FLOW INDUCED PLATELET ACTIVATION IN CARDIOVASCULAR PATHOLOGIES AND DEVICES

0302275 Bluestein The advent of implantable blood recirculating devices has provided life saving solutions to patients with severe cardiovascular diseases and end stage heart disease. Left ventricular assist devices were recently shown to be superior to drug therapy, the implantable total artificial heart is showing promise, and prosthetic heart valves are routinely used for replacing diseased heart valves. However, thromboembolism and the attendant risk of cardioembolic stroke remains an impediment to these devices. The mandatory life-long anticoagulant drug regimen they require does not eliminate this risk. One of the major culprits is the emergence of pathologic flow patterns that enhance the propensity to initiate thromboembolism. The objective of this research project is to develop state-of-the-art numerical and experimental tools in order to elucidate flow-induced mechanisms leading to thromboembolism. Specifically, transient and turbulent numerical simulations will be performed in 3D models of arterial stenoses and blood recirculating devices. Flow patterns that induce platelet activation and enhance platelet aggregation will be quantitatively depicted. Stress histories that may bring platelets past their activation threshold will be computed along pertinent trajectories. A model for platelet activation that takes into account cumulative effects of stress history and senescence will be developed. The model will be tested against in vitro platelet activity measurements using an innovative platelet activity state (PAS) assay that enables real time measurements of platelet hemostatic activity under flow conditions. The PAS measurements will be performed in a system simulating conditions of arterial stenosis and in a model of a cardiovascular device. The first system is an innovative Dynamic Cell Shearing Device (DCSD) capable of reproducing the dynamic aspects of normal and pathologic arterial waveforms with great accuracy. Experiments in the DCSD will be performed in the absence of arterial wall, and in the presence of intact and damaged blood vessel wall, applying shear stress waveforms obtained from the CFD simulations. The second system is a Left Ventricular Assist Device model with two interchangeable mechanical heart valves.