Effect of Time on the Viability of Ischemic Skin Flaps Treated with Vascular Endothelial Growth Factor (VEGF) cDNA

ABSTRACT

This study examined the efficacy of gene therapy on wound healing. The authors investigated whether delivery of the gene encoding a particular cytokine, known to be important in angiogenesis, could affect ischemic skin flaps. Anterior abdominal skin flaps, based solely on the epigastric artery and vein, were created in the Sprague-Dawley rat model. At the time of elevation, the arterial pedicle supplying each flap was infused either with the gene for vascular endothelial growth factor (VEGF) or physiologic saline alone. The flaps were resutured into place and observed for a period of either 4 or 3 days, at which time the pedicle was ligated. Twenty minutes following ligation, blood flow in the flaps was measured by dye fluorescence. Tissue viability of the flaps was subsequently measured by planimetry after a period of 7 days. Flaps that received the VEGF gene and were ligated at 4 days had an average dye fluorescence index (DFI) of 31.1 following ligation, and 93.9 percent viable tissue after 7 days. Flaps that received saline alone, and were ligated following a similar interval, had an average DFI of 14.0 and 31.9 percent viable tissue. Among the subjects that were ligated at 3 days, only a single, gene-infused flap had any noticeable viable tissue after 7 days. The DFI of these groups was 11.0 for the gene-infused group and 22.1 for the saline-infused group. The results suggest that delivery of the gene for VEGF can improve the survival of ischemic skin flaps, but that the effect of gene therapy is not limitless.