Thromboembolic complications and abnormal bleeding are among the major complications of valvular heart disease, artificial heart valves, cardiopulmonary bypass and ventricular assist devices. The mechanisms by which platelets and the blood coagulation system are activated in these conditions are incompletely understood. There is evidence that both interaction of platelets with foreign surfaces or the diseased vasculature and effects of fluid shear stress are involved in the activation of platelets and that these processes can be modified by red blood cells (RBC) and products of the vessel wall. The studies proposed here are designed to examine in detail: 1. The mechanisms by which well-defined, uniform, laminar fluid shear stress (in the range that may be encountered in vivo) triggers platelet reactions (release of platelet granule contents, platelet aggregation, platelet procoagulant availability) and causes platelet damage; 2. The effects of exposure of normal platelets and """"""""hypersensitive"""""""" platelets (from patients with conditions associated with premature atherosclerotic disease) to both prolonged, steady, and to biologically more relevant, repetitive short-term shear stresses on in vitro function and in vivo survival; 3. The effects of normal and abnormal (impaired deformability, abnormal size) RBC on shear-induced platelet alterations; 4. The effects of normal and abnormal (atherosclerotic) vascular surfaces on platelet reactions in laminar shear flow. The results of these studies should provide important basic information in regard to the responses of platelets to fluid shear stress in vitro and vivo and may aid in the development of better strategies for both prevention and treatment of thrombotic and hemorrhagic complications with artificial cirulatory devices and atherosclerosis.
