran S, et al. Factors affecting outcome in
free-tissue transfer in the elderly. Plast Reconstr Surg.
2000;106:66–70.
10. Afridi NS, Paletz JL, Morris SF. Free flap failures: what to do next?
Can J Plast Surg. 2000;8:30–32.
11. Weinzweig N, Gonzalez M. Free tissue failure is not an all-or-none
phenomenon. Plast Reconstr Surg. 1995;96:648–660.
12. Yan XQ, Yang HY, Zhao YM, et al. Deep inferior epigastric
perforator flap for breast reconstruction: experience with 43 flaps.
Chin Med J. 2007;120:380–384.
13. Sailon AM, Schachar JS, Levine JP. Free transverse rectus
abdominis myocutaneous and deep inferior epigastric perforator
flaps for breast reconstruction: a systematic review of flap
complication rates and donor-site morbidity. Ann Plast Surg.
2009;62:560–563.
14. Serletti JM, Moran SL. Free versus the pedicled TRAM flap: a cost
comparison and outcome analysis. Plast Reconstr Surg.
1997;100:1418–1424, discussion 1425–1427.
15. Heinz TR, Cowper PA, Levin LS. Microsurgery costs and outcome.
Plast Reconstr Surg. 1999;104:89–96.
16. Rubanyi GM. Endothelium-derived vasoactive factors in health and
disease. Cardiovascular significance of endothelium-derived vasoactive
factors. New York: Future; 1991:xi.
17. Shepherd JT, Vanhoutte PM. Endothelium derived relaxing (EDRF)
and contracting factors (EDCF) in the control of cardiovascular
homeostasis: the pioneering observation. Cardiovascular Significance of
Endothelium-Derived Vascular Factors. New York: Future; 1991:39.
18. Weller R. Nitric oxide – a newly discovered chemical transmitter
in human skin. Br J Dermatol. 1997;137:665–672.
19. Vanhoutte PM. Endothelial control of vasomotor function: from
health to coronary disease. Circ J. 2003;67:572–575.
20. Singel DJ, Stamler JS. Chemical physiology of blood flow
regulation by red blood cells: the role of nitric oxide and
S-nitrosohemoglobin. Annu Rev Physiol. 2005;67:99–145.
21. Guyton AC, Hall JE. Textbook of Medical Physiology. Missouri:
Saunders Elsevier; 2006:195.
22. Blaisdell FW, Steele M, Allen RE. Management of acute lower
extremity arterial ischemia due to embolism and thrombosis.
Surgery. 1978;84:822–834.
23. May JW Jr, Gallico GG 3rd. Upper extremity replantation. Curr
Probl Surg. 1980;17:633–717.
24. Sjostrom M, Neglen P, Friden J, Eklof B. Human skeletal muscle
metabolism and morphology after temporary incomplete
ischaemia. Eur J Clin Invest. 1982;12:69–79.
25. Eckert P, Schnackerz K. Ischemic tolerance of human skeletal
muscle. Ann Plast Surg. 1991;26:77–84.
26. Rutherford RB. Nutrient bed protection during lower extremity
arterial reconstruction. J Vasc Surg. 1987;5:529–534.
27. McCord JM. Oxygen-derived radicals: a link between reperfusion
injury and inflammation. Fed Proc. 1987;46:2402–2406.
28. Korthius RJ, Granger DN. Ischemia-reperfusion injury: role of
oxygen-derived free radicals. In: Taylor AE, Matalon S, Ward PA,
eds. Physiology of Oxygen Radicals. Bethesda, MD: American
Physiological Society; 1986:217.
29. Granger DN. Role of xanthine oxidase and granulocytes in
ischemia-reperfusion injury. Am J Physiol. 1988;255:H1269–
H1275.
30. Singal OK, Grepta M. Role of free radicals in drug-induced
myocardial effects. In: Miguel J, Quintanilha AT, Heber H, eds.
CRC Handbook of Free Radicals and Antioxidants in Biomedicine. Boca
Raton, Florida: CRC Press; 1989:287.
31. Grisham MB. Chemistry and cytotoxicity of reactive oxygen
metabolite. In: Taylor AE, Matalon S, Ward PA, eds. Physiology of
Oxygen Radicals. Bethesda, MD: American Physiological Society;
1986:1.
32. Im MJ, Hoopes JE, Yoshimura Y, et al. Xanthine:acceptor
oxidoreductase activities in ischemic rat skin flaps. J Surg Res.
1989;46:230–234.
33. Im MJ, Shen WH, Pak CJ, et al. Effect of allopurinol on the
survival of hyperemic island skin flaps. Plast Reconstr Surg.
1984;73:276–278.
34. Smith JK, Carden DL, Korthuis RJ. Role of xanthine oxidase in
postischemic microvascular injury in skeletal muscle. Am J Physiol.
1989;257:H1782–H1789.
35. Picard-Ami LA Jr, MacKay A, Kerrigan CL. Pathophysiology of
ischemic skin flaps: differences in xanthine oxidase levels among
rats, pigs, and humans. Plast Reconstr Surg. 1991;87:750–755.
36. Picard-Ami LA Jr, MacKay A, Kerrigan CL. Effect of allopurinol on
the survival of experimental pig flaps. Plast Reconstr Surg.
1992;89:1098–1103.
37. Dorion D, Zhong A, Chiu C, et al. Role of xanthine oxidase in
reperfusion injury of ischemic skeletal muscles in the pig and
human. J Appl Physiol. 1993;75:246–255.
38. Thomas EL, Grisham MB, Jefferson MM. Myeloperoxidase-
dependent effect of amines on functions of isolated neutrophils.
J Clin Invest. 1983;72:441–454.
39. Grisham MB, Jefferson MM, Melton DF, et al. Chlorination of
endogenous amines by isolated neutrophils. Ammonia-dependent
bactericidal, cytotoxic, and cytolytic activities of the chloramines. J
Biol Chem. 1984;259:10404–10413.
40. Grisham MB, Jefferson MM, Thomas EL. Role of monochloramine
in the oxidation of erythrocyte hemoglobin by stimulated
neutrophils. J Biol Chem. 1984;259:6757–6765.
41. Vedder NB, Winn RK, Rice CL, et al. Inhibition of leukocyte
adherence by anti-CD18 monoclonal antibody attenuates
reperfusion injury in the rabbit ear. Proc Natl Acad Sci USA.
1990;87:2643–2646.
42. Tosa Y, Lee WP, Kollias N, et al. Monoclonal antibody to
intercellular adhesion molecule 1 protects skin flaps against
ischemia-reperfusion injury: an experimental study in rats. Plast
Reconstr Surg. 1998;101:1586–1594, discussion 1595–1596.
43. Stotland MA, Kerrigan CL. E- and L-selectin adhesion molecules
in musculocutaneous flap reperfusion injury. Plast Reconstr Surg.
1997;99:2010–2020.
44. Zamboni WA, Stephenson LL, Roth AC, et al. Ischemia-reperfusion
injury in skeletal muscle: CD 18-dependent neutrophil-endothelial
adhesion and arteriolar vasoconstriction. Plast Reconstr Surg.
1997;99:2002–2007, discussion 2008–2009.
45. Korthuis RJ, Grisham MB, Granger DN. Leukocyte depletion
attenuates vascular injury in postischemic skeletal muscle. Am J
Physiol. 1988;254:H823–H827.
46. Baxter GF. The neutrophil as a mediator of myocardial ischemia-
reperfusion injury: time to move on. Basic Res Cardiol. 2002;97:268–
275. Due to its ubiquity in toxicity in the context of reperfusion, the
neutrophil has long been thought to play a key role in ischemia–
reperfusion tissue damage. A thorough review is presented to

443.e2
CHAPTER 23 • Flap pathophysiology and pharmacology
demonstrate that this supposition is not as grounded in the literature as
it may initially seem.
47. Lefer DJ. Do neutrophils contribute to myocardial reperfusion
injury? Basic Res Cardiol. 2002;97:263–267.
48. Vinten-Johansen J. Involvement of neutrophils in the pathogenesis
of lethal myocardial reperfusion injury. Cardiovasc Res.
2004;61:481–497.
49. Sun HY, Wang NP, Kerendi F, et al. Hypoxic postconditioning
reduces cardiomyocyte loss by inhibiting ROS generation and
intracellular Ca2+ overload. Am J Physiol Heart Circ Physiol.
2005;288:H1900–H1908.
50. Zhang JG, Ghosh S, Ockleford CD, et al. Characterization of an in
vitro model for the study of the short and prolonged effects of
myocardial ischaemia and reperfusion in man. Clin Sci.
2000;99:443–453.
51. Shanmuganathan S, Hausenloy DJ, Duchen MR, et al.
Mitochondrial permeability transition pore as a target for
cardioprotection in the human heart. Am J Physiol Heart Circ
Physiol. 2005;289:H237–H242.
52. Miyamae M, Camacho SA, Weiner MW, et al. Attenuation of
postischemic reperfusion injury is related to prevention of
[Ca2+]m overload in rat hearts. Am J Physiol. 1996;271:
H2145–H2153.
53. Darling CE, Jiang R, Maynard M, et al. Postconditioning via
stuttering reperfusion limits myocardial infarct size in rabbit
hearts: role of ERK1/2. Am J Physiol Heart Circ Physiol.
