Acute and sustained effects of vascular endothelial growth factor on survival of flaps and skin grafts.

Over the past 15 years, we have completed 10 experimental studies of the effects of vascular endothelial growth factor (VEGF) on the survival of flaps and skin grafts. We have reviewed these studies to summarize evidence for 2 distinct phases of VEGF actions. The 10 studies were reviewed and classified as demonstrating acute VEGF effects (with VEGF administered at the time of procedures) or sustained VEGF effects (with VEGF administered 24 hours or more before procedures). Acute effects of VEGF included increased survival of skin flaps, muscle flaps, and full thickness skin grafts, increased viability markers in hind limb replants, selective cytokine suppression, and variable modulation of nitric oxide synthase expression. Sustained VEGF effects included extension of skin flap territories, accelerated maturation of tubed pedicle flaps, and increased neovascularization. VEGF effects coincide with descriptive mechanisms of tissue survival. The acute VEGF effects of tissue edema and vasodilation parallel serum imbibition and inosculation. The sustained VEGF effect of neovascularization may be mechanisms of permanent tissue survival at new sites, as well as delay phenomena. Manipulation of these VEGF effects could lead to strategies for achieving greater predictability in flap and graft survival.