The purpose of this proposal is to establish the in vivo efficacy of a new class of thrombin inhibitors, thrombostatins. Thrombostatins are a group of agents that prevent alpha and gamma thrombus from activating platelets. Thrombostatins prevent thrombin from activating platelets by preventing thrombin from leaving its receptors. A particular thrombostatin specificity for thrombin's cloned receptors. Thrombostatins represent a new generation of thrombin inhibitors. Such an agent is needed because potent and specific agents which have directed to thrombin itself, have been associated with too much hemorrhage in clinical trials. The goal of this study is to show thrombostatins in vivo efficacy to prevent thrombosis in adult coronary arteries thrombosis model as a single agent or in combination with aspirin. The applicants theorized that this study will create a new class of selected thrombin inhibitors which alone or in combination with other platelet inhabitant agents potential inhibition of thrombosis in the coronary arteries. Such an agent is needed since all present anti-coagulant regimens only achieve a 25 to 40% reduction in adverse advance in acute coronary artery syndromes.
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