Vol. 89, Issue 6, 2268-2275, December 2000
Pharmacological characterization of vasomotor activity of
human musculocutaneous perforator artery and vein
Jianrong
Zhang1,
Joan E.
Lipa1,2,
Claire E.
Black1,2,
Ning
Huang1,
Peter C.
Neligan1,2,
Francis T. K.
Ling1,
Ronald H.
Levine2,
John L.
Semple2, and
Cho Y.
Pang1,2,3
1 Research Institute, Hospital for Sick Children, and
Departments of 2 Surgery and 3 Physiology, University
of Toronto, Toronto, Ontario, Canada M5G 1X8
 |
ABSTRACT |
Vasospasm is one
of the main causes of skin ischemic necrosis in cutaneous and
musculocutaneous flap surgery, but the pathogenic mechanism is
unclear. We planned to test the hypothesis derived from
clinical impression that veins are more susceptible to vasospasm than
arteries in flap surgery and, once established, that venous vasospasm
is difficult to resolve and more detrimental than arterial vasospasm.
To this end, we investigated the differences in sensitivity to
vasoconstrictors and vasodilators between the human musculocutaneous perforator (MCP) artery and vein by measuring the isometric tension of
arterial and venous rings suspended in organ chambers. Vascular contraction was expressed as a percentage of the tension induced by 50 mM KCl. Relaxation was expressed as a percentage of contraction induced
by a submaximal concentration (3 × 10
9 M) of
endothelin-1 (ET-1). We observed that the vasoconstrictor potency of
norepinephrine was significantly higher in the MCP vein than in the MCP
artery. The vasoconstrictor potency of ET-1 and the thromboxane
A2 mimetic U-46619 were similar in the MCP vein and artery,
but the maximal contraction induced by ET-1 and U-46619 was
significantly higher in the MCP vein than in the MCP artery. On the
other hand, the MCP vein was less sensitive than the MCP artery to the
relaxation effect of nitroglycerin, nifedipine, and lidocaine. These
differences between the human MCP artery and vein in response to
vasoactive agents lend support to the clinical impression in flap
surgery that veins appear to be more susceptible to vasospasm than
arteries and venous vasospasm seems to be more difficult to resolve
than arterial vasospasm in cutaneous and musculocutaneous flap surgery.
tissue transplant; free flap; microvascular surgery; vasospasm; ischemic necrosis
| |
INTRODUCTION |
SURGERY FOR THE
TREATMENT of trauma, congenital malformations, burns, and tumors
often produces large, deep wounds in which vital structures may be
exposed. Failure to close these wounds and achieve wound healing may
destroy the exposed tissues, such as nerves, blood vessels, tendons, or
bones, resulting in loss of form and/or function in that part of the
body. Autogenous skin or skin and muscle transplantation (i.e.,
cutaneous or musculocutaneous free flap surgery) is routinely used for
wound coverage. Specifically, a cutaneous or musculocutaneous flap is
harvested from a distant donor site of the body and is transferred to
cover the wound, with vascular anastomosis performed at the recipient
site to reestablish blood supply (8). Despite advances in
microsurgical technique, patient selection, judicious donor site
selection, and recipient site preparation, flap failure associated with
vasospasm and thrombosis still occurs at a rate of 5-10%, even in
large medical centers (3). Vasospasm can occur
intraoperatively and shortly after release of the vascular clamp after
vascular anastomosis, but vasospasm can also occur within 48-72 h
postoperatively. Vasospasm plays an important role in the pathogenesis
of thrombosis, causing partial or total flap ischemic necrosis
(33, 57). Flap failure is time consuming and costly
because it requires additional surgery and a prolonged period of
hospitalization. In the United States, the operating room costs range
from $44,000 to $68,000 for each total free flap failure (19,
52), and the additional surgeon reimbursements range from $5,000
to $35,000 (52). Furthermore, repeated reconstructive
surgery may increase donor site deformity and morbidity, which may have
a devastating effect on the patient. Therefore, there is the need to
understand the pathophysiology of vasospasm in free flap surgery to
develop an effective pharmacological intervention for prevention and/or
mitigation of vasospasm in flap surgery.
