SUMMARY

Atherothrombosis can induce acute myocardial infarction and stroke through a catastrophic chain of events. Atherosclerotic lesions form a stenosis in the blood flow, thereby modifying hemodynamics normally found in the vessel, which has been found to promote thrombus growth. Thrombosis involves initial platelet adhesion to the subendothelium of a ruptured atherosclerotic lesion, with subsequent aggregation of additional platelets, ending in fatal occlusion in some cases. The process of platelet binding, platelet transport, and platelet activation have all been shown to depend on shear. Clinical atherothrombotic occlusions occur under high shear with accumulation of millions of platelets over 30 minutes. Most previous studies do not capture the pathologic process of occlusion and instead focus on the first 5 minutes of hundreds of platelets attaching under low shear. This study will quantify the range of pathologic shear stress created by varying degrees of stenoses under pathophysiological flow and pressure conditions using computational fluid dynamics (CFD). Shear rates and growth rates will be determined spatially along a stenosis with respect to time to characterize the thrombus growth relation to shear as thrombus nears occlusion. Mural platelet activation, hypothesized to be necessary for rapid platelet accumulation will be evaluated by comparing thrombus growth rates at different activation conditions. Activation will be blocked through Prostaglandin E to determine if rapid platelet accumulation can be blocked. Activation will subsequently be promoted by infusing ADP into whole blood to induce rapid platelet accumulation. Finally, platelet transport rates affected by shear Enhanced Diffusivity and platelet margination will be predicted through CFD and compared to maximal thrombus growth rates in the experiments to determine if platelet transport rates may limit thrombus growth rates for a particular range of shear.