MECHANISMS OF OCCLUSION IN A STENOSED CORONARY ARTERY

狭窄冠状动脉的闭塞机制

• 批准号: 3356890
• 负责人: CLAUDE R BENEDICT
• 金额: $ 17.38万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3356890
• 关键词: adenosine diphosphate; aminophylline; arachidonate; artery occlusion; artery stenosis; aspirin; calcium; catechol methyltransferase; coronary artery; coronary occlusion /thrombosis; crystallization; diltiazem; dogs; eicosanoid metabolism; electrocardiography; enzyme inhibitors; epinephrine; ergolines; gel filtration chromatography; heart catheterization; heart circulation; hemodynamics; heparin; high performance liquid chromatography; histamine; hydrazines; imidazole; isomerase; myocardial infarction; platelet aggregation; platelet aggregation inhibitors; prostacyclins; prostaglandin E; prostaglandin analogs; prostaglandin endoperoxide synthase; scanning electron microscopy; serotonin; serotonin inhibitor; thromboxanes; ultrasound blood flow measurement; vascular resistance; vasoconstriction; vasomotion

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.

最近的研究表明，血栓形成的重要性， 冠状动脉闭塞和心肌梗死。 但 血栓形成和导致冠状动脉闭塞的潜在机制 仍然没有解决。 大多数关于血栓的研究 已经在体外系统中进行了形成。 主 本研究的目的是确定血小板聚集的作用 在体内冠状动脉闭塞中的血管收缩 自发性冠状动脉血栓形成模型。 血清素释放 在血小板聚集期间，将被用作 血小板聚集 会形成部分冠状动脉血栓 在狗的动脉腔中施加D/C电流。 后 电流停止，血栓自发延伸至闭塞 动脉 血小板聚集将通过以下指标的变化进行评估： 通过冠状窦导管抽取血浆5-羟色胺水平。 将通过灵敏的放射酶法测定血清素。 体内血管反应性（血管舒缩）将通过 缝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，长度节段晶体（左心室 收缩力）、Millar导管（血压）和心外膜 心电图。 选择的药物（阿司匹林，LY 53857，达唑昔苯， 氨茶碱、PGE 1、SQ 29548、肝素、地尔硫卓） 单独或组合地抑制特定的机制， 血小板聚集和血管收缩。 输注研究 与肾上腺素、血清素或组织胺的混合会评估 在局部血管对autocoids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，与初始事件无关 血栓形成 该实验室的初步研究 证明了这些实验在体内的可行性 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 冠状动脉血流和心肌血流的动态测量 功能