2005;289:H1618–H1626.
54. Przyklenk K, Maynard M, Darling CE, et al. Aging mouse hearts
are refractory to infarct size reduction with post-conditioning. J
Am Coll Cardiol. 2008;51:1393–1398.
55. Flaherty JT, Pitt B, Gruber JW, et al. Recombinant human
superoxide dismutase (h-SOD) fails to improve recovery of
ventricular function in patients undergoing coronary angioplasty
for acute myocardial infarction. Circulation. 1994;89:1982–1991.
56. Tsujita K, Shimomura H, Kawano H, et al. Effects of edaravone on
reperfusion injury in patients with acute myocardial infarction. Am
J Cardiol. 2004;94:481–484.
57. Perez RG, Arai M, Richardson C, et al. Factors modifying
protective effect of anti-CD18 antibodies on myocardial
reperfusion injury in dogs. Am J Physiol. 1996;270:H53–H64.
58. Zhao ZQ, Lefer DJ, Sato H, et al. Monoclonal antibody to ICAM-1
preserves postischemic blood flow and reduces infarct size after
ischemia-reperfusion in rabbit. J Leukoc Biol. 1997;62:292–300.
59. Baran KW, Nguyen M, McKendall GR, et al. Double-blind,
randomized trial of an anti-CD18 antibody in conjunction with
recombinant tissue plasminogen activator for acute myocardial
infarction: limitation of myocardial infarction following
thrombolysis in acute myocardial infarction (LIMIT AMI) study.
Circulation. 2001;104:2778–2783.
60. Rusnak JM, Kopecky SL, Clements IP, et al. An anti-CD11/CD18
monoclonal antibody in patients with acute myocardial infarction
having percutaneous transluminal coronary angioplasty (the
FESTIVAL study). Am J Cardiol. 2001;88:482–487.
61. Faxon DP, Gibbons RJ, Chronos NA, et al. The effect of blockade
of the CD11/CD18 integrin receptor on infarct size in patients
with acute myocardial infarction treated with direct angioplasty:
the results of the HALT-MI study. J Am Coll Cardiol.
2002;40:1199–1204.
62. Martou G, O’Blenes CA, Huang N, et al. Development of an in
vitro model for study of the efficacy of ischemic preconditioning
in human skeletal muscle against ischemia-reperfusion injury. J
Appl Physiol. 2006;101:1335–1342. Ischemic preconditioning has been
shown to improve tolerance to ischemia in animal models. This study
demonstrates a protective effect of hypoxic preconditioning on human
skeletal muscle exposed to reperfusion conditions.
63. Murphy E, Cross HR, Steenbergen C. Na+/H+ and Na+/Ca2+
exchange: their role in the rise in cytosolic free (Ca2+) during
ischemia and reperfusion. Eur Heart J. 1999;(suppl K):K18–K30.
64. Dennis SC, Gevers W, Opie LH. Protons in ischemia: where do
they come from; where do they go to? J Mol Cell Cardiol.
1991;23:1077–1086.
65. Frelin C, Vigne P, Lazdunski M. The role of the Na+/H+ exchange
system in cardiac cells in relation to the control of the internal Na+
concentration. A molecular basis for the antagonistic effect of
ouabain and amiloride on the heart. J Biol Chem.
1984;259:8880–8885.
66. Lazdunski M, Frelin C, Vigne P. The sodium/hydrogen exchange
system in cardiac cells: its biochemical and pharmacological
properties and its role in regulating internal concentrations of
sodium and internal pH. J Mol Cell Cardiol. 1985;17:1029–1042.
67. Tani M, Neely JR. Role of intracellular Na+ in Ca2+ overload and
depressed recovery of ventricular function of reperfused ischemic
rat hearts. Possible involvement of H+-Na+ and Na+-Ca2+
exchange. Circ Res. 1989;65:1045–1056.
68. Tani M, Neely JR. Na+ accumulation increases Ca2+ overload and
impairs function in anoxic rat heart. J Mol Cell Cardiol.
1990;22:57–72.
69. Doering AE, Lederer WJ. The mechanism by which cytoplasmic
protons inhibit the sodium-calcium exchanger in guinea-pig heart
cells. J Physiol. 1993;466:481–499.
70. Yao A, Su Z, Nonaka A, et al. Effects of overexpression of the
Na+-Ca2+ exchanger on [Ca2+]i transients in murine ventricular
myocytes. Circ Res. 1998;82:657–665.
71. Toda T, Kadono T, Hoshiai M, et al. Na+/H+ exchanger inhibitor
cariporide attenuates the mitochondrial Ca2+ overload and PTP
opening. Am J Physiol Heart Circ Physiol. 2007;293:H3517–H3523.
72. Yan GX, Kleber AG. Changes in extracellular and intracellular
pH in ischemic rabbit papillary muscle. Circ Res. 1992;71:
460–470.
73. Vaughan-Jones RD, Wu ML. Extracellular H+ inactivation of
Na(+)-H+ exchange in the sheep cardiac Purkinje fibre. J Physiol.
1990;428:441–466.
74. du Toit EF, Opie LH. Modulation of severity of reperfusion
stunning in the isolated rat heart by agents altering calcium flux at
onset of reperfusion. Circ Res. 1992;70:960–967.
75. May JW Jr, Chait LA, O’Brien BM, et al. The no-reflow
phenomenon in experimental free flaps. Plast Reconstr Surg.
1978;61:256–267.
76. Allen DM, Chen LE, Seaber AV, et al. Pathophysiology and related
studies of the no reflow phenomenon in skeletal muscle. Clin
Orthop Relat Res. 1995;314:122–133.
77. Milton SH. Pedicled skin-flaps: the fallacy of the length: width
ratio. Br J Surg. 1970;57:502–508.
78. Daniel RK. The anatomy and hemodynamics of the cutaneous
circulation and their influence on skin flap design. In: Grabb WC,
Myers MB, eds. Skin Flaps. Boston: Little, Brown; 1975:111.
79. Kaplan EN, Knapp TR. Flap design: the anatomical and
physiological bases. In: Kernaban DA, Visntes CM, eds. Biological
Aspects of Reconstructive Surgery. Boston, Massachusetts: Little,
Brown; 1977:241–263.
80. Hartrampf CR, Scheflan M, Black PW. Breast reconstruction with a
transverse abdominal island flap. Plast Reconstr Surg.
1982;69:216–225.
81. Jensen JA, Handel N, Silverstein MJ, et al. Extended skin island
delay of the unipedicle TRAM flap: experience in 35 patients. Plast
Reconstr Surg. 1995;96:1341–1345.
82. Codner MA, Bostwick J 3rd, Nahai F, et al. TRAM flap vascular
delay for high-risk breast reconstruction. Plast Reconstr Surg.
1995;96:1615–1622.
83. Ribuffo D, Muratori L, Antoniadou K, et al. A hemodynamic
approach to clinical results in the TRAM flap after selective delay.
Plast Reconstr Surg. 1997;99:1706–1714.
84. O’Shaughnessy KD, Mustoe TA. The surgical TRAM flap delay:
reliability of zone III using a simplified technique under local
anesthesia. Plast Reconstr Surg. 2008;122:1627–1630.
85. Mcfarlane RM, Deyoung G, Henry RA. The Design of a Pedicle
Flap in the Rat to Study Necrosis and its Prevention. Plast Reconstr
Surg. 1965;35:177–182.
86. Myers MB, Cherry G. Augmentation of tissue survival by delay:
an experimental study in rabbits. Plast Reconstr Surg.
1967;39:397–401.

443.e3
References
87. Myers MB, Cherry G. Differences in the delay phenomenon in the
rabbit, rat, and pig. Plast Reconstr Surg. 1971;47:73–78.
88. Forrest CR, Pang CY, Zhong AG, et al. Role of noradrenaline in the
pathogenesis of skin flap ischemic necrosis in the pig. J Surg Res.
1990;48:237–244.
89. Boyd JB, Markland B, Dorion D, et al. Surgical augmentation of
skin blood flow and viability in a pig musculocutaneous flap
model. Plast Reconstr Surg. 1990;86:731–738.
90. Dorion D, Boyd JB, Pang CY. Augmentation of transmidline skin
perfusion and viability in transverse rectus abdominis
myocutaneous (TRAM) flaps in the pig. Plast Reconstr Surg.
1991;88:642–649.
91. Ozgentas HE, Shenaq S, Spira M. Study of the delay phenomenon
in the rat TRAM flap model. Plast Reconstr Surg. 1994;94:1018–
1024, discussion 1025–1026.
92. Hallock GG, Rice DC. Evidence for the efficacy of TRAM flap
delay in a rat model. Plast Reconstr Surg. 1995;96:1351–1357.
93. Barker JH, van Aalst VC, Keelen PC, et al. Vascular delay in
skeletal muscle: a model for microcirculatory studies. Plast
Reconstr Surg. 1997;100:665–669.
94. Restifo RJ, Ahmed SS, Rosser J, et al. TRAM flap perforator
ligation and the delay phenomenon: development of an
endoscopic/laparoscopic delay procedure. Plast Reconstr Surg.
1998;101:1503–1511.
95. Morris SF, Yang D. Effect of vascular delay on viability,
vasculature, and perfusion of muscle flaps in the rabbit. Plast
Reconstr Surg. 1999;104:1041–1047.
