The goal of this investigation is to determine the role of the blood/materials interaction in prosthetic arterial graft thrombosis. The relationship between baseline host platelet responsiveness, acute phase reactivity to the prosthetic graft and chronic reactivity to graft thrombosis and anastomotic hyperplasia will be determined. We have developed a dog model with a long prosthetic arterial graft (50.0 cm) designed for simple subcutaneous arterial blood sampling. We will simultaneously collect samples as blood enters the prosthetic artery and 50.0 cm distal in the conduit over extended time periods (months). This provides for a comprehensive study of events over time that occur in blood on a single pass through the conduit. The following blood components will be examined: 1) platelets; platelet count, mean platelet volume, platelet aggregation and degranulation studies, platelet survival studies, thromboxane B2 release, and transforming growth B1, 2) white blood cells; wbc count, differential, 3) complete blood count; RBC, MCV, hematocrit, 4) thrombin activity; fibrinopeptide A production, 5) plasmin activity, fibrin (ogen) degradation products. The grafts will be removed after eight months implantation and histologically examined using light, scanning and transmission electron microscopy. Pre-clotted knitted Dacron arterial grafts will be studied. The blood/materials interaction will be altered through the use of Ticlopidine and by chronic intra-arterial infusion of r-hirudin. This transformation will improve understanding of the mechanism of arterial graft thrombosis. It will provide a basis for selection of patients, modification of materials, and approaches to drug intervention.
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