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J Reconstr Microsurg 2006; 22(2): 129-136
DOI: 10.1055/s-2006-932508
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Intramuscular Administration of Vascular Endothelial Growth Factor Augmenting Collateral Circulation in a Rat Hindlimb Replantation Model

Feng Yuan1 , Guang-Rong Yu1 , Shi-Min Chang1 , William C. Lineaweaver2 , Feng Zhang2
  • 1Department of Orthopedic Surgery, Tongji Hospital, Tongji University, Shanghai, China
  • 2Division of Plastic Surgery, The University of Mississippi Medical Center, Jackson, MS, USA
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Publikationsverlauf

Accepted: October 25, 2005

Publikationsdatum:
03. Februar 2006 (online)

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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
    CrossrefPubMedSuche in Google Scholar
  • 2 Strauch B, Terzis J K. Replantation of digits.  Clin Orthop. 1978;  133 35-38
    PubMedSuche in Google Scholar
  • 3 Yoshimura M, Nomura S, Ueno T et al.. Clinical replantation of digits and its problems.  Ann Acad Med Singapore. 1982;  11 218-224
    PubMedSuche in Google Scholar
  • 4 Harris G D, Finseth F, Buncke H J. The hazard of cigarette smoking following digital replantation.  J Microsurg. 1980;  1 403-404
    PubMedSuche in Google Scholar
  • 5 Arakaki A, Tsai T M. Thumb replantation: survival factors and re-exploration in 122 cases.  J Hand Surg. 1993;  18B 152-156
    PubMedSuche in Google Scholar
  • 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
    Suche in Google Scholar
  • 7 Sabovic M. Treatment of chronic ischaemia of a replanted thumb with iloprost.  J Hand Surg. 2002;  27 481-483
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    Suche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    Thieme ConnectPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 29 Zachary I. Vascular endothelial growth factor.  Int J Biochem Cell Bio. 1998;  30 1169-1174
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 32 Baumgartner I, Pieczek A, Manor O et al.. Constitutive expression of phVEGF165 in patients with critical limb ischemia.  Circulation. 1998;  97 1114-1123
    CrossrefPubMedSuche in Google Scholar
  • 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
    CrossrefPubMedSuche in Google Scholar
  • 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
    Thieme ConnectPubMedSuche in Google Scholar
  • 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
    PubMedSuche in Google Scholar

Feng ZhangM.D. Ph.D. 

Division of Plastic Surgery, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216