96. Wan C, Maldonado C, Papanicolaou G, et al. Reducing the
vascular delay period in latissimus dorsi muscle flaps for use in
cardiomyoplasty. Plast Reconstr Surg. 2002;109:1630–1637.
97. Wong MS, Erdmann D, Sweis R, et al. Basic fibroblast growth
factor expression following surgical delay of rat transverse rectus
abdominis myocutaneous flaps. Plast Reconstr Surg.
2004;113:2030–2036.
98. Seyhan T, Deniz M, Borman H, et al. Comparison of two different
vascular delay methods in a rat cranial epigastric perforator flap
model. Ann Plast Surg. 2010;64:89–92.
99. Bakamjian VY. The deltopectoral flap. In: Grabb WC, Smith JW,
eds. Skin Flaps. Boston, Massachusetts: Little, Brown; 1975:
225–258.
100. Guba AM Jr. Arteriovenous shunting in the pig. Plast Reconstr
Surg. 1980;65:323–327.
101. Pang CY, Forrest CR, Neligan PC, et al. Augmentation of blood
flow in delayed random skin flaps in the pig: effect of length of
delay period and angiogenesis. Plast Reconstr Surg. 1986;78:68–74.
102. Restifo RJ, Ward BA, Scoutt LM, et al. Timing, magnitude, and
utility of surgical delay in the TRAM flap: II. Clinical studies. Plast
Reconstr Surg. 1997;99:1217–1223.
103. Restifo RJ, Syed SA, Ward BA, et al. Surgical delay in TRAM flap
breast reconstruction: a comparison of 7- and 14-day delay
periods. Ann Plast Surg. 1997;38:330–333, discussion 333–334.
104. Scheufler O, Andresen R, Kirsch A, et al. Clinical results of TRAM
flap delay by selective embolization of the deep inferior epigastric
arteries. Plast Reconstr Surg. 2000;105:1320–1329.
105. Berrino P, Santi P. Hemodynamic analysis of the TRAM.
Applications to the “recharged” TRAM flap. Clin Plast Surg.
1994;21:233–245.
106. Holmstrom H. The free abdominoplasty flap and its use in breast
reconstruction. An experimental study and clinical case report.
Scand J Plast Reconstr Surg. 1979;13:423–427.
107. Friedman RJ, Argenta LC, Anderson R. Deep inferior epigastric
free flap for breast reconstruction after radical mastectomy. Plast
Reconstr Surg. 1985;76:455–460.
108. Grotting JC, Urist MM, Maddox WA, et al. Conventional TRAM
flap versus free microsurgical TRAM flap for immediate breast
reconstruction. Plast Reconstr Surg. 1989;83:828–841, discussion
842–844.
109. Yamada A, Harii K, Hirabayashi S, et al. Breast reconstruction with
the free TRAM flap after breast cancer surgery. J Reconstr
Microsurg. 1992;8:1–6, discussion 7–8.
110. Banic A, Boeckx W, Greulich M, et al. Late results of breast
reconstruction with free TRAM flaps: a prospective multicentric
study. Plast Reconstr Surg. 1995;95:1195–1204, discussion 1205–1206.
111. Reinisch JF. The pathophysiology of skin flap circulation. The
delay phenomenon. Plast Reconstr Surg. 1974;54:585–598.
112. Pearl RM. A unifying theory of the delay phenomenon–recovery
from the hyperadrenergic state. Ann Plast Surg. 1981;7:102–112.
113. Prather A, Blackburn JP, Williams TR, et al. Evaluation of tests for
predicting the viability of axial pattern skin flaps in the pig. Plast
Reconstr Surg. 1979;63:250–257.
114. Palmer B. Sympathetic denervation and reinnervation of
cutaneous blood vessels following surgery. An experimental study
on rats by means of a histochemical fluorescence method. Scand J
Plast Reconstr Surg. 1970;4:93–99.
115. Cutting CB, Robson MC, Koss N. Denervation supersensitivity
and the delay phenomenon. Plast Reconstr Surg. 1978;61:
881–887.
116. Cutting C, Bumsted R, Bardach J, et al. Changes in quantitative
norepinephrine levels in delayed pig flank flaps. Plast Reconstr
Surg. 1982;69:652–655.
117. Kerrigan CL. Skin flap failure: pathophysiology. Plast Reconstr
Surg. 1983;72:766–777.
118. Pang CY, Neligan PC, Forrest CR, et al. Hemodynamics and
vascular sensitivity to circulating norepinephrine in normal skin
and delayed and acute random skin flaps in the pig. Plast Reconstr
Surg. 1986;78:75–84.
119. Sasaki GH, Pang CY. Hemodynamics and viability of acute
neurovascular island skin flaps in rats. Plast Reconstr Surg.
1980;65:152–158.
120. Kreidstein ML, Zacks SL, Pang CY. Study of the microcirculation
in the isolated perfused human skin flap model. Surg For.
1990;41:664–666.
121. Jurell G, Hjemdahl P. Degeneration release of noradrenaline in
skin flaps in rats. Acta Physiol Scand. 1981;113:285–289.
122. Hendel PM, Lilien DL, Buncke HJ. A study of the pharmacologic
control of blood flow to delayed skin flaps using xenon washout.
Part II. Plast Reconstr Surg. 1983;71:399–407.
123. Jurell G, Hjemdahl P, Fredholm BB. On the mechanism by which
antiadrenergic drugs increase survival of critical skin flaps. Plast
Reconstr Surg. 1983;72:518–525.
124. Edstrom LE, Balkovich M, Slotman GJ. Effect of ischemic skin flap
elevation on tissue and plasma thromboxane A2 and prostacyclin
production: modification by thromboxane synthetase inhibition.
Ann Plast Surg. 1988;20:106–111.
125. Jurell G. Adrenergic nerves and the delay phenomenon. Ann Plast
Surg. 1986;17:493–497.
126. Angel MF, Knight KR, Mellow CG, et al. The effect of prior
elevation of skin flaps and ischemia on blood thromboxane levels.
Ann Plast Surg. 1989;22:501–504.
127. Samuelson UE, Heden P, Jernbeck J, et al. Endothelin reduces
blood flow in experimental skin flaps. Scand J Plast Reconstr Surg
Hand Surg. 1992;26:241–245.
128. Matsuzaki K. Effect of skin flap ischemia on plasma endothelin-1
levels. Ann Plast Surg. 1993;31:499–503.
129. Tane N, Inoue H, Aihara M, et al. The effects of endothelin-1 on
flap necrosis. Ann Plast Surg. 1995;35:389–395.
130. Tuominen HP, Svartling NE, Tikkanen IT, et al. Perioperative
plasma endothelin-1 concentrations and vasoconstriction during
prolonged plastic surgical procedures. Br J Anaesth.
1995;74:661–666.
131. Pang CY, Chiu C, Zhong A, Xu N. Pharmacologic intervention of
skin vasospasm and ischemic necrosis in pigs. J Cardiovasc
Pharmacol. 1993;21:163–171.
132. He W, Neligan P, Lipa J, et al. Comparison of secondary ischemic
tolerance between pedicled and free island buttock skin flaps
in the pig. Plast Reconstr Surg. 1997;100:72–81, discussion
82–83.
133. Inoue H, Aihara M, Tomioka M, et al. Changes in endothelin-1,
6-keto-PG-F1 alpha, and TX-B2 in random pattern flaps. J
Cardiovasc Pharmacol. 1998;31(suppl 1):S477–S479.

443.e4
CHAPTER 23 • Flap pathophysiology and pharmacology
134. Pang CY, Xu H, Huang N, et al. Amplification effect and
mechanism of action of ET-1 in U-46619-induced vasoconstriction
in pig skin. Am J Physiol Regul Integr Comp Physiol.
2001;280:R713–R720.
135. Lantieri LA, Carayon A, Maistre O, et al. Tissue and plasma
levels of endothelin in free flaps. Plast Reconstr Surg.
2003;111:85–91.
136. Kreidstein ML, Pang CY, Levine RH, et al. The isolated perfused
human skin flap: design, perfusion technique, metabolism, and
vascular reactivity. Plast Reconstr Surg. 1991;87:741–749.
137. Kreidstein ML, Pang CY, Carlsen LN, et al. Evidence for
endothelium-dependent and endothelium-independent
vasodilation in human skin flaps. Can J Physiol Pharmacol.
1992;70:1208–1216.
138. Zhang J, Lipa JE, Black CE, et al. Pharmacological characterization
of vasomotor activity of human musculocutaneous perforator
artery and vein. J Appl Physiol. 2000;89:2268–2275.
139. Pang CY, Yang RZ, Neligan P, et al. Vascular effects and
mechanism of action of endothelin-1 in isolated perfused pig skin.
J Appl Physiol. 1995;79:2106–2113.
140. Pang CY, Zhang J, Xu H, et al. Role and mechanism of
endothelin-B receptors in mediating ET-1-induced vasoconstriction
in pig skin. Am J Physiol. 1998;275:R1066–R1074.
141. Lipa JE, Neligan PC, Perreault TM, et al. Vasoconstrictor effect of
endothelin-1 in human skin: role of ETA and ETB receptors. Am J
Physiol. 1999;276:H359–H367.
142. Black CE, Huang N, Neligan PC, et al. Effect of nicotine on
vasoconstrictor and vasodilator responses in human skin
vasculature. Am J Physiol Regul Integr Comp Physiol.
