SPECIAL TOPIC

Vascular Delay Revisited

Shadi Ghali, M.R.C.S.
Peter E. M. Butler,
F.R.C.S.I., F.R.C.S.(Plast.)
Oren M. Tepper, M.D.
Geoffrey C. Gurtner, M.D.
London, United Kingdom; New York,
N.Y.; and Stanford, Calif.
Summary: The technique of vascular delay has been used by plastic surgeons
for nearly 500 years and has proven useful for reliably transferring tissue and
allowing for a greater volume of tissue to be reliably harvested. Delay procedures
are an essential plastic surgical tool for a variety of aesthetic and reconstructive
procedures. Despite the widespread use of vascular delay procedures, the mech-
anism by which this phenomenon occurs remains unclear. A number of groups
have exhaustively examined microvascular changes that occur during vascular
delay. Theories have been proposed ranging from the dilation of choke vessels
to changes in metabolism and new blood vessel formation. Inherent in these
theories is the concept that ischemia is able to act as the primary stimulus for
vascular changes. The purpose of this review is to revisit the theories proposed
to underlie the delay phenomenon in light of recent advances in vascular
biology. In particular, the participation of bone marrow– derived endothelial
progenitor cells in the delay phenomenon is explored. Greater understanding
of the role these cells play in new blood vessel formation will be of consid-
erable clinical benefit to high-risk patients in future applications of delay
procedures. (Plast. Reconstr. Surg. 119: 1735, 2007.)

V
ascular delay, also known as the delay phe-
nomenon, is the rendering of a tissue
ischemic to increase vascularity before
transfer. This improves flap survival, increases
the length-to-breadth ratio in random pattern
flaps, and allows for the reliable transfer of
greater volumes of tissue in axial pattern flaps.1–3
Various techniques involve the division of vessels
at an initial operation or beneath and around
the perimeter of the proposed flap to improve
circulation from the base. Despite the use of
delay procedures in clinical practice, the mech-
anism by which this phenomenon occurs re-
mains unclear. This article revisits the early de-
scriptions of vascular delay and suggests some
novel mechanisms based on recent advances in
vascular stem cell biology.
The technique of vascular delay has been used
by plastic surgeons for hundreds of years. The
From the Department of Plastic Surgery, Royal Free Hospital,
University of London; Laboratory of Microvascular Research and
Vascular Tissue Engineering, Institute of Reconstructive Plastic
Surgery, New York University Medical Center; and Division of
Plastic Surgery, Stanford University School of Medicine.
Received for publication August 26, 2005; accepted October
21, 2005.
Winner of the 2003 Research Council Peter J. Gingrass
Award and the 2004 Plastic Surgery Educational Founda-
tion Bernard G. Sarnat Award to O.M.T.
Copyright ©2007 by the American Society of Plastic Surgeons
DOI: 10.1097/01.prs.0000246384.14593.6e
Viano family, in the fifteenth century, improved
on the design of the single pedicle flap for rhi-
noplasty by undercutting and separating fore-
arm flaps with medicated linen to allow them to
mature for a month before transfer to the nose.3
This concept was later publicized by the cele-
brated Gaspar Tagliacozzi in the sixteenth cen-
tury using his upper arm flap,4 followed by more
detailed description of these principles by Ham-
ilton in the nineteenth century.5 Gillies also
demonstrated the importance of surgical delay
in 1920 in his description of tubed pedicle flaps.6
Despite centuries of clinical data demonstrating
the utility of surgical delay, the first experimental
investigation into delayed flaps was undertaken by
Milton in 1965. In a porcine model, he demon-
strated superior flap survival in an undermined
bipedicle delayed flap (delayed for 2 weeks) com-
pared with an undermined U-shaped unipedicle
delayed flap. The optimal time for tissue transfer
was determined to be 2 weeks after delay in this
study.7 This work was quickly followed by that of
Myers in 1967, who determined the optimum time
for tissue transfer to be 8 to 10 days in a rabbit