The mechanism for vasospasm in free flap surgery is unclear. It seems
that mechanical stretch or trauma may induce a myogenic response,
causing vasospasm. In addition, surgical trauma may induce local
vasospasm by stimulating the sympathetic nerve ending to release
norepinephrine (NE). The synthesis and release of endothelium-derived relaxing factors (EDRFs), such as prostacyclin (PGI2) and
nitric oxide (NO), may be reduced, or synthesis and release of
endothelium-derived contracting factors, such as thromboxane
A2 (TxA2) and endothelin-1 (ET-1), may be
augmented (4, 8, 41, 42). Last but not least, reduced
local blood flow due to vasospasm may also increase the thrombogenic
nature of the suture lines of the vascular anastomosis. This may in
turn promote platelet release of vasoconstrictive and prothrombotic
substances such as NE, TxA2, and serotonin
[5-hydroxytryptamine (5-HT)] (29). Venous congestion,
i.e., "blue flap," is a common pathology in skin flap failure and
is likely induced by venous spasm. There is the clinical impression
among surgeons that veins appear to be more susceptible to vasospasm
than arteries in flap surgery and, once established, venous spasm seems
to be more difficult to resolve than arterial vasospasm
(23). In addition, there is experimental evidence to
indicate that venous ischemia is more injurious in flap surgery
(26). These observations imply that venous vasospasm is an
important pathogenic mechanism in free flap surgery. This study was
designed to investigate whether indeed the human musculocutaneous
perforator (MCP) vein is more susceptible to vasospasm than the MCP
artery and whether this susceptibility is related to differences in
sensitivity to vasoactive agents. The MCP artery and vein were chosen
for this study because the MCP artery supplies blood to the muscle and
skin from the segmental artery and this pattern of blood supply is
relevant to musculocutaneous pedicled and free flap surgery.
| |
MATERIALS AND METHODS |
Source of human blood vessels.
The skin pannus excised from patients undergoing abdominoplasty serves
no purpose to the patient and is normally disposed of by incineration.
A clinical protocol was approved to obtain MCP arteries and veins from
the skin pannus after it was excised from the patient. Another protocol
was also approved to obtain MCP artery and vein specimens (~1.0 cm in
length) from patients undergoing transverse rectus abdominis
musculocutaneous flap surgery. Obtaining these vascular specimens did
not affect the procedure or outcome of the surgery. The blood vessel
specimens were wrapped in gauze soaked with isotonic saline. The
specimens were transported to the laboratory at room temperature. This
mimicked the clinical situation in which the free flap is subjected to
ischemia in room temperature during anastomosis at the recipient site.
The vascular specimens were used for experimentation within 45-60
min after excision. This ischemic period may be slightly shorter than
the ischemic time for free flap surgery in some cases. The subjects were female (40-60 yr of age) and were not known to smoke or have any systemic disease.
Preparation of vascular rings and tension recording.
The MCP artery and vein specimens were placed in oxygenated
Krebs-bicarbonate solution at room temperature, cleared of loose connective tissue, and cut into 4-mm-long rings. The outer diameter of
these vascular rings was 1-2 mm. Two stainless steel wires were
placed through the lumen of each ring. An arterial and a venous ring
were used in each experiment. Each ring was placed in an organ chamber
of 25-ml volume. One wire was anchored to the bottom of the organ
chamber, whereas the other was connected to a Grass FT 0.03 force
transducer (Grass Instrument, Quincy, MA) for the measurement of
isometric force. Isometric contractions were recorded on a Grass model
75 polygraph. The ring was equilibrated in the organ chamber in
Krebs-bicarbonate solution containing (in mM) 118.4 NaCl, 4.7 KCl, 2.25 CaCl2, 1.2 MgSO4, 1.2 KH2PO4, 25 NaHCO3, and 11 glucose.
The Krebs-bicarbonate solution was gassed with 95% oxygen-5% carbon
dioxide and maintained at 37°C and pH 7.4. Arterial and venous rings
were equilibrated under resting tensions of 2 and 0.5 g,
respectively, which were determined, in a preliminary experiment, to be
optimal for maximal tension development by 50 mM KCl. The endothelium
was intentionally preserved by cautiously mounting the vascular rings,
and the endothelium-dependent relaxation response of vascular rings to
acetylcholine was tested in each experiment.
Clinically, vasospasm in microvascular surgery is probably caused by a
myogenic response induced by mechanical stretch or trauma and local
release of vasoconstrictor substances. In the present studies, vascular
contraction was induced by exogenous vasoconstrictors, which are known
to be associated with experimental skin flap vasospasm.
Protocol 1.
