Purpose: Partial necrosis of pedicle skin flaps, believed to be due to inadequate blood perfusion and ischemia-reperfusion injury, remains a significant problem in plastic and reconstructive surgery. Recently, the potential of therapeutic agents such as a variety of growth factors to improve the viability of ischemic skin flaps has aroused considerable interests. Vascular endothelial growth factor (VEGF), a heparin-binding glycoprotien, is a potent endogenous stimulator of both angiogenesis and vascular permeability. In this study, we examined the effect of exogenous VEGF on ischemic flap survival and on the regulation of cytokines in a rat skin flap model.

Methods: Fifty-eight male Sprague-Dawley rats were used. A caudally based dorsal musculocutaneous flap, measuring 3 x 10 cm, was the flap model. The study was divided into two parts. In part I, exogenous VEGF (1 mg/mL) was injected subdermally into the flaps in 14 rats before the flaps were sutured back in place. The same number of rats with flaps received saline injection and served as the control. The skin paddle survival was measured five days postoperatively. In part II, biopsies were taken from the flaps treated with VEGF and saline. Biopsies were obtained at 2.5, 5.5, and 8.5 cm from the distal edge at 12 and 24 hours after the flaps were sutured. Gene expressions of IGF-1, TGF-b, bFGF, PDGF, IL-1, TNF-a, and inducible nitric oxide synthase (iNOS) were measured.

Results: Subdermal injection of exogenous VEGF to the flap could induce angiogenesis and significantly improve survival of the flap (89% of the total skin paddle, p<0.05) compared to the control group (64% survival, p<0.05). The expressions of TNF-a&#61537; and iNOS in the distal part of the flap treated with VEGF were significantly decreased in comparison to the control group at 12 and 24 hours postoperatively.

Conclusion: Administration of exogenous VEGF can significantly enhance survival of ischemic flaps. VEGF can also protect the flap from ischemia-reperfusion injury through the regulation of proinflammatory cytokines and inhibition of cytotoxic nitric oxide production.