REVASCULARIZATION OF ACUTE MYOCARDIAL INFARCTION

急性心肌梗塞的血运重建

• 批准号: 3351344
• 负责人: Jakob VINTEN-JOHANSEN
• 金额: $ 25.11万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3351344
• 关键词: acute disease /disorder; coronary occlusion /thrombosis; disease /disorder model; dogs; free radicals; heart disorder diagnosis; heart function; heart metabolism; heart revascularization; hydroxyl group; myocardial infarct sizing; myocardial infarction; myocardial ischemia /hypoxia; particle; radionuclide diagnosis; ultrasound blood flow measurement

The current understanding of myocardial ischemia emphasizes that the degree of damage is related to the duration and severity of coronary occlusion. Consequently, therapeutic management has been directed toward limiting ischemic damage by reducing the duration and severity of oxygen supply and demand disparity. We hypothesize that the total damage following coronary occlusion is caused by alterations set up during ischemia but then further extended during reperfusion. This hypothesis suggests that reperfusion injury can be avoided by modifying the reperfusion phase. Surgical revascularization of acute evolving myocardial infarction using cardioplegia allows control of the composition of the initial reperfusate as well as the conditions of its delivery. When delivered into the ischemic segment, cardioplegia is the first reperfusate to which that segment is exposed. Control of reperfusion can avoid this reperfusion injury to a large extent. Such control of reperfusion is not possible with nonsurgical revascularization using thrombolysis and/or angioplasty. Although well tested in global models, the role of surgical revascularization of acute evolving myocardial infarction remains unclear. The studies outlined in the following application will demonstrate that the fate of the ischemic myocardium is related not only to the ischemic phase, but is in large part determined by events occurring during reperfusion. In a canine model of 1, 3 and 6 hour left anterior descending coronary artery occlusions, we will a) determine the functional, metabolic , and morphological characteristics of ischemic and reperfusion injury, b) determine the pathophysiological mechanisms underlying "stunned" myocardium and describe stunning as as manifestation of reperfusion injury, c) provide insight on the failure of nonsurgical revascularization to restore postischemic function, d) show that reperfusion injury can be avoided by modifying the conditions and composition of reperfusion with surgical revascularization using cardioplegia, resulting in immediate restoration of postischemic function and metabolism, e) determine the optimal cardioplegia for the setting of evolving infarction, f) determine the long-tem benefits of surgical versus nonsurgical revascularization in chronic studies, g) and examine the benefits of retrograde coronary sinus cardioplegia over antegrade delivery.

当前对心肌缺血的理解强调 损害程度与持续时间和严重程度有关 冠状动脉阻塞。 因此，治疗管理 通过减少来指向限制缺血损伤 氧供应和需求差异的持续时间和严重程度。 我们假设冠状动脉后的总损害 闭塞是由缺血期间建立的改变引起的，但 再灌注期间进一步扩展。 该假设表明 可以通过修改来避免再灌注损伤 再灌注阶段。 急性进化的手术血运重建 使用心脏杂志的心肌梗塞可以控制 初始再生和条件的组成 它的交付。 当输送到缺血细分市场时 Cardioplegia是该细分市场的第一个记者 裸露。 控制再灌注可以避免这种再灌注损伤 在很大程度上。 这种对再灌注的控制是不可能的 使用溶栓和/或的非外科血运重建 血管成形术。 尽管在全球模型中经过了良好的测试，但 急性进化心肌梗塞的手术血运重建 仍然不清楚。 以下应用中概述的研究 将证明缺血性心肌的命运是 不仅与缺血阶段有关，而且很大程度上是 取决于再灌注期间发生的事件。 在犬类中 1、3和6小时左下冠状动脉的模型 闭塞，我们将a）确定功能，代谢和 缺血和再灌注损伤的形态学特征， b）确定基础的病理生理机制 “震惊”心肌，并将惊人的表现形容为 再灌注损伤，c）提供有关失败的见解 非手术血运重建以恢复缺血后功能，d） 证明可以通过修改可以避免再灌注损伤 通过手术的疾病和再灌注的组成 使用心脏杂志的血运重建，立即导致 恢复缺血后功能和代谢，E） 确定开发的最佳心脏病 梗塞，f）确定手术与 慢性研究中的非手术血运重建，g）并检查 逆行冠状动脉鼻子肠的好处 流过的交付。