Each arterial and venous ring was equilibrated in Krebs-bicarbonate
solution for ~30 min with continuous readjustment of resting tension
to 2 g for arterial and 0.5 g for venous rings. At the end of
the equilibration period, the absolute contract to 50 mM KCl was
obtained. After three washings with Krebs-bicarbonate solution, the
ring was allowed to stabilize for at least 30 min before an experiment
was started. Vascular contractions to various vasoconstricting agents
were expressed as a percent increase in tension induced by 50 mM KCl.
Cumulative concentration response curves for MCP arteries and veins
were obtained to the following agents: ET-1 (1010 to
5 × 108 M), the stable TxA2 mimetic
U-46619 (109 to 5 × 106 M), and NE
(108 to 5 × 105 M). Cumulative
concentration-response curves were constructed by step addition of
the constrictor substances to the organ chamber solution. Each
increment was made only after the response for the preceding
concentration of drug had stabilized (40 min for ET-1, 15 min for
U-44619 and NE). Each ring was used to obtain the
concentration-response curve for only one drug. At the end of each
experiment, the presence of functional endothelium in the vascular ring
was determined by testing the relaxation response to 105
M acetylcholine.
Protocol 2.
For relaxation experiments, each MCP artery and vein was preconstricted
with a submaximal dose of ET-1 (3 × 109 M).
Preliminary experiments indicated that the onset of contraction to ET-1
was slow and the maximal contraction was reached at ~30 min and
sustained for >140 min. Immediately after the maximum contraction was
achieved, the cumulative concentration-dependent relaxation effect of
nitroglycerin, papaverine, nifedipine, or lidocaine (Xylocaine) was
studied in arterial and venous rings. Cumulative concentration-response
curves were constructed by addition of the vasodilator drugs to the
organ chamber solution in 0.5-log unit steps. Each step was made only
after the relaxation response had stabilized (~15 min). Each arterial
and venous ring specimen was used to obtain the relaxation
concentration-response curve for one drug only.
Biochemicals.
Unless otherwise stated, all chemicals, except for the following, were
purchased from Sigma Chemical (St. Louis, MO): ET-1 from Peptide
International (Louisville, KY), U-46619 from Caymen (Ann Arbor, MI), NE
and nitroglycerin from SABEX (Boucherville, Quebec), and lidocaine from
Abbott Laboratory (St. Laurent, Quebec).
ET-1 was dissolved in 0.1% acetic acid and was stored at 
70°C for
no longer than 30 days before use. To make stock solutions, NE was
dissolved in 5 ml of 5% dextrose at the concentration of 6 × 103 M. Papaverine and nifedipine were dissolved in 0.5 ml
of DMSO at the concentration of 102 M. Injectable
lidocaine was dissolved in perfusion solution. Krebs-bicarbonate
solution and all drug stock solutions were made in the morning of each
experiment day and were kept at 4°C. Various concentrations of drugs
were made with 37°C Krebs-bicarbonate solution during the experiment.
The quantity of acetic acid, dextrose, and DMSO used for dissolving
drugs did not affect the isometric tension of the arterial and venous
rings tested (n = 3).
Data processing and statistical analysis.
Vascular contractions were expressed as a percentage of the tension
induced by 50 mM KCl. Vascular relaxations were expressed as a
percentage of contraction induced by 3 × 109 M
ET-1. The concentration of a drug exhibiting 50% of the maximal contraction or relaxation (EC50) was calculated for each
arterial or venous ring. Apparent affinity (pD2) was
calculated as negative log molar concentration of EC50.
All values are expressed are means ± SE. One-way analysis of
variance followed by Duncan's multiple-range test was used for comparison of mean values. Student's t-test was used for
comparison of two mean values. Statistical significance was set at
P < 0.05 for all tests. The number
(n) of observations indicates the number of blood vessels
obtained from different patients.
| |
RESULTS |
Contractions of the MCP artery and vein.
ET-1, U-46619, and NE elicited cumulative concentration-dependent
contraction in MCP arteries and veins (Figs.
1-3,
respectively). The order of vasoconstrictor potency in both MCP
arteries and veins as judged by the pD2 values was
ET-1 > U-46619 > NE (Table 1), and the differences were significant
(P < 0.05). The order of maximal contraction induced
by these vasoconstrictors was U-46619 > ET-1 = NE for MCP
arteries and U-46619 = ET-1 > NE for MCP veins (Table
2), and the differences were also
significant (P < 0.05).
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Fig. 1.
