PROTEIN AND THROMBUS DEPOSITION ON VASCULAR GRAFTS

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The initial response of flowing blood upon contact with a polymer surface is the rapid adsorption of a layer of plasma protein followed by the deposition and activation of platelets. Simple in-vitro experiments suggest that the composition and organization of albumin, fibrinogen, and gamma-globulin in the adsorbed protein layer affect the degree of platelet response. However, more recent studies reveal different protein and platelet deposition patterns from more complex solutions such as plasma and plasma containing red blood cells. Preliminary studies in our laboratories indicate that other plasma agents such as fibronectin and/or von Willebrand factor (vWf) also have a profound effect in inducing in-vivo thrombus formation on surfaces. The research proposed will use an in-vivo procedure to measure the adsorption of plasma proteins and platelets from flowing blood to surfaces of conventional medical polymers and new materials thought to be more thromboresistant. The thrombogenic effect of fibronectin and vWf will be further characterized as well. Small amounts of platelets and/or proteins of interest will be tagged with radioisotopes and injected into canine subjects. Radioactivity adsorbed to the walls of femoral A-V shunts is counted in order to measure platelet deposition and the composition of the adsorbed protein layer. Studies using electron microscopy, ESCA, and binding of radiolabeled antibodies specific to proteins identified in the adsorbed layer are planned to characterize platelet morphology and the nature of the protein layer. These measurements will provide insight into how blood responds to a variety of surfaces in-vivo, how the nature of the protein layer adsorbed in-vivo is related to thrombogenic behavior, and whether other factors are present and active in the protein layer.