MECHANISMS OF OCCLUSION IN A STENOSED CORONARY ARTERY

最近的研究表明血栓形成在心脏疾病中的重要性 冠状动脉闭塞和心肌梗死。然而， 血栓形成和导致冠状动脉闭塞的机制 仍然悬而未决。大多数关于血栓的研究 已经在体外系统中进行了形成。初级阶段 这项研究的目的是确定血小板聚集的作用 在体冠状动脉闭塞时的血管收缩 自发性冠状动脉血栓形成模型。5-羟色胺释放 在血小板聚集过程中将被用作体内指标 血小板聚集。会形成部分冠状动脉血栓 在狗的动脉管腔上施加D/C电流。之后 电流停止，血栓自发延伸至闭塞 动脉。将通过以下变化来评估血小板聚集： 经冠状静脉窦导管采集血浆5-羟色胺水平。 5-羟色胺将用一种灵敏的放射酶方法测定。 体内血管反应性(血管运动)将通过以下方法测量 缝合在动脉壁上的微晶体。相关 将使用多普勒测量心肌功能 流量探头，长度段晶体(左心室 收缩能力)、米勒导管(血压)和心外膜 心电信号。选定的药物(阿司匹林、LY53857、达唑西本、 将使用氨茶碱、前列腺素E_1、SQ29548、肝素、地尔硫) 单独或联合使用，以抑制导致 与血小板聚集和血管收缩有关。输液研究 使用肾上腺素、5-羟色胺或组胺可以评估这种变化。 在局部血管对自体皮质激素的反应中 血栓形成。这些实验的主旨是为了更好地 了解血小板和血管反应性在 闭塞性冠状动脉血栓形成，与最初的相关事件无关 血栓形成。这个实验室的初步研究已经 证明了这些实验在活体内的可行性 可以定量评估血小板聚集的模型， 血栓形成和血管反应性同时发生 冠脉血流和心肌的动态测量 功能。

Recent studies demonstrate the importance of thrombosis in coronary occlusion and myocardial infarction. However, the mechanism underlying thrombosis and resulting coronary occlusion remain unresolved. 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 and vasoconstriction in coronary artery occlusion in an in vivo model of spontaneous coronary thrombosis. Serotonin release during platelet aggregation will be used as an in vivo index of platelet aggregation. A partial coronary thrombus will be formed in dogs by application of D/C current to the arterial lumen. After the current is stopped, thrombus spontaneously extends to occlude the artery. Platelet aggregation will be assessed by changes in plasma serotonin levels drawn via coronary sinus catheter. Serotonin will be assayed by a sensitive radioenzymatic method. In vivo vascular reactivity (vasomotion) will be measured by microcrystals sewn to the arterial wall. Correlative measurements of myocardial function will be made using Doppler flow probes, length segment crystals (left ventricular contractility), Millar catheters (blood pressure), and epicardial ECGs. Selected agents (aspirin, LY53857, dazoxiben, aminophylline, PGE1, SQ29548, heparin, diltiazem) will be used singly or in combination to inhibit specific mechanisms that lead to platelet aggregation and vasoconstriction. Infusion studies with epinephrine, serotonin or histamine will assess the alteration in local vascular response to autocoids that may be present during thrombus formation. The thrust of these experiments is to better understand the role of platelets and vascular reactivity in occlusive coronary thrombosis, not to the initial events associated the thrombogenesis. Preliminary studies in this laboratory have demonstrated the feasibility of these experiments in an in vivo model that can quantitatively assess platelet aggregation, thrombus formation, and vascular reactivity simultaneously with dynamic measurements of coronary of blood flow and myocardial function.