model of bipedicled skin flaps.3
MECHANISM
Over the latter half of the twentieth century,
numerous investigators undertook experimental
work to gain insight into the mechanisms under-
lying vascular delay. These studies have high-
lighted both humoral and cellular components of

www.PRSJournal.com 1735

Table 1. Summary of Experimental Studies on the Delay Phenomenon
Author
Milton, 19657
Myers and Cherry, 19673
Finseth and Cutting, 19789
Cutting et al., 198110
Hendel et al., 198311,12
Sasaki and Pang, 198413
Murphy et al., 198551
Haughey and Panje, 198514
Pang et al., 198615
Jonsson et al., 198820
Boyd et al., 199078
Callegari et al., 199221
Ozgentas et al., 199482
Arranz Lopez et al., 199583
Morris and Taylor, 199516
Restifo et al., 199779
Barker et al., 199795
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Plastic and Reconstructive Surgery • May 2007
Study
Year Journal Model
1965 Br. J. Plast. Surg. Porcine
1967 Plast. Reconstr. Surg. Rabbit
1978 Plast. Reconstr. Surg. Rat
1981 Br. J. Plast. Surg. Dog
1983 Plast. Reconstr. Surg. Rat
1984 Plast. Reconstr. Surg. Porcine
1985 Br. J. Plast. Surg. Rat
1985 Arch. Otolaryngol. Porcine
1986 Plast. Reconstr. Surg. Porcine
1988 Plast. Reconstr. Surg. Dog/rabbit Increased oxygen delivery demonstrated in delayed
1990 Plast. Reconstr. Surg. Porcine
1992 Plast. Reconstr. Surg. Dog
1994 Plast. Reconstr. Surg. Rat
1995 Br. J. Plast. Surg. Rabbit
1995 Plast. Reconstr. Surg. Rabbit
1997 Plast. Reconstr. Surg. Rat
1997 Plast. Reconstr. Surg. Mouse
Major Finding
Superior skin flap survival was demonstrated in an
undermined bipedicle delayed flap.
The beneficial effects of delayed bipedicle flaps was
shown to begin at 48 hr, reach a maximum at 8
days, and decline after 10 days.
Increased flap survival produced by “delay” involving
denervation alone (leaving the vascular supply
intact) or by devascularization alone (leaving the
nerve supply intact).
Initial decrease in venous outflow in the first 48 hr in
delayed skin flaps. After 48 hr, total blood flow
markedly increased.
Xenon washout technique used to measure blood
flow. Initial increase in vasospastic tone in acutely
raised skin flaps. Later, vasodilation occurring in
“delayed” flaps.
Skin flap viability and capillary blood flow similar in
delayed flaps and flaps constructed on skin pockets,
but significantly higher than those of acute random
pattern skin flaps.
Thromboxane plus PGF2 transiently increased in
acute skin flaps, with a blunted response in the
subsequent raising of delayed flaps. PGE2 also
increased in delayed flaps.
7 days of delay doubled the area of skin sustained on
an islanded musculocutaneous flap compared with
controls.
Radioactive microspheres used to demonstrate a
significant increase in capillary blood flow in
random pattern skin flaps within 2 days of delay.
This leveled off after day 3, remaining unchanged
between days 4 and 14. No evidence of an increase
in density of arteries, but an increase was seen in
the distal portion of delayed skin flaps.
mongrel skin flaps at day 14. Blood flow rerouted
parallel to incision lines and increased first by
vasodilation and then angiogenesis until day 14 in a
rabbit ear chamber model.
Increased viability of skin paddles in delayed flaps,
achieved by ligation of the superior epigastric
vessels 4, 7, 14, and 28 days before raising TRAM
flaps. Viability was accompanied by an increase in
skin/muscle capillary blood flow.
Dilation and hypertrophy occurred maximally in the
zone of choke vessels in delayed skin and muscle
flaps. Tissue expansion also demonstrated similar
changes.
Ligation of the superficial inferior epigastric and
deep superior epigastric vessels (dominant pedicle)
7 days before TRAM flap surgery resulted in
significant improvement in skin paddle survival.
Using immunohistochemistry, flaps delayed 3 or 7
days showed signs of angiogenesis from 2–7 days
after definitive flap elevation.
Maximal choke vessel dilation was demonstrated in
dorsal skin flaps in the first 48–72 hr.
Delay effect in TRAM flaps significant at 7 days and
maximal at 14 days. This effect was more pronounced
in larger compared with smaller flaps.
