Effects of Sympathetic Denervation and Oxygen Free Radicals on Neovascularization in Skin Flaps

Abstract

An island skin flap, with its sole blood supply based on the inferior epigastric vessels, in Sprague-Dawley rats (female, 220 to 250 gm) was used as a model for the investigation of neovascularization. Flap survival after pedicle ligation was considered an indicator of neovascularization. Vascular pedicles were ligated on days 2 to 5 after flap elevation, and the time course of neovascularization in the innervated and denervated flaps was determined by measurements of survival on day 7 after pedicle ligation (on days 9 to 12 postoperatively). Neovascularization sufficient to maintain viability was established at 4 and 5 days after flap elevation in the innervated and denervated flaps, respectively. The effects of various scavengers of oxygen free radicals on neovascularization were evaluated in the innervated and denervated flaps. The pedicles were ligated 3 days after flap elevation. Flap survival was assessed on day 7 after pedicle ligation (on day 10 postoperatively). Treatment with a single dose of deferoxamine (50 mg/kg) increased the viability from 48 to 69 percent of flap area in the denervated flaps (p < 0.01) but produced little effect on viability in the innervated flaps. In the denervated flaps, treatments with a single dose of superoxide dismutase, intravenously and intraarterially, also substantially increased the survival rates from 29 to 86 percent (marginally significant) and 100 percent (p < 0.05), respectively. Allopurinol improved the survival from 43 to 88 percent; the difference was not statistically significant. The results suggest that denervation resulted in a delay of neovascularization and that severe sympathetic denervation contributes to the production of oxygen free radicals, which may exert their inhibitory effects on neovascularization.