LOCALLY ADMINISTERED VASCULAR ENDOTHELIAL GROWTH-FACTOR CDNA INCREASES SURVIVAL OF ISCHEMIC EXPERIMENTAL SKIN FLAPS

Microvascular surgery has emerged as an attractive area for recent adv ances in the field of gene therapy. The present study investigated the survival of ischemic, experimental skin naps after treatment with the gene encoding vascular endothelial growth factor (VEGF). In 30 Spragu e-Dawley rats, anterior abdominal skin flaps supplied by the epigastri c artery and vein were created. Ten animals were treated with a mixtur e of liposomes and the cDNA encoding the 121-amino acid isoform of VEG F. Another 10 animals were treated with control plasmid DNA and liposo me transfection medium; a third group of 10 animals was given physiolo gic saline. Each solution was injected directly into the femoral arter y distal to the origin of the epigastric pedicle supplying the flap. F our days after injection, the pedicle was ligated and blood flow in th e flap was approximated using dye fluorescence. Seven days later, the amount of viable tissue within the flap was measured by planimetry. Af ter the animals were killed, specimens fi-om both the operated and non operated sides of the abdomen were harvested for immunohistologic evid ence of VEGF protein expression. Average dye fluorescence indices of t he three groups (VEGF cDNA, control plasmid, and saline) 2 hours after pedicle ligation were 35.9, 23.9, and 53.9 percent, respectively (p < 0.05). Compared with the two control groups, flaps receiving VEGF cDN A had significantly greater tissue viability at the end of 7 days: 93. 9 versus 28.1 percent for the control plasmid DNA group and 31.9 perce nt for the saline group (p < 0.05). Immunohistochemical staining docum ented increased deposition of VEGF protein in flaps that were infused with the VEGF cDNA versus saline alone (p < 0.05). The results indicat ed that the survival of ischemic tissues can be enhanced by administra tion of a cDNA encoding VEGF, a protein known to be important in the p rocess of angiogenesis and wound healing.