Significant increase in distal muscle necrosis with delay
procedures, demonstrated with videomicroscopy in
latissimus dorsi flaps.
Volume 119, Number 6 • Vascular Delay Revisited

Table 1. (Continued)
Author
Carroll et al., 199858
Zahir et al., 199848
Barker et al., 199923
Dhar and Taylor, 199917
Morris and Yang, 199984
Banbury et al., 199918
Carroll et al., 200057
Sano et al., 200280
Wong et al., 200455
Lineaweaver et al., 200456
Park et al., 200481
Ceradini et al., 200486
Tepper et al., 200577
PGF2, prostaglandin F2; PGE2, prostaglandin E2; TRAM, transverse rectus abdominis myocutaneous; PDGF, platelet-derived growth factor; bFGF,
basic fibroblast growth factor; VEGF, vascular endothelial growth factor; EPC, endothelial progenitor cell; HIF-1, hypoxia inducible factor-1
(a transcription factor mediating the cellular response to hypoxia, regulating the expression of over 60 genes that affect cell survival and
metabolism in adverse conditions); SDF-1, stromal derived factor-1 (a chemokine mediating homing of stem cells to bone marrow).
Study
Year Journal Model Major Finding
1998 Plast. Reconstr. Surg. Mouse Increased flap survival and capillary formation in
latissimus dorsi flaps augmented with PDGF
compared with bipedicled delay flaps.
1998 Ann. Plast. Surg. Rat Surgical delay and ischemic preconditioning
improved TRAM flap survival 1.4 and 1.3 times,
respectively, and 1.8 times in combination.
1999 Br. J. Plast. Surg. Mouse Decreased ear necrosis significant after 6 days of
delay with demonstrable vessel directional changes.
1999 Plast. Reconstr. Surg. Rat/dog Permanent and irreversible dilation of choke vessels,
demonstrated maximally 48–72 hr after flap
elevation.
1999 Plast. Reconstr. Surg. Rabbit Increased capillary blood flow and muscle viability
demonstrated in muscle flaps delayed for 7 days.
1999 Plast. Reconstr. Surg. Rat Cremaster muscle denervation caused increased red
blood cell velocity, arteriolar dilation, and increased
numbers of sticking leukocytes.
2000 Plast. Reconstr. Surg. Dog Administration of bFGF immediately following a delay
procedure significantly increased muscle perfusion
by 20% and fatigue resistance by 300%.
2002 Plast. Reconstr. Surg. Rat 14-day TRAM flap delay by division of the contralateral
superficial inferior epigastric artery or the ipsilateral/
bilateral deep cranial epigastric vessels resulted in
improved flap survival.
2004 Plast. Reconstr. Surg. Rat Surgical delay (7, 14, or 21 days) of TRAM flaps
improved flap viability and significantly elevated
bFGF levels at day 3 after flap elevation.
2004 Ann. Plast. Surg. Rat Surgical delay resulted in increased bFGF and
increased VEGF expression and increased skin
paddle survival.
2004 Plast. Reconstr. Surg. Mouse Systemic delivery of EPCs increased neovascularization
in a dorsal cranially based ischemic flap. EPCs were
recruited by day 3 and were significant by day 14.
2004 Nat. Med. Mouse Significant improvement in Doppler blood flow and
capillary density demonstrated in ischemic flaps at
day 14. This is shown to be mediated by hypoxic
gradients by means of HIF-1–induced expression of
SDF-1.
2005 Blood Mouse Bone marrow–derived EPCs are recruited to ischemic
tissue within 72 hr. By day 14, proliferative clusters
of cells coalesced into vascular cords, which became
functional vessels by day 21.

vascular delay. From this work it appears that the
effects of vascular delay can be divided chrono-
logically into early and late effects. Early benefits
have been postulated to be derived from an alter-
ation in the sympathetic tone secondary to tran-
section of sympathetic fibers on completion of a
surgical delay procedure, leading to the dilation
and reorientation of choke vessels within the flap.
These changes occur in parallel with early meta-
bolic changes, leading to an increase in ischemic
tolerance of the tissue. Later benefits were sug-
gested to result from further changes in tissue
metabolism and an increase in new blood vessel
density in the flap. The various landmark studies
that have contributed to our current understand-
ing of the delay phenomenon are highlighted in
Table 1.