Cumulative concentration-dependent contractions to
endothelin-1 in the human musculocutaneous (MC) perforator artery and
vein with intact endothelium. Contractions are expressed as a
percentage of the tension induced by 50 mM KCl: 100% = 4.35 ± 0.11 g in MC perforator arteries and 1.57 ± 0.11 g in
MC perforator veins. [M], molar concentration. Values are means ± SE; n = 5 experiments.
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Table 1.
Vasoconstrictor potency of endothelin-1, U-46619, and
norepinephrine in the human musculocutaneous perforator artery and vein
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Table 2.
Maximal contraction effect of endothelin-1, U-46619, and norepinephrine
in the human musculocutaneous perforator artery and vein
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Comparison of contractions between the MCP artery and vein.
The vasoconstrictor potency of ET-1 and U-46619 as judged by
pD2 values (Table 1) was similar between the MCP artery and vein. However, the maximal contraction elicited by ET-1 was 56% higher
in the MCP vein compared with the MCP artery and for U-46619 was 38%
higher in the MCP vein than MCP artery (Figs. 1 and 2; Table 2). The
vasoconstrictor potency of NE was twofold higher (P < 0.05) in the MCP vein compared with the MCP artery (Table 1), but the
maximal contraction induced by NE was similar between the MCP artery
and vein (Table 2).
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Fig. 2.
Cumulative concentration-dependent contractions to
U-46619 in human MC perforator artery and vein with intact endothelium.
Contractions are expressed as a percentage of the tension induced by 50 mM KCl: 100% = 4.28 ± 0.10 g in MC perforator arteries and
1.54 ± 0.11 g in MC perforator veins. Values are means ± SE; n = 5 experiments.
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Relaxations of the MCP artery and vein.
Nitroglycerin, papaverine, nifedipine, and lidocaine elicited
concentration-dependent relaxation in MCP arteries and veins preconstricted with 3 × 109 M ET-1 (Fig.
4). The order of relaxation potency as
judged by the pD2 values was nitroglycerin > papaverine = nifedipine = lidocaine for MCP arteries and
nitroglycerin > papaverine > nifedipine = lidocaine
for MCP veins (Table 3), and the
differences were significant (P < 0.05). Next to
nitroglycerin, papaverine was the most effective vasodilator observed
in the present study. Specifically, the relaxation potency of
papaverine was similar between nifedipine and lidocaine in the MCP
artery but was significantly higher (P < 0.05) than nifedipine and lidocaine in the MCP vein (Table 3). The maximal relaxation effect was similar among nitroglycerin, papaverine, and
nifedipine in that they all completely mitigated ET-1-induced contraction in both MCP arteries and veins (Fig. 4). However, the
maximal relaxation achieved by lidocaine was only 48% in the MCP
artery and 49% in the MCP vein (Fig. 4).
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Fig. 3.
Cumulative concentration-dependent contractions to
norepinephrine in the human MC perforator artery and vein with intact
endothelium. Contractions are expressed as a percentage of the tension
induced by 50 mM KCl: 100% = 4.44 ± 0.10 g in MC perforator
arteries and 1.60 ± 0.11 g in MC perforator veins. Values
are means ± SE; n = 5 experiments.
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Fig. 4.
Cumulative concentration-dependent relaxations to
nitroglycerin, papaverine, nifedipine, and lidocaine in the human MC
perforator artery and vein with intact endothelium and preconstricted
with 3 × 109 M endothelin-1. Relaxations are
expressed as a percentage of the contraction induced by 3 × 109 M endothelin-1: 100% = 1.40 ± 0.05 g in
MC perforator arteries and 0.67 ± 0.02 g in MC perforator
veins. Values are means ± SE; n = 4 experiments
(nitroglycerin and papaverine) and n = 5 experiments
(nifedipine and lidocaine).
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Table 3.
Relaxation potency of nitroglycerin, papaverine, nifedipine, and
lidocaine in the human musculocutaneous perforator artery and vein
preconstricted with 3 × 109 M
endothelin-1
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Comparison of relaxation between the MCP artery and vein.
MCP veins preconstricted with ET-1 were less sensitive to the
relaxation effect of vasodilators than MCP arteries preconstricted with
the same concentration of ET-1. Specifically, the relaxation potency of
nitroglycerin, nifedipine, and lidocaine, as judged by their
pD2 values, was lower (P < 0.05) in the
MCP vein than in the MCP artery by 2.4-, 4.7-, and 5.8-fold,
respectively (Table 3). However, the relaxation potency of papaverine
was similar between the MCP artery and vein.
| |
DISCUSSION |
The present study demonstrated for the first time some differences
in the responsiveness of the human peripheral artery and vein to
vasoactive agents. Specifically, we observed that the vasoconstrictor
potency of NE was higher in the MCP vein than in the MCP artery.