2001;281:R1097–R1104.
143. Black CE, Huang N, Neligan PC, et al. Vasoconstrictor effect and
mechanism of action of endothelin-1 in human radial artery and
vein: implication of skin flap vasospasm. J Cardiovasc Pharmacol.
2003;41:460–467.
144. Callegari PR, Taylor GI, Caddy CM, et al. An anatomic review of
the delay phenomenon: I. Experimental studies. Plast Reconstr
Surg. 1992;89:397–407, discussion 417–418. This paper presents an
elegant series of experiments demonstrating the arterial basis for the
delay phenomenon. Subjects ranging from tissue expansion as delay
phenomenon to details of delay technique are addressed.
145. Taylor GI, Corlett RJ, Caddy CM, et al. An anatomic review of the
delay phenomenon: II. Clinical applications. Plast Reconstr Surg.
1992;89:408–416, discussion 417–418.
146. Morris SF, Taylor GI. Predicting the survival of experimental skin
flaps with a knowledge of the vascular architecture. Plast Reconstr
Surg. 1993;92:1352–1361.
147. Dhar SC, Taylor GI. The delay phenomenon: the story unfolds.
Plast Reconstr Surg. 1999;104:2079–2091.
148. Yang D, Morris SF. Comparison of two different delay procedures
in a rat skin flap model. Plast Reconstr Surg. 1998;102:1591–1597.
149. Yang D, Morris SF. An extended dorsal island skin flap with
multiple vascular territories in the rat: a new skin flap model. J
Surg Res. 1999;87:164–170.
150. Lineaweaver WC, Lei MP, Mustain W, et al. Vascular endothelium
growth factor, surgical delay, and skin flap survival. Ann Surg.
2004;239:866–873, discussion 873–875. It has previously been
demonstrated that VEGF administration enhances skin flap survival in
an animal model. VEGF is implicated as a possible mediator of
pharmacologic delay in this study, which shows surgical delay to increase
VEGF expression and skin flap survival.
151. Dobryansky M, Galiano RD, Cetrulo CL Jr, et al. Endostatin
inhibits ischemia-induced neovascularization and increases
ischemic tissue loss. Ann Plast Surg. 2004;52:512–518, discussion
518.
152. Pang CY, Forrest CR, Morris SF. Pharmacological augmentation of
skin flap viability: a hypothesis to mimic the surgical delay
phenomenon or a wishful thought. Ann Plast Surg.
1989;22:293–306.
153. Pang CY. Ischemia-induced reperfusion injury in muscle flaps:
pathogenesis and major source of free radicals. J Reconstr
Microsurg. 1990;6:77–83.
154. Hira M, Tajima S, Sano S. Increased survival length of
experimental flap by calcium antagonist nifedipine. Ann Plast
Surg. 1990;24:45–48.
155. Emery FM, Kodey TR, Bomberger RA, et al. The effect of
nifedipine on skin-flap survival. Plast Reconstr Surg. 1990;85:61–63.
156. Knight KR, Kawabata H, Coe SA, et al. Prostacyclin and
prostanoid modifiers aid ischemic skin flap survival. J Surg Res.
1991;50:119–123.
157. Galla TJ, Saetzler RK, Hammersen F, et al. Increase in skin-flap
survival by the vasoactive drug buflomedil. Plast Reconstr Surg.
1991;87:130–136, discussion 137–138.
158. Matsuo K, Kushima H, Noguchi M, et al. Continuous intraarterial
infusion of prostaglandin E1 and heparin to extend and improve
the survival of pedicled musculocutaneous flaps through unusual
routes: a clinical preliminary report. Ann Plast Surg.
1992;29:314–320.
159. Suarez Nieto C, Suarez Garcia MJ, Barthe Garcia P. A comparative
study on the effect of various pharmacological agents on the
survival of skin flaps in the rat. Br J Plast Surg. 1992;45:113–116.
160. Okamoto Y, Nakajima T, Yoneda K. Augmentation of skin flap
survival by selective intraarterial infusion of prostaglandin E1:
experimental and clinical studies. Ann Plast Surg. 1993;30:
154–158.
161. Price MA, Pearl RM. Multiagent pharmacotherapy to enhance skin
flap survival: lack of additive effect of nitroglycerin and
allopurinol. Ann Plast Surg. 1994;33:52–56.
162. Senderoff DM, Israeli D, Zhang WX, et al. Iloprost improves
survival of ischemic experimental skin flaps. Ann Plast Surg.
1994;32:490–495.
163. Kuwahara H, Fazhi Q, Sugihara T, et al. The effects of lipo-
prostaglandin E1 on axial pattern flaps in rabbits. Ann Plast Surg.
1995;35:620–626.
164. Asai S, Fukuta K, Torii S. Topical administration of prostaglandin
E1 with iontophoresis for skin flap viability. Ann Plast Surg.
1997;38:514–517.
165. Komorowska-Timek E, Chen SG, Zhang F, et al. Prolonged
perivascular use of verapamil or lidocaine decreases skin flap
necrosis. Ann Plast Surg. 1999;43:283–288.
166. Hong JP, Chung YK, Chung SH. The effect of prostaglandin E1
versus ischemia-reperfusion injury of musculocutaneous flaps.
Ann Plast Surg. 2001;47:316–321.
167. Komorowska-Timek E, Timek TA, Brevetti LS, et al. Oral
administration of L-arginine decreases necrosis of the epigastric
skin flap in the rat. Ann Plast Surg. 2004;53:73–78.
168. Um SC, Suzuki S, Toyokuni S, et al. Involvement of nitric oxide in
survival of random pattern skin flap. Plast Reconstr Surg.
1998;101:785–792.
169. Huemer GM, Wechselberger G, Otto-Schoeller A, et al. Improved
dorsal random-pattern skin flap survival in rats with a topically
applied combination of nonivamide and nicoboxil. Plast Reconstr
Surg. 2003;111:1207–1211.
170. Engel H, Sauerbier M, Germann G, et al. Dose-dependent effects
of a nitric oxide donor in a rat flap model. Ann Plast Surg.
2007;58:456–460.
171. Ono I, Ohura T, Murazumi M, et al. A study on the effectiveness
of a thromboxane synthetase inhibitor (OKY-046) in increasing the
survival length of skin flaps. Plast Reconstr Surg. 1990;86:1164–1173.
172. Vedder NB, Bucky LP, Richey NL, et al. Improved survival rates of
random flaps in rabbits with a monoclonal antibody that blocks
leukocyte adherence. Plast Reconstr Surg. 1994;93:1035–1040.
173. Nakatsuka T, Pang CY, Neligan P, et al. Effect of glucocorticoid
treatment on skin capillary blood flow and viability in cutaneous
and myocutaneous flaps in the pig. Plast Reconstr Surg.
1985;76:374–385.
174. Pang CY, Neligan PC, Nakatsuka T, et al. Pharmacologic
manipulation of the microcirculation in cutaneous and
myocutaneous flaps in pigs. Clin Plast Surg. 1985;12:173–184.
175. Neligan P, Pang CY, Nakatsuka T, et al. Pharmacologic action of
isoxsuprine in cutaneous and myocutaneous flaps. Plast Reconstr
Surg. 1985;75:363–374.

443.e5
References
176. Forrest CR, Pang CY, Zhong AG, et al. Efficacy of intravenous
infusion of prostacyclin (PGI2) or prostaglandin E1 (PGE1) in
augmentation of skin flap blood flow and viability in the pig.
Prostaglandins. 1991;41:537–558.
177. Zhong A, Pang CY, Sheffield WD, et al. Augmentation of acute
random pattern skin flap viability in the pig. J Surg Res.
1992;52:177–183.
178. Kryger Z, Zhang F, Dogan T, et al. The effects of VEGF on survival
of a random flap in the rat: examination of various routes of
administration. Br J Plast Surg. 2000;53:234–239.
179. Zhang F, Oswald T, Lin S, et al. Vascular endothelial growth factor
(VEGF) expression and the effect of exogenous VEGF on survival
of a random flap in the rat. Br J Plast Surg. 2003;56:653–659.
180. Padubidri A, Browne E Jr. Effect of vascular endothelial growth
factor (VEGF) on survival of random extension of axial pattern
skin flaps in the rat. Ann Plast Surg. 1996;37:604–611.
181. Komorowska-Timek E, Timek TA, Brevetti LS, et al. The effect of
single administration of vascular endothelial growth factor or
L-arginine on necrosis and vasculature of the epigastric flap in the
rat model. Br J Plast Surg. 2004;57:317–325.
182. Seify H, Bulky U, Jones G. Effect of vascular endothelial growth
factor-induced angiogenesis on TRAM flap harvesting after
abdominoplasty. Plast Reconstr Surg. 2003;111:1212–1216.
183. Im MJ, Kim YS, Edwards RJ, et al. The effect of bovine basic
fibroblast growth factor on skin flap survival in rats. Ann Plast
Surg. 1992;28:242–245.
184. Ishiguro N, Yabe Y, Shimizu T, et al. Basic fibroblast growth factor
has a beneficial effect on the viability of random skin flaps in rats.
Ann Plast Surg. 1994;32:356–360.
