MECHANISMS OF ALTERED CORONARY BLOOD FLOW

冠状动脉闭塞和心肌梗死的机制 梗死仍未消退。 已经使用各种机械装置来 在动物模型中产生部分或完全血管闭塞， 心肌缺血 这些研究提供了重要信息 与缺血相关的病理生理事件，但没有 探讨了血栓形成本身在缺血性心脏病演变中的作用， 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。 本研究的主要目的是 确定血小板聚集在冠状动脉粥样硬化中的作用 在体内缺血模型中的动脉闭塞， 接近临床情况。 在血小板聚集过程中， 血清素被释放到血浆中。 这一增长可以作为 血小板聚集指数，如果释放的5-羟色胺的再积聚 受到完整血小板的抑制。 各种药物干预 将被用于选择性地抑制特定的途径， 血小板聚集和血栓形成。 本研究的主要目的 涉及血小板聚集作为主要贡献者的作用 血栓扩展导致冠状动脉完全闭塞。 一 部分冠状动脉血栓将在器械犬中形成， 向动脉内腔施加电流。 体内血小板 聚集将通过获得的血浆5-羟色胺水平的变化来评估 通过冠状窦导管 血浆血清素浓度将 通过灵敏的放射酶法测定。 相关测量 将使用多普勒血流探头， 长度节段测量仪（左心室收缩力），Millar压力 导管（血压）和心外膜ECG。 选择的药物（阿司匹林， 酮色林、达唑昔本、地尔硫卓、氨茶碱）将单独使用或 阻断与血小板相关的特定机制的组合 聚合来 这些实验的目的是为了获得一个更好的 了解血小板在自发性延长 现有血栓导致冠状动脉闭塞，而不是初始事件 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，可以定量评估 血小板聚集和血栓形成的同时， 冠状动脉血流量和心肌功能的测量。

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.