ABSTRACT
This study evaluated the effect of exogenous vascular endothelial growth factor (VEGF)
on augmentation of collateral circulation in a rat hindlimb replantation model. Twenty-eight
rats, divided into four groups, underwent right hindlimb replantation. In experimental
Group 1, the rats received daily intramuscular VEGF injections (1 μg/kg). In Group
2, the rats received 25 μg/kg VEGF injections. In Group 3, the rats received 50 μg/kg
VEGF injections. In Group 4, the control group, rats received saline injections. Seven
days after replantation, the repaired femoral vessels were excised. Seven days after
excision of the femoral vessels, toe necrosis ratios of the replanted hindlimbs were
grossly examined, and calf blood pressures were measured. Angiography was performed
and muscle tissue was biopsied for histology. The results showed that administration
of VEGF significantly decreased toe necrosis and improved calf blood pressure ratio,
angiographic score, and capillary density in the replanted hindlimbs that underwent
late vessel excision. The effect of VEGF was significantly dose-dependent. The authors
conclude that VEGF can augment angiogenesis and collateral vessel formation in replanted
limbs, and improve survival in replanted limbs with potential late arterial insufficiency.
KEYWORDS
Vascular endothelial growth factor (VEGF) - collateral circulation - limb replantation
- rat model
REFERENCES
- 1
Kleinert H E, Jablon M, Tsai T M.
An overview of replantation and results of 347 replants in 245 patients.
J Trauma.
1980;
20
390-398
- 2
Strauch B, Terzis J K.
Replantation of digits.
Clin Orthop.
1978;
133
35-38
- 3
Yoshimura M, Nomura S, Ueno T et al..
Clinical replantation of digits and its problems.
Ann Acad Med Singapore.
1982;
11
218-224
- 4
Harris G D, Finseth F, Buncke H J.
The hazard of cigarette smoking following digital replantation.
J Microsurg.
1980;
1
403-404
- 5
Arakaki A, Tsai T M.
Thumb replantation: survival factors and re-exploration in 122 cases.
J Hand Surg.
1993;
18B
152-156
- 6
Duffy Jr F J, Concannon M J, Gan B S, May Jr J W.
Late digital replantation failure: pathophysiology and risk factors.
Ann Plast Surg.
1998;
40
538-541
- 7
Sabovic M.
Treatment of chronic ischaemia of a replanted thumb with iloprost.
J Hand Surg.
2002;
27
481-483
- 8
Leung D W, Cachianes G, Kuang W J et al..
Vascular endothelial growth factor is a secreted angiogenic mitogen.
Science.
1989;
246
1306-1309
- 9
Takeshita S, Zheng L P, Brogi E et al..
Therapeutic angiogenesis: a single intraarterial bolus of vascular endothelial growth
factor augments revascularization in a rabbit ischemic hind limb model.
J Clin Invest.
1994;
93
662-670
- 10
Takeshita S, Isshiki T, Sato T.
Increased expression of direct gene transfer into skeletal muscles observed after
acute ischemic injury in rats.
Lab Invest.
1996;
74
1061-1065
- 11
Takayuki A, Christophe B, Zheng L P et al..
Synergistic effect of vascular endothelial growth factor and basic fibroblast growth
factor on angiogenesis in vivo.
Circulation.
1995;
92
365-371
- 12
Bauters C, Asahara T, Zheng L P et al..
Recovery of disturbed endothelium-dependent flow in the collateral-perfused rabbit
ischemic hindlimb after administration of vascular endothelial growth factor.
Circulation.
1995;
91
2802-2809
- 13
Becit N, Ceviz M, Kocak H et al..
The effect of vascular endothelial growth factor on angiogenesis: an experimental
study.
Eur J Vascular Endovasc Surg.
2001;
22
310-316
- 14
Walder C E, Errett C J, Bunting S et al..
Vascular endothelial growth factor augments muscle blood flow and function in a rabbit
model of chronic hindlimb ischemia.
J Cardiovasc Pharmacol.
1996;
27
91-98
- 15
Hershey J C, Baskin E P, Corcoran H A et al..
