PLATELET REACTIONS UNDER CONTROLLED FLUID SHEAR STRESS

研究的总体目标是提高我们对 血小板事件的反应动力学和机制 心血管疾病我们将血液样本进行已知的，受控的 水平的剪切应力在旋转粘度计和确定 通过使用流式细胞术方法检测反应。这些研究报告将 在不存在添加剂和存在血小板的情况下进行 激动剂和拮抗剂。部分工作旨在改善和扩大我们的 用于研究血小板活化的流式细胞术方法， 聚集在全血中，并通过 人口平衡数学模型，以确定碰撞 效率和破碎率参数作为生化 环境、剪切速率和剪切暴露时间。同时，我们将 使用两种血栓形成模型进行研究， Ohshima和他在筑波大学的同事说。两种型号都使用 一种刺激血栓形成的荧光染料光方法， 测量血小板血栓形成和生长速率，并允许 流体机械剪切应力的定量评估和控制。 一种模型将培养的内皮细胞单层结合在锥状细胞中， 板式旋转粘度计粘度计应用已知的受控的 与内皮细胞接触的血小板悬液的剪切应力 细胞单层第二个模型测量血栓形成和血栓形成的速率。 血栓生长的大鼠血管通过使用一个活体 显微镜电视系统

The overall goal of the research is to improve our understanding of reaction kinetics and mechanisms of platelet events of significance in cardiovascular disorders. We subject blood specimens to known, controlled levels of shear stress in a rotational viscometer and determine the response by use of the flow cytometric methods. These studies will be done both in the absence of added agents, and in the presence of platelet agonists and antagonists. Part of the work aims to improve and extend our flow cytometric methodology for studying platelet activation and aggregation in whole blood, and to analyze the results by means of a population balance mathematical model to determine the collision efficiency and breakage rate parameters as functions of biochemical environment, shear rate and shear exposure time. In parallel we will carry out studies using two thrombogenesis models developed by Dr. Ohshima and his colleagues at the University of Tsukuba. Both models use a fluorescent dye-light method of stimulation of thrombus formation, measure platelet thrombus initiation and growth rate, and allow quantitative assessment and control of fluid mechanical shear stress. One model incorporates a cultured endothelial cell monolayer in a cone- plate rotational viscometer. The viscometer applies a known, controlled shear stress to a platelet suspension in contact with the endothelial cell monolayer. A second model measures thrombus initiation and the rate of thrombus growth in blood vessels of rats by use of an intravital microscope-television system.