HIRUDIN IMMOBILIZATION TO PRODUCE ANTITHROMBIC SURFACES

ALL POLYMERS USED FOR IMPLANT DEVICES THAT CONTACT BLOOD ARETHROMBOGENIC, AND NO CURRENT SURFACE TREATMENTS ARE SATISFACTORY. THIS PROJECT PROPOSES TO USE A RECENTLY CHARACTERIZED PEPTIDE, HIRUDIN, TO DEVELOP A SUPERIOR ANTITHROMBIC SURFACE TREATMENT. HIRUDIN IS ONE OF THE MOST POTENT ANTITHROMBIC AGENTS KNOWN. IT ACTS BY BINDING TENACIOUSLY TO THROMBIN AND INHIBITING BOTH MAJOR THROMBIN ACTIVITIES: (1) PLATELET ACTIVATION AND (2) PROTEOLYTIC ACTIVITIES THAT LEAD TO FIBRIN COAGULATION. IMMOBILIZATION TECHNOLOGY WILL BE USED TO COVALENTLY IMMOBILIZE HIRUDIN ONTO SILICONE RUBBER AND POLYURETHANE. THEN THE HIRUDIN-COATED POLYMERS WILL BE ASSAYED FOR THROMBIN-BINDING ACTIVITY, PROTEOLYTIC ACTIVITY OF BOUND THROMBIN, AND PLATELET ADHESION. PHASE II STUDIES WILL COMPARE HEPARIN TO HIRUDIN AS ANTITHROMBIC SURFACE TREATMENTS AND WILL EVALUATE THE EFFICACY OF THESE TREATMENTS IN EX VIVO SHUNT AND IN VIVO BLOOD COMPATIBILITY ASSAYS. SUCCESSFUL COMPLETION OF THIS PROJECT IS EXPECTED TO PRODUCE SUPERIOR ANTITHROMBIC SURFACETREATMENTS FOR DEVICES THAT ARE PLACED IN CONTACT WITH BLOOD.