MECHANISMS OF ALTERED CORONARY BLOOD FLOW

冠状动脉闭塞与心肌梗死的机制 梗塞仍未解决。已经使用了各种机械手段来 建立部分或完全血管闭塞的动物模型 心肌缺血。这些研究提供了重要的信息 与缺血相关的病理生理事件，但没有 探讨血栓形成本身在脑缺血演变中的作用 心脏病。大多数关于血栓形成的研究都是 在体外系统中进行。这项研究的主要目标是 确定血小板聚集在冠状动脉病变中的作用 动脉闭塞在体内的缺血模型中更接近 与临床情况接近。在血小板聚集过程中， 5-羟色胺释放到血浆中。这一增长可以被用作 血小板聚集指数，如果释放的5-羟色胺重新积聚 被完整的血小板抑制。各种药理干预措施 将被用来选择性地抑制参与的特定通路 血小板聚集和血栓形成。这项研究的主要目的 是针对作为主要贡献者的血小板聚集的作用 血栓延伸导致冠状动脉完全闭塞。一个 通过以下方法在仪表犬体内形成部分冠状动脉血栓 将电流应用于动脉腔内。体内血小板 聚集性将通过获得的血浆5-羟色胺水平的变化来评估 通过冠状静脉窦导管。血浆5-羟色胺浓度将是 用一种灵敏的放射酶方法测定。相关测量 将使用多普勒血流探头进行心肌功能的检测， 长度节段测量器(左心室收缩能力)、毫升压 导管(血压)和心外膜心电图。选定的药物(阿司匹林、 酮色林、达唑西班、地尔硫卓、氨茶碱)将单独使用或在 联合用药阻断与血小板相关的特定机制 聚合。这些实验的主旨是为了获得更好的 了解血小板在自发延长血管内皮细胞生长中的作用 现有血栓导致冠状动脉闭塞，而不是最初的事件 与血栓形成有关。本实验室的初步研究 已经清楚地证明了实现这些目标的可行性 在体内模型中的实验可以定量地评估两者 动态同时进行的血小板聚集和血栓形成 测量冠脉血流量和心肌功能。

The mechanisms contributing to coronary artery occlusion and myocardial infarction remain unresolved. Various mechanical means have been used to produce partial or complete vascular occlusion in animal models of myocardial ischemia. These studies have provided significant information on the patho-physiological events associated with ischemia, but have not explored the role of thrombus formation per se in the evolution of ischemic heart disease. The majority of studies on thrombus formation have been conducted in in vitro systems. The primary goal of this study is to determine the role of platelet aggregation in contributing to coronary artery occlusion in an in vivo model of ischemia that more closely approximates the clinical situation. During platelet aggregation, serotonin is released into the plasma. This increase can be used as an index of platelet aggregation, if the reaccumulation of released serotonin by intact platelets is inhibited. Various pharmacological interventions will be utilized to selectively inhibit specific pathways involved in platelet aggregation and thrombus formation. The major aims of this study are directed to the role of platelet aggregation as a primary contributor to thrombus extension resulting in complete coronary artery occlusion. A partial coronary thrombus will be formed in instrumented dogs by application of current to the intraarterial lumen. In vivo platelet aggregation will be assessed by changes in plasma serotonin levels obtained via coronary sinus catheters. Plasma serotonin concentrations will be determined by a sensitive radioenzymatic method. Correlative measurements of myocardial function will be made using Doppler flow probes, length-segment gauges (left ventricular contractility), Millar pressure catheters (blood pressure) and epicardial ECGs. Selected agents (aspirin, Ketanserin, dazoxiben, diltiazem, aminophylline) will be used singly or in combination to block specific mechanisms associated with platelet aggregation. The thrust of these experiments is to gain a better understanding of the role of platelets in spontaneously extending an existing thrombus leading to coronary occlusion, not to the initial events associated with thrombogenesis. Preliminary studies in this laboratory have clearly demonstrated the feasibility of accomplishing these experiments in an in vivo model that can quantitatively assess both platelet aggregation and thrombus formation simultaneously with dynamic measurements of coronary blood flow and myocardial function.