EFFECTS OF ANGIOGENESIS FACTORS ON SKIN FLAP SURVIVAL

IN SPITE OF THE COMMON USE OF SKIN GRAFTS AND SKIN FLAPS IN PLASTIC AND RECONSTRUCTIVE SURGERY, SERIOUS COMPLICATIONS STILL ARISE. THE COMPLETE OR PARTIAL NECROSIS THAT CAN OCCUR IN SURGICAL FLAPS OR GRAFTS IS DUE TO PROLONGED TISSUEISCHEMIA THAT COMPROMISES TISSUE BLOOD FLOW. PROMPT REVASCULARIZATION OF THE GRAFT OR FLAP BY ANASTOMOSES AND NEOVASCULARIZATION IS A MAJOR DETERMINANT OF THE SUCCESS OF GRAFT/FLAP SURGERY. IN THIS RESEARCH, THREE ANGIOGENIC AGENTS WILL BE EXAMINED FOR THEIR EFFECTS ON SKIN-FLAP SURVIVAL: (1) ADENOSINE, A PRODUCT OF ISCHEMIC METABOLISM, (2) A LOW-MOLECULAR-WEIGHT, TUMOR-DERIVED FACTOR, AND (3) A POLYPEPTIDE ANGIOGENESIS FACTOR, BASIC FIBROBLAST GROWTH FACTOR. TEST MATERIALS AT VARIOUS DOSAGES WILL BE APPLIED TO PEDICLE SKIN FLAPS ON RATS USING INFUSION, SUFFUSION, AND/OR SUBCUTANEOUS INJECTIONS THAT WILL BE ADMINISTERED AT THE TIME OF SURGERY,PREOPERATIVELY, AND/OR POSTOPERATIVELY. THE RESULTS OF THESE STUDIES WILL BE ANALYZED WITH REGARD TO EFFECTS ON FLAP NECROSIS AND SURVIVABILITY. SELECTED SPECIMENS WILL BE EXAMINED HISTOLOGICALLY FOR EFFECTS ON FLAP VASCULATURE AS WELL AS ON OTHER FEATURES OF THE REPAIR PROCESS. THESE PHASE I STUDIES WILL DETERMINE THE FEASIBILITY OF EMPLOYING ANGIOGENIC AGENTS IN AUGMENTING SKIN-FLAP SURVIVAL. FAVORABLE RESULTS WILL HAVE RELEVANCE FOR SKIN-GRAFT SURGERY AS WELL AS THE TREATMENT OF OTHER WOUND TYPES.