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Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: efficacy and mechanism.

Publication ,  Journal Article
Khan, A; Ashrafpour, H; Huang, N; Neligan, PC; Kontos, C; Zhong, A; Forrest, CR; Pang, CY
Published in: Am J Physiol Regul Integr Comp Physiol
November 2004

Distal skin ischemic necrosis is a common complication in skin flap surgery. The pathogenesis of skin flap ischemic necrosis is unclear, and there is no clinical treatment available. Here, we used the 4 x 10 cm rat dorsal skin flap model to test our hypothesis that subcutaneous injection of vascular endothelial growth factor 165 (VEGF165) in skin flaps at the time of surgery is effective in augmentation of skin flap viability, which is associated with an increase in nitric oxide (NO) production, and the mechanism involves 1) an increase in skin flap blood flow in the early stage after surgery and 2) enhanced angiogenesis subsequently to sustain increased skin flap blood flow and viability. We observed that subcutaneous injection of VEGF165 in skin flaps at the time of surgery increased skin flap viability in a dose-dependent manner. Subcutaneous injection of VEGF165 at the dose of 2 microg/flap increased skin flap viability by 28% (P < 0.05; n = 8). Over 80% of this effect was blocked by intramuscular injection of the NO synthase (NOS) inhibitor Nomega-nitro-L-arginine (13 mg/kg) 45 min before surgery (P < 0.05; n = 8). The VEGF165 treatment also increased skin flap blood flow (2.68 +/- 0.63 ml x min(-1) x 100 g(-1)) compared with the control (1.26 +/- 0.10 ml x min(-1) x 100 g(-1); P < 0.05, n = 6) assessed 6 h postoperatively. There was no change in skin flap capillary density at this time point. VEGF165-induced increase in capillary density (32.2 +/- 1.1 capillaries/mm2; P < 0.05, n = 7) compared with control (24.6 +/- 1.4 capillaries/mm2) was seen 7 days postoperatively. There was also evidence to indicate that VEGF165-induced NO production in skin flaps was stimulated by activation of NOS activity followed by upregulation of NOS protein expression. These observations support our hypothesis and for the first time provide an important insight into the mechanism of acute local VEGF165 protein therapy in mitigation of skin flap ischemic necrosis.

Duke Scholars

Published In

Am J Physiol Regul Integr Comp Physiol

DOI

ISSN

0363-6119

Publication Date

November 2004

Volume

287

Issue

5

Start / End Page

R1219 / R1229

Location

United States

Related Subject Headings

  • Vasodilation
  • Vascular Endothelial Growth Factor A
  • Surgical Flaps
  • Skin
  • Regional Blood Flow
  • Rats, Sprague-Dawley
  • Rats
  • Prostaglandin-Endoperoxide Synthases
  • Physiology
  • Nitric Oxide Synthase Type III
 

Citation

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MLA
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Khan, A., Ashrafpour, H., Huang, N., Neligan, P. C., Kontos, C., Zhong, A., … Pang, C. Y. (2004). Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol, 287(5), R1219–R1229. https://doi.org/10.1152/ajpregu.00143.2004
Khan, Asim, Homa Ashrafpour, Ning Huang, Peter C. Neligan, Christopher Kontos, Anguo Zhong, Christopher R. Forrest, and Cho Y. Pang. “Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: efficacy and mechanism.Am J Physiol Regul Integr Comp Physiol 287, no. 5 (November 2004): R1219–29. https://doi.org/10.1152/ajpregu.00143.2004.
Khan A, Ashrafpour H, Huang N, Neligan PC, Kontos C, Zhong A, et al. Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol. 2004 Nov;287(5):R1219–29.
Khan, Asim, et al. “Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: efficacy and mechanism.Am J Physiol Regul Integr Comp Physiol, vol. 287, no. 5, Nov. 2004, pp. R1219–29. Pubmed, doi:10.1152/ajpregu.00143.2004.
Khan A, Ashrafpour H, Huang N, Neligan PC, Kontos C, Zhong A, Forrest CR, Pang CY. Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol. 2004 Nov;287(5):R1219–R1229.

Published In

Am J Physiol Regul Integr Comp Physiol

DOI

ISSN

0363-6119

Publication Date

November 2004

Volume

287

Issue

5

Start / End Page

R1219 / R1229

Location

United States

Related Subject Headings

  • Vasodilation
  • Vascular Endothelial Growth Factor A
  • Surgical Flaps
  • Skin
  • Regional Blood Flow
  • Rats, Sprague-Dawley
  • Rats
  • Prostaglandin-Endoperoxide Synthases
  • Physiology
  • Nitric Oxide Synthase Type III