Mathematical Sciences: Mathematical Modeling and Computational Simulation of Platelet Aggregation in Large and Small Vessels

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9307643 Fogelson The investigator extends earlier analytical and computational work on a microscopic-scale model of aggregation of blood platelets in small diameter blood vessels, and on a continuum model of aggregation in large diameter vessels. Both models involve interactions between the blood's fluid dynamics and the mechanics and chemistry of developing aggregates. For the microscopic-scale model, the project involves: 1) completing the development of the numerical tools needed to extend simulations to three dimensions; 2) exploring and implementing strategies for performing computationally intensive three-dimensional calculations on high-performance parallel computers; 3) constructing a computational analogue of the experimental flow chamber of his collaborator J. Hubbell (Chemical Engineering, University of Texas) and comparing simulations with it to Hubbell's data on the dynamics of aggregate growth; 4) modifying aspects of the model that concern a platelet's response to pro-aggregating agents and the efficiency of platelet-platelet cohesion; and 5) exploring the range of behavior of the model and its sensitivity to parameter variations. For the continuum model, the project requires: 1) developing numerical methods to study forms of the model that allow strain-dependent aggregate breakup; 2) developing techniques for incorporating into this model platelet interactions with the blood vessel's wall or the reactive surface of a prosthetic cardiac valve; and 3) studying the behavior of the model when aggregation is initiated by exogenous stimuli in bulk flow, or by contact with a reactive wall of a coronary-artery-sized vessel. In the latter context, it is of particular interest to study how the interaction between flow and vessel geometry affects aggregate formation. Platelet aggregates form on blood vessel walls in response to vascular injury; they are also major constituents of the life-threatening blood clots associated with vascular diseas e and with the use of cardiovascular prostheses. The modeling and simulations carried out in this project complement traditional laboratory experimentation. They provide detailed information, of a type that is generally not attainable in the laboratory, about the dynamic interactions among the components of the aggregation response. This additional information will increase our insight into the physical and chemical controls on the aggregation process. These studies also lay the foundations for further development of aggregation models and for their application to clinically interesting questions, including how flow and vessel geometry interact to influence aggregation within natural vessels, such as the coronary arteries, or prosthetic devices, such as vascular grafts or artificial hearts. The numerical tools developed in this project should also be valuable in solving a broad range of biofluid dynamics and engineering problems. ***