Vascular endothelial growth factor stimulates angiogenesis without improving collateral
blood flow following hindlimb ischemia in rabbits.
Heart Vessels.
2003;
18
142-149
- 16
Takeshita S, Isshiki T, Mori H et al..
Use of synchrotron radiation microangiography to assess development of small collateral
arteries in a rat model of hindlimb ischemia.
Circulation.
1997;
95
805-808
- 17
Takeshita S, Isshiki T, Mori H et al..
Microangiographic asssessment of collateral vessel formation following direct gene
transfer of vascular endothelial growth factor in rat.
Cardio Res.
1997;
35
547-552
- 18 Zhang F, Lineaweaver W C, Kao S D, Walker R, Tonken H P. Manual of Experimental
Muscle Flap and Organ Transplantation Models in the Rat. Reading, PA; Sharepoint Surgical
Specialties Corporation 1995: 60-66
- 19
Black M J, Chait L, O'Brien B M, Sykes P J, Sharzer L A.
How soon may the axial vessels of a surviving free flap be safely ligated: a study
in pigs.
Br J Plast Surg.
1978;
31
295-299
- 20
Oliva A, Lineaweaver W C, Buncke H J et al..
Salvage of wounds following failed tissue transplantation.
J Reconstr Microsurg.
1993;
9
257-263
- 21
Kroll S S, Schusterman M A, Reece G P et al..
Timing of pedicle thrombosis and flap loss after free-tissue transfer.
Plast Reconstr Surg.
1996;
98
1230-1233
- 22
Griffin P A, Tan E, Katsaros J.
Late arterial thrombosis in a replanted thumb: a case report.
J Reconstr Microsurg.
1989;
5
75-77
- 23
Zhang F, Lei M P, Oswald T M et al..
The effect of vascular endothelial growth factor on the healing of ischaemic skin
wounds.
Br J Plast Surg.
2003;
56
334-341
- 24
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
- 25
Kryger Z, Zhang F, Dogan T, Cheng C, Lineaweaver W C, Buncke H J.
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
- 26
Pang Y, Lineaweaver W C, Lei M P et al..
Evaluation of the mechanism of vascular endothelial growth factor improvement of ischemic
flap survival in rats.
Plast Reconstr Surg.
2003;
112
556-564
- 27
Kryger Z, Dogan T, Zhang F et al..
Effects of VEGF administration following ischemia on survival of the gracilis muscle
flap in the rat.
Ann Plast Surg.
1999;
43
172-178
- 28
Zhang F, Liu H, Stile F et al..
Effect of vascular endothelial growth factor on rat Achilles tendon healing.
Plast Reconstr Surg.
2003;
112
1613-1619
- 29
Zachary I.
Vascular endothelial growth factor.
Int J Biochem Cell Bio.
1998;
30
1169-1174
- 30
Shima D T, Deutsch U, D'Amore P A.
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
- 31
Isner J M, Walsh K, Symes J et al..
Arterial gene therapy for therapeutic angiogenesis in patients with peripheral artery
disease.
Circulation.
1995;
91
2687-2692
- 32
Baumgartner I, Pieczek A, Manor O et al..
Constitutive expression of phVEGF165 in patients with critical limb ischemia.
Circulation.
1998;
97
1114-1123
- 33
Lineaweaver W C, Lei M P, Mustain W, Oswald T M, Cui D, Zhang F.
Vascular endothelium growth factor, surgical delay, and skin flap survival.
Ann Surg.
2004;
239
866-873
- 34
Li Q F, Reis E D, Zhang W X, Silver L, Fallon J T, Weinberg H.
Accelerated flap prefabrication with vascular endothelial growth factor.
J Reconstr Microsurg.
2000;
16
45-49
- 35
Bayati S, Russell R C, Roth A C.
Stimulation of angiogenesis to improve the viability of prefabricated flaps.
Plast Reconstr Surg.
1998;
101
1290-1295
Feng ZhangM.D. Ph.D.
Division of Plastic Surgery, University of Mississippi Medical Center, 2500 North
State Street, Jackson, MS 39216