185. Uhl E, Barker JH, Bondar I, et al. Improvement of skin flap
perfusion by subdermal injection of recombinant human basic
fibroblast growth factor. Ann Plast Surg. 1994;32:361–365,
discussion 365–366.
186. Carroll CM, Carroll SM, Schuschke DA, et al. Augmentation of
skeletal muscle flap survival using platelet derived growth factor.
Plast Reconstr Surg. 1998;102:407–415.
187. Khan A, Ashrafpour H, Huang N, et al. Acute local subcutaneous
VEGF165 injection for augmentation of skin flap viability: efficacy
and mechanism. Am J Physiol Regul Integr Comp Physiol.
2004;287:R1219–R1229.
188. Ashrafpour H, Huang N, Neligan PC, et al. Vasodilator effect
and mechanism of action of vascular endothelial growth factor
in skin vasculature. Am J Physiol Heart Circ Physiol. 2004;286:
H946–H954.
189. Shima DT, Deutsch U, D’Amore PA. Hypoxic induction of vascular
endothelial growth factor (VEGF) in human epithelial cells is
mediated by increases in mRNA stability. FEBS Lett.
1995;370:203–208.
190. Waller W, Lee J, Zhang F, et al. Gene therapy in flap survival.
Microsurgery. 2004;24:168–173.
191. Gurunluoglu R, Ozer K, Skugor B, et al. Effect of transfection time
on the survival of epigastric skin flaps pretreated with adenovirus
encoding the VEGF gene. Ann Plast Surg. 2002;49:161–169.
192. Lubiatowski P, Goldman CK, Gurunluoglu R, et al. Enhancement
of epigastric skin flap survival by adenovirus-mediated VEGF
gene therapy. Plast Reconstr Surg. 2002;109:1986–1993.
193. Liu PY, Tong W, Liu K, et al. Liposome-mediated transfer of
vascular endothelial growth factor cDNA augments survival of
random-pattern skin flaps in the rat. Wound Repair Regen.
2004;12:80–85.
194. Giunta RE, Holzbach T, Taskov C, et al. AdVEGF165 gene transfer
increases survival in overdimensioned skin flaps. J Gene Med.
2005;7:297–306.
195. Zhang F, Yang F, Hu EC, et al. Vascular endothelial growth factor
gene therapy in improvement of skin paddle survival in a rat
TRAM flap model. J Reconstr Microsurg. 2005;21:391–396.
196. Zacchigna S, Papa G, Antonini A, et al. Improved survival of
ischemic cutaneous and musculocutaneous flaps after vascular
endothelial growth factor gene transfer using adeno-associated
virus vectors. Am J Pathol. 2005;167:981–991.
197. Huang N, Khan A, Ashrafpour H, et al. Efficacy and mechanism
of adenovirus-mediated VEGF-165 gene therapy for augmentation
of skin flap viability. Am J Physiol Heart Circ Physiol.
2006;291:H127–H137.
198. Johnson PC, Barker JH. Thrombosis and antithrombotic therapy in
microvascular surgery. Clin Plast Surg. 1992;19:799–807.
199. Conrad MH, Adams WP Jr. Pharmacologic optimization of
microsurgery in the new millennium. Plast Reconstr Surg.
2001;108:2088–2096, quiz 2097.
200. Addison PD, Neligan PC, Pang CY. Drugs in Microsurgery.
In: Neligan PC, Wei FC, eds. Microsurgical Reconstruction of the
Head and Neck. St. Louis, MO: Quality Medical Publishing;
2010:159.
201. Greenberg BM, Masem M, May JW Jr. Therapeutic value of
intravenous heparin in microvascular surgery: an experimental
vascular thrombosis study. Plast Reconstr Surg. 1988;82:463–472.
202. Kroll SS, Miller MJ, Reece GP, et al. Anticoagulants and
hematomas in free flap surgery. Plast Reconstr Surg.
1995;96:643–647.
203. Chen CM, Ashjian P, Disa JJ, et al. Is the use of intraoperative
heparin safe? Plast Reconstr Surg. 2008;121:49e–53e.
204. Jackson MR, Clagett GP. Antithrombotic therapy in peripheral
arterial occlusive disease. Chest. 1998;114(suppl):666S–682S.
205. Moncada S, Korbut R. Dipyridamole and other phosphodiesterase
inhibitors act as antithrombotic agents by potentiating endogenous
prostacyclin. Lancet. 1978;1:1286–1289.
206. Peter FW, Franken RJ, Wang WZ, et al. Effect of low dose aspirin
on thrombus formation at arterial and venous microanastomoses
and on the tissue microcirculation. Plast Reconstr Surg.
1997;99:1112–1121.
207. Weksler BB, Pett SB, Alonso D, et al. Differential inhibition by
aspirin of vascular and platelet prostaglandin synthesis in
atherosclerotic patients. N Engl J Med. 1983;308:800–805.
208. Clarke RJ, Mayo G, Price P, et al. Suppression of thromboxane A2
but not of systemic prostacyclin by controlled-release aspirin. N
Engl J Med. 1991;325:1137–1141.
209. Bochner F, Lloyd J. Is there an optimal dose and formulation of
aspirin to prevent arterial thrombo-embolism in man? Clin Sci.
1986;71:625–631.
210. Patrignani P, Filabozzi P, Patrono C. Selective cumulative
inhibition of platelet thromboxane production by low-dose aspirin
in healthy subjects. J Clin Invest. 1982;69:1366–1372.
211. Chien W, Varvares MA, Hadlock T, et al. Effects of aspirin and
low-dose heparin in head and neck reconstruction using
microvascular free flaps. Laryngoscope. 2005;115:973–976.
212. Collaborative overview of randomised trials of antiplatelet
therapy–III: reduction in venous thrombosis and pulmonary
embolism by antiplatelet prophylaxis among surgical and medical
patients. Antiplatelet Trialists’ Collaboration. Br Med J.
1994;308:235–246.
213. Atik M. Dextran 40 and dextran 70. A review. Arch Surg.
1967;94:664–672.
214. Nearman HS, Herman ML. Toxic effects of colloids in the intensive
care unit. Crit Care Clin. 1991;7:713–723.
215. Disa JJ, Polvora VP, Pusic AL, et al. Dextran-related complications
in head and neck microsurgery: do the benefits outweigh the
risks? A prospective randomized analysis. Plast Reconstr Surg.
2003;112:1534–1539.
216. Sun TB, Chien SH, Lee JT, Cheng LF, et al. Is dextran infusion as
an antithrombotic agent necessary in microvascular reconstruction
of the upper aerodigestive tract? J Reconstr Microsurg.
2003;19:463–466.
217. Ridha H, Jallali N, Butler PE. The use of dextran post free tissue
transfer. J Plast Reconstr Aesthet Surg. 2006;59:951–954.
218. Panchapakesan V, Addison P, Beausang E, et al. Role of
thrombolysis in free-flap salvage. J Reconstr Microsurg.
2003;19:523–530.
219. Cange S, Laberge LC, Rivard GE, et al. Streptokinase in the
management of limb arterial thrombosis following free-flap
surgery. Plast Reconstr Surg. 1987;79:974–976.

443.e6
CHAPTER 23 • Flap pathophysiology and pharmacology
220. Lipton HA, Jupiter JB. Streptokinase salvage of a free-tissue
transfer: case report and review of the literature. Plast Reconstr
Surg. 1987;79:977–981.
221. Schubert W, Hunter DW, Guzman-Stein G, et al. Use of
streptokinase for the salvage of a free flap: case report and review
of the use of thrombolytic therapy. Microsurgery. 1987;8:117–121.
222. Goldberg JA, Pederson WC, Barwick WJ. Salvage of free tissue
transfers using thrombolytic agents. J Reconstr Microsurg.
1989;5:351–356.
223. Tonks AM, Rees M. Streptokinase salvage of a rectus abdominis
free flap. Plast Reconstr Surg. 1995;95:933–934.
224. Rooks MD, Rodriguez J Jr, Blechner M, et al. Comparative study of
intraarterial and intravenous anticoagulants in microvascular
anastomoses. Microsurgery. 1994;15:123–129.
225. Serletti JM, Moran SL, Orlando GS, et al. Urokinase protocol for
free-flap salvage following prolonged venous thrombosis. Plast
Reconstr Surg. 1998;102:1947–1953.
226. Yii NW, Evans GR, Miller MJ, et al. Thrombolytic therapy: what is
its role in free flap salvage? Ann Plast Surg. 2001;46:601–604.
227. Trussler AP, Watson JP, Crisera CA. Late free-flap salvage with
catheter-directed thrombolysis. Microsurgery. 2008;28:217–222.
228. Atiyeh BS, Fuleihan NS, Musharafieh RS. Pharmacologic partial
salvage of a failing free flap with recombinant tissue plasminogen
activator (rt-PA). J Reconstr Microsurg. 1999;15:585–590.
229. Parry DJ, Byrne P, Kessel D, et al. Pharmacological salvage of a
combined distal bypass and free flap with catheter-directed
thrombolysis. Br J Plast Surg. 2002;55:140–144.
230. Tran NV, Bishop AT, Convery PA, et al. Venous congestive flap
salvage with subcutaneous rtPA. Microsurgery. 2006;26:370–372.
231. Rinker BD, Stewart DH, Pu LL, et al. Role of recombinant tissue
plasminogen activator in free flap salvage. J Reconstr Microsurg.
