PLATELET AND MICROVASCULAR RESPONSES

该提案是HL 23560的延续和重大扩展， 糖尿病小鼠血小板聚集。 我们将继续研究血小板 糖尿病患者血管性脑损伤后脑微血管的聚集 损伤 我们现在将扩展我们的研究，包括分析 血管直径发生损伤后，血管的变化 未受伤船只的反应。 对损伤的反应，即血小板 糖尿病患者的聚集和直径改变，将与 糖尿病患者的血管反应性也是如此。 此外，我们在 扩大了体内研究， 与肠系膜微血管反应相比。 研究将 在幼年和成年糖尿病发作的动物中进行 而不是像以前那样混合在一起。 体内聚集将是 与在线测定的红细胞速度值（剪切速率）相关， “标准化”以考虑速度的差异。 研究 血浆脂质组分、胰岛素水平和血小板胰岛素受体 增加了前列腺素水平和合成的研究。 是 希望从后面的研究中获得的信息将相互关联 和/或解释体内观察结果。 为了进一步解释 体内数据，广泛的体外聚集研究，使用血小板 富血浆和洗涤的血小板已被添加到方案中。 这些 体外研究还将包括血小板释放的研究 与非糖尿病患者相比，

This proposal represents a continuation and major expansion of HL 23560, Platelet Aggregation in Diabetic Mice. We will continue to study platelet aggregation in cerebral microvessels of diabetics following vascular injury. We will now extend our study to include analysis of changes in vessel diameter that occur after injury and to changes in vascular reactivity of uninjured vessels. The response to injury, that is platelet aggregation and altered diameter in diabetics, will be compared with that in normals, as will vascular reactivity in diabetics. In addition our in vivo studies are expanded so that cerebrovascular responses will be compared with microvascular responses in mesentery. Studies will be carried out both in animals with juvenile and adult onset of diabetes rather than with a mixed group as before. In vivo aggregaton will be related to red cell velocity values (shear rates) determined on-line and "normalized" to take differences in velocity into account. Studies of plasma lipid fractions, insulin levels and the platelet insulin receptor are added as are studies of prostaglandin levels and synthesis. It is hoped that the information obtained from the latter studies will correlated with and/or explain in vivo observations. In a further effort to explain in vivo data, extensive in vitro studies of aggregation, using platelet rich plasma and washed platelets, have been added to the protocol. These in vitro studies will also include investigations of the platelet release reaction in diabeties compared with non diagetics.