EARLY EFFECTS OF DELAY
Alteration in Sympathetic Tone
In the immediate postelevation period, the
hyperadrenergic state is thought to be a significant
contributor to ischemia. This state results from
division of the sympathetic nerves, releasing nor-
adrenaline from nerve endings. The initial pos-

1737

televation hyperadrenergic state is thought to last
up to 30 hours, causing vasoconstriction predom-
inantly affecting the precapillary sphincters, caus-
ing relative ischemia.8 On subsequent elevation of
the flap, this hyperadrenergic state is ameliorated
as the severed nerves are depleted of norepineph-
rine, resulting in vasodilation. This is supported by
the work of Finseth and Cutting,9,10 who maintain
that delay results in vasodilation secondary to sym-
pathectomy and subsequent increased nutrient
blood flow. They evaluated flap delay experimen-
tally in a rat neurovascular island flap, by dividing
the artery, vein, and nerve. A combination of all
three resulted in the greatest flap survival in their
model and division of vein alone had the least
benefit. Numerous authors have reported similar
findings using various techniques, corroborating
these findings of vasodilation in the first 2 to 3 days
after flap elevation11–20 (Table 1).
Dilatation of Choke Vessels and Reorientation
of Vessels
Other factors involved in the early delay phe-
nomenon result in increased blood flow and are
independent of sympathectomy. Anatomical stud-
ies have demonstrated an increase in the number
and size of vessels and a change in their orienta-
tion, favoring vessels parallel to the long axis of the
flap. Taylor et al.21,22 demonstrated experimentally
that the maximal anatomical effect on the arterial
side, following surgical delay, is at the level of the
choke vessels that link adjacent vascular territo-
ries. Clinically, this is the area of the flap that is
most likely to undergo necrosis, with demarcation
at the zone of the choke vessels. Anatomically,
these vessels increase appreciably in size in re-
sponse to delay.
A sequential increase in size of the choke ves-
sels occurs during the delay period, with a rapid
increase in size between 48 and 72 hours,16 ac-
companied by demonstrable vessel directional
changes.23 Similar vascular changes have been
noted with tissue expansion, another form of sur-
gical manipulation leading to localized ischemia.
Tissue expansion is therefore thought by some to
represent a form of delay, with demonstrable ves-
sel hypertrophy.13,16,17,21,22
Early Changes in Tissue Metabolism
Ischemic and remote ischemic precondition-
ing techniques involving the preclamping of a
pedicle or a distant extremity, respectively, fol-
lowed by reperfusion of the tissue also increase the
ischemic tolerance of flaps and can therefore be
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Plastic and Reconstructive Surgery • May 2007
thought of as a form of delay. Ischemic precon-
ditioning was originally described in the canine
heart by Murray et al. in 1986,24 who demonstrated
a 70 percent reduction of infarcted myocardium
in preconditioned dogs by subjecting the myo-
cardium to four cumulative 5-minute ischemic
periods before a further 40 minutes of pro-
longed ischemic insult. Later experimental re-
ports in other organ systems such as the liver25,26
and the kidney27 followed and have been applied
clinically in cardiac,28,29 hepatic resectional,30,31
and pulmonary surgery.32,33 Ischemic precondi-
tioning induces a biphasic protection against
ischemia/reperfusion injury following the initial
preconditioning event: an initial strong protective
stimulus that lasts 2 to 3 hours followed by a less
powerful prolonged stimulus lasting 48 to 96
hours.34
Preformed agonists such as adenosine, brady-
kinin, catecholamines, and opioids trigger the
early protective response through various cell
surface G-protein– coupled receptors,35 whereas
the delayed effect results in altered cell physi-
ology. Preconditioned tissues therefore exhibit
reduced energy requirements,36 altered energy
metabolism,37 better electrolyte homeostasis,38 less
reactive oxygen species,32 reduced release of acti-
vated neutrophils,39 reduced apoptosis,40 and bet-
ter microcirculatory perfusion,41 resulting in an
increase of the ischemic tolerance of tissues.