2007;23:69–73.
232. Bevan JA. Antianginal and Vasodilator Drugs. In: Bevan JA, ed.
Essentials of Pharmacology. Hagerstown, MD: Harper & Row;
1976:276.
233. Benowitz NL. Antihypertensive Agents. In: Katzung BG, ed. Basic
and Clinical Pharmacology. New York: McGraw-Hill; 2004:159.
234. Puckett CL, Winters RR, Geter RK, et al. Studies of pathologic
vasoconstriction (vasospasm) in microvascular surgery. J Hand
Surg Am. 1985;10:343–349.
235. Granfeldt A, Lefer DJ, Vinten-Johansen J. Protective ischaemia in
patients: preconditioning and postconditioning. Cardiovasc Res.
2009;83:234–246.
236. Murry CE, Jennings RB, Reimer KA. Preconditioning with
ischemia: a delay of lethal cell injury in ischemic myocardium.
Circulation. 1986;74:1124–1136.
237. Mounsey RA, Pang CY, Boyd JB, et al. Augmentation of skeletal
muscle survival in the latissimus dorsi porcine model using acute
ischemic preconditioning. J Otolaryngol. 1992;21:315–320.
238. Mounsey RA, Pang CY, Forrest C. Preconditioning: a new
technique for improved muscle flap survival. Otolaryngol Head
Neck Surg. 1992;107:549–552.
239. Pang CY, Forrest CR. Acute pharmacologic preconditioning as a
new concept and alternative approach for prevention of skeletal
muscle ischemic necrosis. Biochem Pharmacol. 1995;49:1023–1034.
240. Pang CY, Yang RZ, Zhong A, et al. Acute ischaemic
preconditioning protects against skeletal muscle infarction in the
pig. Cardiovasc Res. 1995;29:782–788.
241. Schroeder CA Jr, Lee HT, Shah PM, et al. Preconditioning with
ischemia or adenosine protects skeletal muscle from ischemic
tissue reperfusion injury. J Surg Res. 1996;63:29–34.
242. Mattei A, Sutter PM, Marx A, et al. Preconditioning with short
cycles improves ischemic tolerance in rat fast- and slow-twitch
skeletal muscle. Eur Surg Res. 2000;32:297–304.
243. Zhang F, Oswald T, Holt J, et al. Regulation of inducible nitric
oxide synthase in ischemic preconditioning of muscle flap in a rat
model. Ann Plast Surg. 2004;52:609–613.
244. Zahir TM, Zahir KS, Syed SA, et al. Ischemic preconditioning of
musculocutaneous flaps: effects of ischemia cycle length and
number of cycles. Ann Plast Surg. 1998;40:430–435.
245. Zahir KS, Syed SA, Zink JR, et al. Ischemic preconditioning
improves the survival of skin and myocutaneous flaps in a rat
model. Plast Reconstr Surg. 1998;102:140–150, discussion 151–152.
246. Loke KE, Woodman OL. Effect of ischaemic preconditioning on
vascular dysfunction induced by ischaemia and reperfusion in rat
hindquarters. Cardiovasc Res. 1996;32:1081–1087.
247. Wang WZ, Anderson G, Maldonado C, et al. Attenuation of
vasospasm and capillary no-reflow by ischemic preconditioning in
skeletal muscle. Microsurgery. 1996;17:324–329.
248. Jerome SN, Akimitsu T, Gute DC, et al. Ischemic preconditioning
attenuates capillary no-reflow induced by prolonged ischemia and
reperfusion. Am J Physiol. 1995;268:H2063–H2067.
249. Forrest CR, Neligan P, Zhong A, et al. Acute adenosine treatment
is effective in augmentation of ischemic tolerance in muscle flaps
in the pig. Plast Reconstr Surg. 1997;99:172–182.
250. Pang CY, Neligan P, Zhong A, et al. Effector mechanism of
adenosine in acute ischemic preconditioning of skeletal muscle
against infarction. Am J Physiol. 1997;273:R887–R895.
251. Pang CY, Neligan P, Xu H, et al. Role of ATP-sensitive K+ channels
in ischemic preconditioning of skeletal muscle against infarction.
Am J Physiol. 1997;273:H44–H51.
252. Hopper RA, Forrest CR, Xu H, et al. Role and mechanism of PKC
in ischemic preconditioning of pig skeletal muscle against
infarction. Am J Physiol Regul Integr Comp Physiol.
2000;279:R666–R676.
253. Pang CY, Forrest CR. Pharmacological preconditioning of skeletal
muscle against infarction. In: Preedy V, Peters T, eds. Skeletal
Muscle: Pathophysiology, Diagnosis and Management of Disease.
London: Greenwich Medical Media; 2002:623.
254. Addison P, Neligan P, Forrest C, et al. Acute adenosine treatment
is effective in augmentation of ischemic tolerance in muscle flaps
in the pig: an update. Plast Reconstr Surg. 2003;111:842–845.
255. Oxman T, Arad M, Klein R, et al. Limb ischemia preconditions the
heart against reperfusion tachyarrhythmia. Am J Physiol.
1997;273:H1707–H1712.
256. Addison PD, Neligan PC, Ashrafpour H, et al. Noninvasive
remote ischemic preconditioning for global protection of skeletal
muscle against infarction. Am J Physiol Heart Circ Physiol.
2003;285:H1435–H1443. This animal study demonstrates that
tourniquet-based ischemic preconditioning protects against distal muscle
against infarction. Direct antagonism was employed to implicate opioid
receptor activation as a mechanism for this phenomenon.
257. Moses MA, Addison PD, Neligan PC, et al. Mitochondrial KATP
channels in hindlimb remote ischemic preconditioning of skeletal
muscle against infarction. Am J Physiol Heart Circ Physiol.
2005;288:H559–H567.
258. Moses MA, Addison PD, Neligan PC, et al. Inducing late phase of
infarct protection in skeletal muscle by remote preconditioning:
efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol.
2005;289:R1609–R1617.
259. Baxter GF, Goma FM, Yellon DM. Characterisation of the infarct-
limiting effect of delayed preconditioning: timecourse and
dose-dependency studies in rabbit myocardium. Basic Res Cardiol.
1997;92:159–167.
260. Burckhartt B, Yang XM, Tsuchida A, et al. Acadesine extends the
window of protection afforded by ischaemic preconditioning in
conscious rabbits. Cardiovasc Res. 1995;29:653–657.
261. Yang XM, Baxter GF, Heads RJ, et al. Infarct limitation of the
second window of protection in a conscious rabbit model.
Cardiovasc Res. 1996;31:777–783.
262. Kuzuya T, Hoshida S, Yamashita N, et al. Delayed effects of
sublethal ischemia on the acquisition of tolerance to ischemia. Circ
Res. 1993;72:1293–1299.
263. Quan EE, Ramirez S, Tecimer T, et al. Late-phase ischemic
preconditioning in skeletal muscle: is the phenomenon protective?
Microsurgery. 2004;24:151–156.
264. Harralson T, Grossi FV, Quan EE, et al. Ischemic preconditioning
of skeletal muscle: duration of late-phase protection. Ann Plast
Surg. 2005;55:216–222.
265. Cahoon NJ, Naparus A, Ashrafpour H, et al. Pharmacologica
prophylactic treatment for perioperative protection of skeletal

443.e7
References
muscle from ischemia – reperfusion injury in reconstructive
surgery. Plast Reconstr Surg. 2013;131:473–485.
266. Khiabani KT, Kerrigan CL. The effects of the nitric oxide donor
SIN-1 on ischemia-reperfused cutaneous and myocutaneous flaps.
Plast Reconstr Surg. 2002;110:169–176.
267. McAllister SE, Ashrafpour H, Cahoon N, et al. Postconditioning
for salvage of ischemic skeletal muscle from reperfusion injury:
efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol.
2008;295:R681–R689.
268. Zhao ZQ, Corvera JS, Halkos ME, et al. Inhibition of myocardial
injury by ischemic postconditioning during reperfusion:
comparison with ischemic preconditioning. Am J Physiol Heart Circ
Physiol. 2003;285:H579–H588.
269. Park JW, Kang JW, Jeon WJ, et al. Postconditioning protects
skeletal muscle from ischemia–reperfusion injury. Microsurgery.
2010;30:223–229.
270. Mowlavi A, Ghavami A, Song YH, et al. Limited use of
cyclosporin A in skeletal muscle ischemia–reperfusion injury. Ann
Plast Surg. 2001;46:426–430.
271. Cahoon NJ, McAllister SE, Ashrafpour H, et al. Postischemic
conditioning of ischemic human skeletal muscle against
reperfusion injury: the role of the mitochondrial permeability
transitional pore (mPTP). Can J Plast Surg. 2009;17:53.
272. Naparus A, Ashrafpour H, Hofer SOP, et al. Efficacy and
mechanism of hypoxic post conditioning in salvage of ex vivo
human rectus abdominis muscle form hypoxia/reoxygenation
injury. Eur J Pharmacol. 2012;686:90–96.
273. McAllister SE, Moses MA, Jindal K, et al. Na+/H+ exchange
inhibitor cariporide attenuates skeletal muscle infarction when
administered before ischemia or reperfusion. J Appl Physiol.
2009;106:20–28.
