The effect of single administration of vascular endothelial growth factor or l-arginine on necrosis and vasculature of the epigastric flap in the rat model

Objectives. Vascular endothelial growth factor (VEGF) and nitric oxide (NO) produce vasodilation, induce angiogenesis, and improve survival of surgical flaps. We used the rat epigastric skin flap to study the effect of a single intra-arterial dose of VEGF or l-arginine, a substrate for NO production, on flap regional necrosis and pedicle dependence of flap perfusion. Methods. In 30 Sprague-Dawley rats an 8×8 cm 2 skin flap, consisting of four vertical zones marked A through D (right to left), based on the proximal right inferior epigastric vessels was raised. Subsequently, 1 ml of either saline (control, n=10), 5 μg VEGF (VEGF, n=10), or 50 mg of l-arginine ( l-arginine, n=10) was injected into the arterial pedicle by cannulating the right saphenous artery, and the flap was resutured in place. After 8 days, the animals were perfused systemically with 15 μm coloured fluorescent microspheres before (blue) and after (yellow-green) ligation of the right inferior epigastric vascular pedicle. After sacrifice, the area of flap necrosis was measured in each zone by templates and weight-to-surface ratio, and the flap zones were harvested and processed for determination of fluorescence and blood flow. Results. Administration of VEGF or l-arginine resulted in decreased total and regional (zone D) flap necrosis (ANOVA