CORONARY STENOSIS, VASOMOTION AND THROMBUS FORMATION

冠状动脉狭窄、血管舒缩和血栓形成

• 批准号: 3350611
• 负责人: WILLIAM P SANTAMORE
• 金额: $ 12.52万
• 依托单位: PRESBYTERIAN MEDICAL CENTER OF PHILA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3350611
• 关键词: angina pectoris; artery stenosis; atherosclerosis; cardiovascular pharmacology; coronary occlusion /thrombosis; dogs; fibrinolytic agents; fibrinolytic therapy; heart circulation; human tissue; myocardial infarction; platelet aggregation; swine; thrombosis; vasoactive agent; vasomotion; vasospasm; ventricular fibrillation

Recent clinical observations on coronary artery spasm have generated renewed interest that vasomotion might be involved in the etiology of angina pectoris and myocardial infarction. At the same time, post myocardial infarction thrombolytic therapy has proven to be very successful: a result which supports the view of an occlusive thrombus within the coronary artery as the cause for myocardial infarction. Rather than viewing coronary vasomotion and thrombus formation as two completely separate entities, this grant proposal presents the hypothesis that in the presence of coronary artery stenosis, coronary vasomotion can critically narrow the stenosis and result in the eventual formation of an occlusive thrombus. This grant proposal will analyze different aspects of this hypothesis. In addition to canine and porcine studies, human coronary arteries will be studied. The first section will examine clinically relevant amplifiers of arterial vasoconstriction, denudation and cholesterol in the presence of an arterial stenosis. This section will determine if this amplified vasoconstriction can cause greater flow decreases at lower concentrations of agonist. Such increased sensitivity could be involved in coronary artery spasm. The second section will examine platelet: accumulation, the precursor of clot formation, in an arterial stenosis. In particular, effects of blood flow velocity and/or percent stenosis and denudation on platelet accumulation will be studied. Continuous monitoring of radioactive Indium-lll will enable quantitative determination of platelet: deposition within the stenosis, while morphological analysis will determine exact stenotic size and flow velocity. Relation between blood flow velocity and efficacy of platelet inhibiting agents will also be studied. Conceivably, increased blood flow velocity through arterial stenoses may reduce the efficacy of these agents. Conversely, relation between flow velocity and platelet stimulating agents will be analyzed. The last section will examine the interaction of platelet accumulation and vasoconstriction. Since most human coronary stenoses are capable of vasomotion, it is imperative to analyze effect of platelet accumulation in a stenosis capable of vasomotion. The information gained in this grant proposal will provide new insight into the pathogenesis of angina pectoris, ventricular fibrillation, myocardial infarction, and cerebral vascular accidents. This new knowledge will be of vital importance to millions of Americans suffering from coronary heart disease and may help to interpret clinical data and shape future therapy.

最近对冠状动脉痉挛的临床观察表明， 引起了新的兴趣，血管舒缩可能参与了 心绞痛和心肌梗死的病因。 在同一 时间，心肌梗死后溶栓治疗已被证明 非常成功：一个支持一个观点的结果 冠状动脉内的闭塞性血栓是导致 心肌梗死 而不是观察冠状动脉血管运动， 血栓形成作为两个完全独立的实体，这项赠款 该提案提出了一个假设，即在存在冠状动脉病变的情况下， 动脉狭窄，冠状动脉血管运动可以严重缩小 狭窄并导致最终形成闭塞 血栓 这份拨款提案将分析不同方面的 这个假设。 除了犬和猪的研究外， 将研究冠状动脉。 第一部分将审查 临床相关的动脉血管收缩放大器， 剥脱和胆固醇在动脉狭窄的存在。 本节将确定这种放大的血管收缩是否可以 在较低浓度的激动剂下导致更大的流量下降。 这种敏感性的增加可能涉及冠状动脉 痉挛 第二部分将检查血小板：积聚， 动脉狭窄时血栓形成的前兆 在 特别是血流速度和/或狭窄百分比的影响 和剥脱对血小板聚集的影响。 对放射性铟III的持续监测将使 血小板的定量测定： 狭窄，而形态学分析将确定确切的 狭窄大小和流速。 血流量之间的关系 血小板抑制剂的速度和功效也将被 研究了 可以想象，增加血液流速通过 动脉狭窄可能降低这些药物的疗效。 相反，流速和血小板刺激之间的关系 将对代理人进行分析。 最后一节将研究 血小板聚集和血管收缩相互作用。 以来 大多数人的冠状动脉狭窄能够血管舒缩， 必须分析血小板聚集在狭窄中作用 有血管舒缩的能力 在这次赠款中获得的信息 该提案将为心绞痛的发病机制提供新的见解 心绞痛、室颤、心肌梗死和 脑血管意外 这些新知识将是至关重要的 对数百万患有冠心病的美国人来说， 可能有助于解释临床数据和塑造未来 疗法