274. Tressel SL, Kim H, Ni CW, et al. Angiopoietin-2 stimulates blood
flow recovery after femoral artery occlusion by inducing
inflammation and arteriogenesis. Arterioscler Thromb Vasc Biol.
2008;28:1989–1995.
275. Naparus A, Ashrafpour H, Huang N, et al. Combination of
hypoxic preconditioning and post conditioning does not induce
additive protection of ex vivo human skeletal muscle from
hypoxia/reoxygenation injury. J Cardiovasc Pharmacol.
2012;60:347–356.

24 
Principles and techniques of
microvascular surgery
Fu-Chan Wei, Nidal F. Al Deek, and Sherilyn Keng Lin Tay
SYNOPSIS
■ Microvascular surgery refers to the surgical coaptation of small
vessels usually around 1 mm in diameter under microscope
magnification. Microsurgery is a broader term not only limited to blood
vessels but also refers to coaptation of tiny nerves and lymphatics.
■ This technique has evolved significantly over the last four decades,
starting from revascularization and replantation in 1960 to free-flap
surgery.
■ The development of the operating microscope, microinstruments, and
ultra fine sutures have greatly aided its widespread use.
■ Despite various techniques having been developed for the handling of
small vessels, the most commonly used techniques are still the
end-to-end and end-to-side anastomosis and coupling devices.
Difficult situations such as vessel diameter discrepancy, inadequate
vessel length, and poor vessel quality can usually be overcome with
special techniques.
■ Advances in microsurgery leading to consistently high success rates
have made free tissue transfer a cost-effective, first-line option in
modern reconstructive surgery with superior results and high patient
satisfaction compared with conventional methods. Microsurgery,
however, is mentally and physically demanding. The need for special
training cannot be overemphasized.
■ Thorough preoperative planning, flexibility of the surgical plan, and
flawless execution are mandatory for successful free flap surgery.
■ Clinical assessment remains the gold standard in free flap monitoring.
Early detection of a failing free flap with prompt intervention greatly
improves the salvage rates. Pharmacological agents such as
low-dose heparin, PGE1 and dextran are also useful. Complications
of free tissue transfer are not only due to vascular compromise;
inadequate planning, inappropriate flap selection and/or flawed
execution can compromise the flap and/or the functional and aesthetic
outcomes.
■ Refined microsurgical techniques and improved postoperative care
such as specialized microsurgical intensive care units have led to a
96–98% success rate in developed centers nowadays. If the first
microsurgical reconstruction fails, a second microsurgical
reconstruction can still be attempted with good results after identifying
and managing potential causes.
■ Microsurgery will not decline but will continue to evolve. Microsurgery
has indeed revolutionized our approach to reconstructive challenges,
and with further refinements, we will see an even wider application;
particularly, in the fields of supermicrosurgery, free-style free flaps,
and composite tissue allotransplantation.
Introduction
Microsurgery is a general term for surgery requiring the
operating microscope. Depending on the structure operated
on and its size, terms such as microvascular surgery (surgery
on blood vessels around 1 mm), microneural surgery, micro­
lymphatic surgery, and microtubular surgery, etc., can be
coined.
Supramicrosurgery is an extreme microsurgery and refers
to anastomoses of vessels around 0.5 mm in diameter
(0.3–0.8 mm), invaluable in lymphatic reconstruction and
perforator-to-perforator anastomosis.1,2
Reconstructive microsurgery utilizes microsurgical and
supramicrosurgical techniques in procedures such as revascu­
larization, replantation, and auto- or allotransplantation to
solve problems arising from traumatic injuries, congenital
deformities, and tumor ablation. However, some of these
procedures are performed under loupe magnification (×2.5–8),
including vessel coaptation, especially when the diameter is
not too small (usually around 3 mm).
It is worth noting that microsurgical techniques and, to a
lesser degree, supramicrosurgery are not limited to plastic
surgery; however, the scope of practice within plastic surgery
remains the most diverse in modern surgery.
The era of microsurgery began with the invention of the
microscope in 1920. But the improvement in magnification
and illumination and the development of microinstruments
and ultrafine sutures are the leading factors for the widespread
use of the techniques.
Our approach to micro- and supramicrosurgery has
changed over time. Consistently reported high success
  Access video lecture content for this chapter online at expertconsult.com

445
Tools
40× magnifications can be provided by some microscopes
with instant magnification change, a variable working dis­
tance, and precise XY positioning.
Some microscopes such as Leica and OPMI Pentero incor­
porate intraoperative fluorescence tools to assist the surgeon,
which is an invaluable technique to check perfusion before
and after, in lymphatic microsurgical reconstruction, and
precise tumor ablation in neurosurgery.
The modern operating microscope can be mounted on a
stand, placed on a table top, or worn on the surgeon’s head.
Some of them can be hung on the ceiling or wall to conserve
floor space in the surgical suite. Microscopes that can be
moved from one room into another and used by different
surgical specialties are very desired and cost-effective;
however, ophthalmic surgical microscopes could be an excep­
tion due to the specialized lighting, focusing, and magnifica­
tion requirements.
When using the microscope, choosing the appropriate level
of magnification is important in order to maneuver the instru­
ments and perform the anastomosis efficiently. Low magnifi­
cation (6×–12×) can be used for vessel preparation and suture
tying while middle magnification (19×–15×) can be used for
suture placement. High magnification is usually only required
for very small vessel anastomosis and inspection of the anas­
tomosis. For tips for use, see Box 24.1.
Loupes
Loupes can provide magnifications of 2.5×–8× and may be
mounted on glasses or headbands. They are cost-effective,
portable, and offer operator freedom.30 Enhanced visualiza­
tion provided by loupes is invaluable for precise dissection of
tissues and placement of instruments and sutures. In experi­
enced hands, high-magnification loupes can even provide an
effective alternative to the operating microscope for vessels as
small as 1 mm. A retrospective study of 200 consecutive free
microvascular tissue transplantations compared the perfor­
mance of free tissue transplants with 3.5× loupes and the
operating microscope.24 There was no difference in outcome
between the two groups, with free-flap success rates of 99%
for both the loupe and the microscope groups. However,
microscopes were required when performing anastomoses in
children and on vessels of 1.5 mm or less in diameter. Despite
these studies, most centers still use the microscope for
its greater range of magnification and light sources. This
is particularly important for smaller-vessel anastomoses in
the era of perforator flap, free-style, and supramicrosurgery
practice.
rates of 97–100%, cost-effectiveness, superior functional,
aesthetic, and psychological outcomes compared with other
techniques have changed the indication for microsurgery
from being the last resort after failure of other options into
the first choice and reversed, as a result, the reconstructive
ladder.
However, and not being confused as a “double-edged
sword”, microsurgery comes with a high price, demanding
experience and resources. But with professional training,
specialized infrastructures, dedication, and support, micro­
surgery can be performed daily with convenience.
The focus of this chapter is the principles and techniques
of basic and advanced microsurgery and free tissue trans­
fer, including perforator free flaps, free-style free flaps,
allotransplantation, and possible future directions. Revascu­
larization and replantation are specifically covered in other
chapters.
Access the Historical Perspective section online at

Tools
Since the introduction of the triangulation technique for vessel
repair by Alexis Carrel, the diameter of vessels that can be
anastomosed has become progressively smaller, due largely
to developments in surgical techniques, surgical instrumenta­
tion and microsutures, and improved optics in present-day
microscopes.
Magnification under adequate illumination allows more
accurate perception of operative anatomy and positioning
of instrumentation, with improved outcomes and facilita­
tion of procedures that would be impossible to undertake
without assisted vision. Intraoperative magnification also
reduces surgeons’ fatigue as a result of improved ergo­
nomics. Two types of optical system are used by surgeons
to produce magnification – the surgical microscope and
loupes.
Surgical microscopes
The basic sophistication of today’s operating microscope
includes binocular head with adjustable eyepieces and a
teaching head to allow two people to work with magnification
in the operating field; there could be a third head for digital
recording. The heads should independently pivot and have
separate magnification levels with the flexibility to be retrofit­
ted with a camera to document the procedure on an SD card
or DVD as well as to allow colleagues to view the operation
in real time.
Tilt, focus, and zoom can be controlled via a foot pedal or
a hand control panel; the first keeps the surgeon’s hands free
to perform the surgery without interruption, but necessitates
coordination; the second option could be more practical as it
keeps all functions in one accessible place.
Antimicrobial-coated surfaces and internally routed cables
are very important because the controls, lighting, and docu­
mentation technology nowadays require wiring; loose wiring
can get in the way of the surgical team and can harbor
bacteria.
BOX 24.1  Tips for using surgical microscopes
• Familiarize yourself with the microscope
• Spend time getting the position right, making sure that the
interpupillary distance and diopter correction are right
• Use an adjustable seat if you intend to sit
• Sit comfortably with feet flat on the ground to provide a stable
base
• Upper extremities should be well supported, resting on folded
drapes as necessary, to minimize fatigue and tremor
• Focus should be adjusted with the scope at highest
magnification before starting

445.e1
Historical perspective
Historical perspective
The concept of vascular repair was first proposed by Paré in
1552. However, it was two centuries later before the first suc­
cessful brachial artery repair was performed in 17593 and even
later in 1897 when Murphy reported his successful end-to-end
anastomosis of the femoral artery by invagination of vessels
with fine silk.4 Building on Murphy’s work, Alexis Carrel
reported a technical breakthrough for performing end-to-end
vascular anastomoses using the triangulation method in
1902.5 This work was further expanded in collaboration with
Guthrie, and for his contributions in “vascular suture and the
transplantation of blood vessels and organs”, Alexis Carrel
was awarded the Nobel Prize in 1912.
