Prior work at Rice University and elsewhere has demonstrated the extreme importance of the shear field present in flowing systems in promoting platelet reactions. The shear field can modify and activate the platelet directly, in addition to the role of increasing mixing, platelet motion, and collisions. The proposed project is a basic study of platelet reaction rates and mechanisms under controlled conditions. Platelets and platelet aggregates will be subjected to known, controlled levels of shear stress in-vitro by means of a rotational viscometer. By means of optical probes developed in this research program. indices of (1) aggregation, (2) dense granule release, and (3) intracellular calcium ion concentration will be monitored continuously. Studies will be carried out on reactions in the presence of various agents, including arachidonic acid metabolites, are of potential value in increasing our understanding of vascular disorders involving platelets. A population balance mathematical analysis, previously developed in this research program, will be improved and extended and used to analyze the experimental results. Parameters will be derived which are directly related to the state of activation of platelets and aggregates. Analysis of these results will help elucidate the time scales and mechanisms of events of significance in cerebrovascular disease.
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