Expansion of Surviving Skin Paddle of Neurocutaneous Island Flaps in Rats by VEGF

ABSTRACT

The purpose of this study was to investigate whether vascular endothelial growth factor (VEGF) can enlarge the skin paddles of neurocutaneous flaps in rats. Wistar albino rats were used in four groups: Group 1, (n = 10): neurocutaneous island flap; Group 2, (n = 10): neurocutaneous island flap, surgical delay; Group 3, (n = 10): neurocutaneous island flap, VEGF; Group 4, (n = 10): graft. A 3 × 3-cm, neurocutaneous island flap was elevated on the anterolateral skin of the thigh of the rats. The surviving flap areas were 29.7 ± 1.43 percent in Group 1, 41.3 ± 3.24 percent in Group 2, 94.2 ± 1.46 percent in Group 3. There were no surviving areas in Group 4. The vascular networks of Group 3 animals were more intensive and diffused on microangiography and the histopathologic findings were better in this group. The surviving flap areas in Group 3 animals were enlarged approximately three times over the original size.

KEYWORDS

VEGF - flap - neurocutaneous - paddle expansion

REFERENCES

• 1 Padubidri A, Browne Jr E. 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
• 2 Keck P J, Hauser S D, Krivi G et al.. Vascular permeability factor, an endothelial cell mitogen related to PDGF.  Science. 1989;  246 1309-1312
• 3 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
• 4 Tsurumi Y, Kearney M, Chen D et al.. Treatment of acute limb ischemia by intramuscular injection of vascular endothelial growth factor gene.  Circulation. 1997;  96 382-388
• 5 Zhang F, Fischer K, Komorowska-Timek E, Guo M, Cui D, Dorsett-Martin W, Buncke H J, Lineaweaver W C. Improvement of skin paddle survival by application of vascular endothelial growth factor in a rat TRAM flap model.  Ann Plast Surg. 2001;  46 314-319
• 6 Connolly D T, Heuvelman D M, Nelson R et al.. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.  J Clin Invest. 1989;  359 1470-1478
• 7 Gurunluoglu R, Bayramicli M, Sonmez A, Numanoglu A. A neurocutaneous island flap model: an experimental study in rats.  Ann Plast Surg. 2000;  44 53-58
• 8 Quenu J, Lejars F. Etude sur les vaisseaux sanguins des nerfs.  Arch Neurol. 1892;  XXIII 1-33
• 9 Salmon M. Les Arteres de la Peau. Paris; Masson 1936: 1-122
• 10 Bertelli J A. Neurocutaneous axial island flaps in the forearm: anatomical, experimental and preliminary clinical results.  Br J Plast Surg. 1993;  46 489-496
• 11 Shalaby H A, Saad M A. The venous island flap: is it purely venous?.  Br J Plast Surg. 1993;  46 285-287
• 12 Schott R J, Morrow L A. Growth factor and angiogenesis.  Cardiovas Res. 1993;  27 1155-1161
• 13 Folkman J, Klagsbrun M. Angiogenetic factors.  Science. 1987;  235 442-447
• 14 Jakeman L B, Winer J, Bennett G L, Altar C A, Ferrara N. Binding sites for vascular endothelial growth factor are localised on endothelial cells in adult rat tissues.  J Clin Invest. 1992;  89 244-253
• 15 Leung D W, Cachianes G, Kuang W J, Goeddel D V, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen.  Science. 1989;  246 1306-1309
• 16 Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor.  Endocr Rev. 1997;  18 4-25
• 17 Yang R, Thomas G R, Bunting S et al.. Effects of vascular endothelial growth factor on hemodynamics and cardiac performance.  J Cardiovasc Pharmacol. 1996;  27 838-844
• 18 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
• 19 Zachary I. Vascular endothelial growth factor.  Int J Biochem Cell Biol. 1998;  30 1169-1174
• 20 Shima D T, Deutsch U, D'Amore P A. Hypoxic induction of VEGF in human epithelial cells is mediated by increases in mRNA stability.  FEBS Lett. 1995;  370 203-208
• 21 Takeshita S, Zheng L P, Brogi E et al.. Therapeutic angiogenesis. A single intraarteriel bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model.  J Clin Invest. 1994;  93 662-670
• 22 Takeshita S, Pu L Q, Stein L A et al.. Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia.  Circulation. 1994;  90 II228-II234
• 23 Taub P J, Marmur J D, Zhang W X et al.. Locally administered vascular endothelial growth factor cDNA increases survival of ischemic experimental skin flaps.  Plast Reconstr Surg. 1998;  102 2033-2039
• 24 Lantieri L A, Martin-Garcia N, Wechsler J, Mitrofanoff M, Raulo Y, Baruch J P. Vascular endothelial growth factor expression in expanded tissue: a possible mechanism of angiogenesis in tissue expansion.  Plast Reconstr Surg. 1998;  101 392-398
• 25 Lineaweaver W C, Lei M P, Mustain W, Oswald T M, Cui D, Zhang F. Vascular endothelial growth factor, surgical delay, and skin flap survival.  Ann Surg. 2004;  6 866-873
• 26 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
• 27 Seify H, Bilkay U, Jones G. Improvement of TRAM flap viability using human VEGF-induced angiogenesis: a comparative study of delay techniques.  Plast Reconstr Surg. 2003;  112 1032-1039
• 28 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 Plas Surg. 1999;  43 172-178
• 29 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
• 30 Lubiatowski P, Goldman C K, Gurunluoglu R, Carnevale K, Siemionow M. Enhancement of epigastric skin flap survival by adenovirus-mediated VEGF gene therapy.  Plast Reconstr Surg. 2002;  109 1986-1993
• 31 Zhang F, Richards L, Angel M F et al.. Accelerating flap maturation by vascular endothelial growth factor in a rat tube flap model.  Br J Plast Surg. 2002;  55 59-63