The benefits of ischemic preconditioning
have also been demonstrated experimentally by a
number of investigators in both free and pedicled
flaps42– 47 and have been shown to be additive to the
benefits of delay procedures.48 Although the ex-
perimental results appear promising, as with delay
procedures, few protocols have been translated
into clinical practice.49 Remote ischemic precon-
ditioning may be more clinically applicable in flap
surgery in the future, as this neither prolongs the
operation nor increases the frequency of the
procedure.47,50
LATE EFFECTS OF DELAY
Prolonged Changes in Tissue Metabolism
Delay also has late effects on tissue metabo-
lism, use of substrates (oxygen and glucose), and
balance of the products of arachidonic acid. Mur-
phy et al.51 showed in a rat skin flap model that
surgical delay produced an increase in the pro-
duction of arachidonic acid metabolites, with a
derangement of the normal equilibrium between
the vasodilating metabolite prostaglandin E2 and
the vasoconstricting metabolite prostaglandin F2␣,
Volume 119, Number 6 • Vascular Delay Revisited
and a marked increase in the vasoconstrictive sub-
stance thromboxane. During the delay period of
14 days, there was a gradual decrease in tissue
levels toward normal. Subsequent elevation of the
delayed flap produced a blunted response in
thromboxane production, an increase in prosta-
glandin E2 levels, and increased flap survival.
Acute elevation of an undelayed flap produced
more marked elevation of all metabolites, with
prolonged elevation of the vasoconstrictive pros-
taglandin F2␣ and thromboxane, progressive
ischemia, and decreased flap survival.
Neovascularization
One factor that is always present during vas-
cular delay is ischemia, acting as the primary stim-
ulus for vascular changes. The effects of ischemia
on vascular growth has been well studied in a
number of conditions, such as myocardial
ischemia, limb ischemia, and tumors, and impor-
tant parallels can be drawn between the known
effects in these conditions and the proposed
mechanism underlying the delay phenomenon.
Indeed, the debate over the cause of the delay
phenomenon in many ways mirrors the debate
regarding the mechanisms of new blood vessel
formation or neovascularization in cardiac and
peripheral vascular disease.52–54
Traditional concepts of blood vessel growth
under ischemic conditions are currently being
modified as new mechanisms of blood vessel
growth in adults are being discovered. Neovascu-
larization is thought to occur by way of two discrete
Fig. 1. Mechanisms of neovascularization. Adult blood vessel growth may re-
sult from a combination of both angiogenesis (left) and vasculogenesis (right).
EPCs, endothelial progenitor cells.
mechanisms: angiogenesis and vasculogenesis.
Angiogenesis is the sprouting of microvessels from
a preexisting capillary network, whereas vasculo-
genesis refers to blood vessel formation from bone
marrow– derived endothelial progenitor cells that
form new vessels in situ (Fig. 1).
Angiogenic cytokines/growth factors such as
basic fibroblast growth factor (bFGF)55 and vascu-
lar endothelial growth factor (VEGF) are in-
creased following delay and lead to new blood
vessel growth.56 Carroll et al.57 demonstrated in-
creased muscle perfusion in a canine model
of latissimus dorsi muscle delay using bFGF
administration and increased latissimus dorsi
muscle survival in a mouse model following
PDGF administration.58 These factors initiate local
changes, including vasodilation and increased vas-
cular permeability, the activation of resident en-
dothelial cells, and degradation of basement
membrane. They also stimulate endothelial cell
migration and proliferation and the formation of
capillary sprouts, ultimately leading to new blood
vessel formation.59
However, the recent discovery of endothelial
progenitor cells has provided evidence that vas-
culogenesis also occurs in adult tissues.60 – 62 These
cells have been isolated from the peripheral blood
of humans and demonstrated to differentiate into
blood vessels in situ, a process known as “postnatal
vasculogenesis.”63– 66 The participation of endothe-
lial progenitor cells has been well documented in
a number of conditions requiring neovasculariza-
tion, including peripheral vascular disease,63 myo-
1739

cardial ischemia,67 stroke,68,69 wound healing,63,70
retinopathy,71 and tumor growth.63,72 This has led
to the examination of endothelial progenitor cell
transplantation in the treatment of ischemic con-
ditions both experimentally73–75 and in clinical tri-
als following acute myocardial infarction.76
This new paradigm of adult vasculogenesis is
also relevant to the delay phenomenon. Our
group recently studied this process in a delay/
vascular ischemia mouse flap model and demon-
strated bone marrow– derived endothelial progen-
itor cell recruitment to ischemic tissue within 72
hours.77 Recruitment was directly proportional to
the degree of tissue ischemia. Growth factors/
cytokines, such as VEGF, are released during
ischemia, resulting in the mobilization of endo-
thelial progenitor cells from the bone marrow.