Although the vasoconstrictor potency of ET-1 and U-46619 was similar
between the MCP artery and vein, their maximal contraction effect was
higher in the MCP vein than in the MCP artery. More importantly, MCP
veins preconstricted with a submaximal concentration of ET-1 were less
sensitive to the relaxation effect of nitroglycerin, nifedipine, and
lidocaine than MCP arteries preconstricted with the same concentration
of ET-1.
Explanation for differences in contraction between the human MCP
artery and vein.
In this study, we did not plan to investigate the mechanism responsible
for the differences in sensitivity to the vasoconstrictor effects of
NE, ET-1, and U-46619 between the human MCP artery and vein. These
vasoconstrictors were used because there is experimental evidence to
indicate that they most likely contribute to the pathogenesis of
vasospasm in flap surgery (4, 41-43). Other
investigators have observed that large canine veins were more sensitive
to the vasoconstrictor effect of ET-1 than were their paired arteries (7, 35) and the human internal mammary vein was more
sensitive to the vasoconstrictor effect of NE (31) and
ET-1 (6, 32, 59) than was its corresponding
artery. It was suggested that the greater vasoconstrictor effect of
ET-1 and NE in the human internal mammary vein than the artery may be
related to a greater vasoconstrictor effect of these vasoconstrictors
on venous smooth muscle cells, less release of EDRFs, or less
responsiveness to EDRFs in the vein than in the artery (31,
32). Further study is required to determine which of these
factors is responsible for the difference in responsiveness to
vasoconstrictors between the MCP artery and vein.
Relaxation mechanism.
Nitroglycerin, papaverine, nifedipine, and lidocaine are common
spasmolytic drugs (15-17, 51). Nitroglycerin releases
NO, which interacts with soluble guanylate cyclase to raise the
intracellular concentration of cGMP, which in turn mediates vascular
smooth muscle relaxation (44, 45). There is evidence to
indicate that cGMP may act to reduce intracellular Ca2+
concentration ([Ca2+]i) (1, 22)
and modulate the Ca2+ contractile apparatus in smooth
muscle cells (2, 25).
Papaverine is known to inhibit oxidative phosphorylation
(50) and increase intracellular accumulation of cAMP and
cGMP in vascular smooth muscle cells by inhibition of cAMP and cGMP
degradation by cyclic nucleotide phosphodiesterases (10, 28,
37). The accumulated cAMP and cGMP decrease
[Ca2+]i and the sensitivity of contractile
activity in vascular smooth muscle cells (5).
Nifedipine causes vasodilation by blocking entry of extracellular
Ca2+ from L-type Ca2+ channels
(20).
The mechanism of action of lidocaine is unclear. Its vasodilator effect
may be partly due to its inhibitory effect on local sympathetic nerves
and blocking of Na+ channels, thus leading to a decrease in
intracellular Na+ concentration, which in turn reduces
[Ca2+]i, resulting in vasodilation
(27).
Limitations of the present findings.
Experimental evidence presented thus far seems to indicate that
ET-1-preconstricted human MCP veins are less sensitive to vasodilators
such as nitroglycerin, nifedipine, and lidocaine than are MCP arteries.
However, further studies are required to demonstrate that these
differences between human MCP arteries and veins in their response to
the relaxation effect of these spasmolytic drugs are not limited to
ET-1-induced vasoconstriction. Specifically, Miller and Vanhoutte
(36) observed that the ability of NO donors to inhibit
contractions in canine femoral arteries and veins varied with the agent
used to activate the contraction. For example, it was reported that,
when ET-1 was used to contract the canine femoral arteries and veins,
3-morpholinosydnonimine was more potent in relaxing arteries than
veins, but this difference was not seen when these blood vessels were
contracted with NE. It has been demonstrated previously that 5-HT and
TxA2 (18, 40), but not NE (12),
are likely to be involved in the pathogenesis of vasospasm and
thrombosis in skin flap surgery. Therefore, future study with human MCP
arteries and veins is required to clarify the relaxation effect of
vasodilators on 5-HT- and TxA2-induced vascular contractions.
Clinical perspectives.