Experimental limb replantation in dogs and other models
continued in microvascular surgery. However, it was the
isolation of heparin from the liver by a medical student,
McLean,6 and its clinical introduction as an anticoagulant to
control clotting two decades later7 as well as the use of the
operating microscope that gave microvascular surgery a giant
leap forward.
The compound microscope was invented by Janssen in
1590 and subsequently mass-produced by Carl Zeiss for labo­
ratory research in the late 1800s. However, it was not until
1921 that Carl-Olof Siggesson Nylen, a Swedish otologist, first
used a modified monocular Brinell–Leitz microscope for
animal surgery and then, later in November of the same year,
in a patient with chronic otitis and pseudofistula symptoms.8
Nylen’s microscope was soon replaced by a binocular micro­
scope, developed in 1922 by his colleague Gunnar Holmgren.
In 1946, Perritt applied the use of the microscope to
ophthalmology.
The stage for modern microvascular surgery was set in
1960 when vascular surgeons Jacobson and Suarez9,10 intro­
duced the diploscope, a stereoscopic microscope for simulta­
neous use by two surgeons, for anastomoses of vessels as
small as 1 mm in diameter. From this point onwards, the
microscope found extensive use in the fields of peripheral
nerve surgery,11,12 plastic and reconstructive surgery,13 experi­
mental transplantation,14 and neurosurgery.
The first clinical application of microvascular surgery was
in replantation. Malt and McKhann first reported the success­
ful replantation of several arms in 196415 whilst the first
complete thumb replantation was performed in 1965 by
Konatsu and Tamai with the aid of a microscope.3 Young
reported on their series of second toe-to-hand transfers in
196616 and a year later, Cobbett performed the first successful
great toe-to-thumb transfer in a human being.17
The first experimental flaps based on the superficial epigas­
tric vessels were transplanted in dogs and reported by Krizek
et al. in 1965.18 Antia performed the first clinical free flap, but
this was only reported several years later, in 1971.19 This
dermolipomatous groin flap for facial defect reconstruction
was, however, complicated by infection and at least partial
necrosis occurred. In 1970, the omental free flap by McLean
and Buncke was the first fully successful free flap20 and in
1973, Daniel and Taylor reported transfer of the first groin
flap.21
New flaps, mainly musculocutaneous, were designed next
and the indications for their use were expanded over the next
few decades. Complication and failure rates declined22,23 and
success rates today range between 95.9 and 99%,24,25 compared
to 74–91%22 in earlier times.
During the late 1980s and into the 1990s, research focused
on anatomy, flap physiology, better donor sites, and improved
survival. But it was not until the late 1980s that cutaneous
flaps based on perforator vessels finally evolved from conven­
tional musculocutaneous flaps, and intramuscular dissection
was born with preservation of function and major vessels. The
first true perforator flap was the deep inferior epigastric artery
perforator flap first reported in 1989 by Koshima and Soeda.26
The next milestone in free flap surgery was the free-style flap
that allowed the harvest of a paddle of skin based on an
audible perforator detected by a hand-held Doppler in an area
that had not been previously adequately studied, alleviating
concerns regarding vascular anomaly and leaving the door
open for up to 400 perforator flaps.
Reconstructive microsurgery witnessed another great
achievement when allotransplantation became a reality after
the first successful hand transplantation in 1998 in Lyon,
France, and in January of 1999 in Louisville, USA.27,28 The
international experience has reached 107 transplanted hand/
upper extremities in 72 patients by the year 2014.28
The first partial face transplantation was performed in 2005
in Lyon, France, too. However, the first total face transplanta­
tion was performed in 2010 in Barcelona, Spain. So far, 29
partial, near-total, and total face transplantations have been
performed.29
It is worth saying, though, that the widespread application
of allotransplantation will not depend on advances in micro­
surgery as much as immunosuppression!

446
CHAPTER 24 • Principles and techniques of microvascular surgery
Essential features in all microsurgical instruments include
fine tips to spread, hold, or cut delicate tissue and suture, a
nonreflective surface and comfortable handles that close
easily to prevent fatigue.32 Many of the instruments used in
microvascular surgery will also be spring-loaded, and choos­
ing the right spring tension is important – too weak and the
tips will close all the way just by holding the instrument; too
firm and your hand will fatigue after a short period of use.
Most microinstruments are made of heat-hardened stain­
less steel, which is more resistant to wear and tear. They are
prone to magnetization and should be stored on demagne­
tized or nonmagnetic shelves. If an instrument becomes
magnetized, placing it in a coil demagnetizer attached to a
regular alternating current supply and withdrawing it slowly
will help. Antimagnetic materials such as titanium are becom­
ing popular, promising to be rust-free and lighter in weight.
In reality, however, they too can become magnetized. Most
microinstruments are available with a round or flat handle,
and range from 10–18 cm in length depending on surgeon
preference and depth of working field. In general, shorter
instruments are used when the anastomosis is closer to the
surface, for example, in hand surgery, while instruments
longer than 18 cm are used for procedures involving free
tissue transfer. Longer instruments may also be balanced such
that the balance point rests in the webspace. The slight coun­
terweight at the end of the instrument reduces fatigue and
allows better control and precision.
All instrument manufacturers give instructions for mainte­
nance, and it is extremely important to follow these instruc­
tions to ensure maximal performance of the microinstruments.
It is advisable to store the microinstruments in specially
designed instrument cases and to protect their fine tips with
silicone or rubber tubes. To be effective, they need to be fine-
tipped with the jaws meeting precisely. The user should
therefore minimize damaging them by not using them for
anything other than handling vessels and nerves. Blood and
contaminants should be regularly cleaned off by the scrub
nurse during the course of surgery and finally rinsed with
distilled or deionized water to avoid staining of the instru­
ments. High chloride concentrations should be avoided as
they lead to pitting and corrosion.
Types
Scissors
Microvascular scissors should be spring-loaded with sharp
but gently curved blades and slightly rounded tips. When
held closed, they can be used safely as a dissecting probe
without the danger of damaging the vessel. Those designed
for trimming the adventitia off the vessel end have straight
blades with sharp tips and are also good for stitch-cutting.
Needle holders
Spring-loaded microvascular needle holders are held like
pencils, resting on the first web. The handle is ideally rounded
to allow the instrument to be rolled between the index and
middle fingers and the thumb during the passing of the
needle. Flat handles are also available. The jaws should be
thin and gently curved with narrow shoulders to be able to
grasp the microsutures. Needle holders could be also straight
but the curved are usually finer at the tip and more suitable
for vessel dilation. Some needle holders come with a ratchet
Types
Two types of loupe are used in surgery: the compound (Gali­
lean) and prismatic loupe. In contrast to single-lens off-the-
shelf magnifying reading glasses, compound loupes have
significantly superior optics. These consist of two magnifying
lenses separated by air, achieving higher magnification,
greater depth of field, and better working distance. However,
image quality tends to become distorted at magnifications
above 2.5× and all such lenses create a “halo” effect at the
periphery of the visual field which may disturb the surgeon.
These drawbacks are counterbalanced by their relatively low
cost and light weight and they are widely used and available
from most manufacturers.31
Prismatic loupes provide higher optical quality because of
a Schmidt prism, which lengthens the path of light through a
series of mirror reflections inside the loupe. They can provide
improved magnification, wider fields of view, and longer
depths of field or working distance, but are 30–40% heavier,
more expensive than compound loupes, and more easily
damaged.31
Choosing loupes
While choice of magnification is largely dependent on the
surgeon’s preference, as a rough guide, a 2.5× magnification
is often sufficient for hand surgery and flap harvesting. If the
loupes are to be used for perforator dissection or anastomoses,
3.5–4.5× magnifications may be more suitable although 2.5×
is sufficient enough for perforator dissection. It is important
to note that both the field of view and depth of field decrease
with increasing magnification, while the weight of the loupes
increases. Loupes with a magnification higher than 4.5× tend
to be cumbersome and too heavy for daily use (especially if
they are prismatic), resulting in neck tension and increased
fatigue. In such instances, opting for the microscope might be
a better option.
Once the magnification has been chosen, other features
such as lens design, working angle, and distances need to be
considered. Some might choose to have the loupes mounted
on glasses or headbands, while others might prefer through-
the-lens (loupes mounted to the lenses of the frames) over the
flip-up or snap-fit type. The latter permits cheaper changing
of the magnification and the ability to change the lens pre­
scription more conveniently. Some manufacturers can also
supply headlights for use where additional lighting may
be required – particularly useful with the use of higher
magnifications.
Microsurgical instruments
Even with excellent optical systems, it would not have been
possible for microsurgical techniques to have evolved without
parallel refinements in microsurgical instruments and suture
materials. Many fine instruments have been available for
many years from jewelers but most have been developed
during research on vascular, lymphatic, and neural microsur­
gery. A confusing array of instruments and supplies for
microsurgery is now available, but with experience, most
microsurgery can be done with surprisingly few instruments
and most surgeons will become proficient with a reasonably
small set.