At 7 days, there were persistently elevated levels
of VEGF that correlated with increased numbers
of bone marrow– derived endothelial progenitor
cells within ischemic tissues. By day 14 after flap
elevation, these endothelial progenitor cell clus-
ters coalesced into vascular cords, becoming func-
tional vessels by day 21. Considered together,
these data indicated that hypoxia altered the vas-
cular endothelium in ischemic tissue to trap en-
dothelial progenitor cells in regions where neo-
vascularization is needed. Adherent endothelial
Fig. 2. Schematic representation of the proposed mechanism by which endothelial progenitor cells contribute to neovas-
cularization within ischemic tissue. EPCs, endothelial progenitor cells.
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Plastic and Reconstructive Surgery • May 2007
progenitor cells egressed into tissues and, in re-
sponse to local tissue hypoxia, proliferated and
assembled into tubes, resulting in neovasculariza-
tion by way of vasculogenesis (Fig. 2).
Unlike previous explanations of choke vessel
enlargement and angiogenesis, which are believed
to occur as early as a few days postoperatively,
postnatal vasculogenesis appears to be a more de-
layed process. Although trace numbers of endo-
thelial progenitor cells were found in the flap
tissue at days 3 and 7 after surgery, the contribu-
tion was maximal at 2 weeks, with large-caliber
vessels observed. Currently, many physicians ad-
vocate delay as early as 1 week before tissue trans-
fer based on studies showing that angiogenesis
and choke vessel enlargement begin as early as 48
hours.3,15,16,63,82– 84 Our data support the early find-
ings of Milton7 and others15,20,51,78 – 81 in which 2
weeks would be the optimal timing of vascular
delay in the clinical setting.
This work also has implications for clinical
attempts to therapeutically augment the blood
supply to flaps in delay procedures. In animal
models of ischemia (ischemic limb and myocar-
dium), endothelial progenitor cell transplanta-
tion has been shown to significantly enhance neo-
vascularization when compared with controls.73–75
This stem cell approach to the creation of new
Volume 119, Number 6 • Vascular Delay Revisited
blood vessels has produced results comparable to
those achieved by the administration of proangio-
genic cytokines but offers important advantages by
supplying both substrate (i.e., cells) and cyto-
kines/growth factors important for blood vessel
regeneration.85 It is known that growth factor ad-
ministration is a useful adjuvant to vascular delay,
acting to increase tissue perfusion and resistance
to fatigue.57,58 Studies in our laboratory using en-
dothelial progenitor cells to augment skin neo-
vascularization in a mouse model have indeed
shown an acceleration in new blood formation
and flap survival.77,81,86
Clinical Applications
The use of pedicled tube flaps relying on the
delay phenomenon has decreased considerably
over the past 30 years as the use of microvascular
free flaps has increased. The delay technique,
however, continues to be a critical tool for the
success of a number of frequently used flaps, in-
cluding the median forehead, groin, and local
flaps in the hand such as the cross-finger and
thenar flaps. Delay also remains important in pro-
cedures frequently complicated by unpredictable
Table 2. Summary of Clinical and Human Anatomical Studies on the Delay Phenomenon
Authors Journal Study Type
Taylor et al., 199222 Plast. Reconstr. Surg. Musculocutaneous flaps Intraoperative arteriograms and venograms
(LD and TRAM)
Codner et al., 199588 Plast. Reconstr. Surg. TRAM flap
Restifo et al., 199789 Plast. Reconstr. Surg. TRAM flap
Ribuffo et al., 199790 Plast. Reconstr. Surg. TRAM flap
Restifo et al., 199891 Plast. Reconstr. Surg. TRAM flap
Scheufler et al., 200092 Plast. Reconstr. Surg. TRAM flap
Erdmann et al., 200287 Plast. Reconstr. Surg. TRAM flap
LD, latissimus dorsi; TRAM, transverse rectus abdominis musculocutaneous.