The effective agents for prevention and/or treatment of flap vasospasm
remain elusive. Results obtained from this study certainly indicate
that nitroglycerin is a potent vasodilator for resolving vasospasm in
both MCP arteries and veins intraoperatively. However, it is of
interest to investigate whether nitroglycerin can also be used as a
prophylactic agent for the prevention of perioperative vasospasm. More
importantly, it is well known that vasospasm and thrombosis can occur
within 24-48 h postoperatively, and the effectiveness of
nitroglycerin for prevention and/or treatment of postoperative vasospasm is unclear. Specifically, there are positive (9, 13,
43, 47, 51, 56) and negative (14, 39, 54) results
in the therapeutic effect of nitroglycerin in augmentation of skin flap
viability in laboratory animals. These controversial results may be
attributed to differences in flap models, dosage, and method of drug
administration. Nitroglycerin is a safe and inexpensive drug that can
be administered topically in cutaneous and musculocutaneous flaps.
Therefore, there is the need to elucidate the efficacy of nitroglycerin
for the prevention and/or treatment of intraoperative and postoperative
vasospasm in flap surgery.
The relaxation mechanism of nitroglycerin and an L-type
Ca2+ channel blocker are different; therefore, the combined
use of nitroglycerin and an L-type Ca2+ channel such as
nifedipine may potentially produce an additive effect against vasospasm
(15, 17). Theoretically, topical nitroglycerin in
combination with oral treatment of an L-type Ca2+ channel
blocker would provide optimal prevention and/or treatment against
intraoperative and postoperative vasospasm in flap surgery. However,
similarly to nitroglycerin, the experimental evidence concerning the
efficacy of L-type Ca2+ channel blockers for augmentation
of skin flap viability is equivocal at the present time (21, 24,
34, 38, 56). The dose-response effect of L-type Ca2+
channel blockers on skin hemodynamics and viability in flap surgery has
yet to be investigated. It has been demonstrated that the vasoconstrictor effect of ET-1 is mediated by ETA
receptors, with little participation from ETB receptors
(30). Therefore, selective ETA-receptor
antagonists may also be used as a combined treatment for skin flap
vasospasm. Papaverine is also a potent vasodilator in human MCP
arteries and veins. However, there is the suspicion that papaverine may
not be a drug of choice because commercially available papaverine
solution is highly acidic (pH 3.0-4.5) and can be potentially
damaging to endothelial cells. Papaverine is relatively unstable in
nonacidic solution (17, 49). In addition, papaverine is
not used systemically; thus the use of papaverine for the prevention
and/or treatment of postoperative vasospasm in flap surgery may be limited.
The effect of cyclooxygenase products on skin flap viability is
unclear. It was observed that intravenous infusion of prostacyclin (PGI2) did not increase skin flap distal perfusion or
viability in the pig (11). There were two clinical cases
in which aspirin and iloprost (a stable analog of PGI2)
were used as antithrombotic drugs for salvage of failing flaps
(46, 53), but the efficacy of these drugs for prevention
and/or treatment of skin flap thrombosis has yet to be documented
clinically. It is important to point out that there are potential
complications of postoperative bleeding and hematoma formation with the
use of antithrombotic agents in flap surgery.
In summary, using the vascular ring perfusion technique, we
demonstrated for the first time that the vasoconstrictor potency of NE
is higher in the human MCP vein than artery and the maximal contractions elicited by ET-1 and U-46619 are higher in the human MCP
vein than artery. On the other hand, the human MCP vein is less
sensitive to the relaxation effect of nitroglycerin, nifedipine, and
lidocaine than the MCP artery. These differences in sensitivity to
vasoconstrictors and vasodilators between the human MCP artery and vein
lend support to the clinical impression that, in cutaneous and
musculocutaneous flap surgery, veins appear to be more susceptible to
vasospasm than do arteries and, once established, venous vasospasm seems to be more difficult to resolve than arterial vasospasm.
| |
ACKNOWLEDGEMENTS |
The authors thank Tina Ferri for word processing in preparation of
this manuscript.
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FOOTNOTES |
This research project was supported by an operating grant (MT 8048) to
C. Y. Pang from the Medical Research Council of Canada.
Address for reprint requests and other correspondence: C. Y. Pang, The Hospital for Sick Children, 555 Univ. Ave., Toronto, Ontario, Canada M5G 1X8 (E-mail: pang{at}sickkids.on.ca).
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 23 May 2000; accepted in final form 21 July 2000.
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