partial flap necrosis or fat tissue necrosis, such as
the pedicled transverse rectus abdominis muscu-
locutaneous (TRAM) flap49 and the deep inferior
epigastric perforator, muscle-sparing flaps in
breast reconstruction. One series of 76 high-risk
patients (i.e., obesity, cigarette smoking, radiation
therapy) undergoing unipedicled TRAM flap
breast reconstruction, delayed by ligation of both
deep inferior epigastric arteries and veins 14 days
before flap transfer, showed a partial flap necrosis
rate of only 6.6 percent.87
Further clinical studies of delay performed in
high-risk patients (i.e., obesity, cigarette smoking,
radiotherapy) as outpatient surgery, followed by
TRAM flap surgery, have also shown increased
diameter and flow of the superior epigastric artery
and decreased flap necrosis.88 –90 Surgeons have
attempted to simplify multistage delay procedures
by laparoscopic/endoscopic techniques91 or in-
terventional radiologic methods92 to achieve de-
lay, with varying levels of success. A summary of
clinical studies of vascular delay is provided in
Table 2.
Interestingly, delay procedures have not been
widely studied in free flaps, probably because of
the inherent complexity and the robust vascularity
Major Findings
demonstrated choke vessel dilation. Anatomically
unfavorable valved vein segments became
regurgitant with delayed flaps.
Vascular delay caused an overall increase in arterial
pressure, from 13.3 mm Hg (control) to 40.3 mm
Hg (delayed), with a decrease in venous
congestion in TRAM flaps.
15 high-risk patients (obesity, smoking, prior
radiation therapy) had outpatient ligation of deep
and superficial inferior epigastric vessels, 7 days
preoperatively. Doppler examination of superior
epigastric vessel showed significant diameter and
flow at operation.
Laser Doppler used to show superior epigastric
artery dilation and decrease in resistivity index of
the vessel.
Endoscopic/laparoscopic delay procedure
performed on 8 high-risk breast reconstruction
cases. Increased superior epigastric artery diameter
and blood flow determined by ultrasonographic
flow studies 7 to 14 days later.
40 patients presented after a delay procedure by
selective embolization of the deep inferior
epigastric arteries for superiorly pedicled TRAM
flaps.
Retrospective chart review of 76 consecutive cases
of unipedicled delay TRAM flaps for breast
reconstruction.
1741

of free tissue transfer. Delay techniques have been
indirectly applied, however, to increase the area of
tissue available on axial vessels for free tissue trans-
fer by using expanded free flaps. This is particu-
larly useful in children93 and burn patients,94
where there may be insufficient tissue available at
free flap donor sites and may facilitate primary
closure of donor sites.
Future Directions
Because of the pioneering work carried out by
earlier investigators into the alteration of sympa-
thetic tone and the vasodilation and reorientation
of choke vessels, and because of more recent ad-
vances in our understanding of vascular stem cell
biology, a greater understanding of the mecha-
nisms contributing to the delay phenomenon has
been achieved. It would appear that the initial
increase in flap blood flow in the first few days
following delay procedures is caused by dilatation
of vessels, most prominently around choke vessels.
In addition, ischemic preconditioning also plays a
role. Later, however, the relatively ischemic flap
promotes neovascularization by a combination of
angiogenesis and vasculogenesis. The relative con-
tribution of each of these overlapping processes
remains to be determined and will vary according
to age and comorbidities, and may well vary in the
same individual for different flaps.
CONCLUSIONS
It will be of great interest in the future to
determine whether a stem cell approach involving
enhanced mobilization or increased local recruit-
ment of these vascular stem cells using a variety of
techniques can augment vasculogenesis. This
concept of “therapeutic vasculogenesis” may
prove to be of benefit in high-risk patients with
impaired vasculogenesis and offer a novel ap-
proach to our future clinical applications of the
delay phenomenon.
Oren M. Tepper, M.D.
Institute of Reconstructive Plastic Surgery
560 First Avenue, TH-169
New York, N.Y. 10016
oren.tepper@med.nyu.edu
DISCLOSURE
None of the authors has a financial interest in any
of the products, devices, or drugs mentioned in this
article.
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Plastic and Reconstructive Surgery • May 2007
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