TREATMENT OF CORONARY ENDOTHELIAL DYSFUNCTION

描述：冠状动脉异常或反常收缩 动脉在心肌缺血发病机制中的作用 稳定性心绞痛和不稳定型心绞痛患者。潜在的 血管张力紊乱与动脉粥样硬化有直接关系 内皮依赖性血管紧张性疾病的发生过程及注意损害 血管扩张。低密度脂蛋白和氧化低密度脂蛋白的升高 显示为损害内皮依赖的松弛，证据来自 动脉粥样硬化的实验模型表明，这种损害可以 通过治疗性降低低密度脂蛋白和可能氧化的低密度脂蛋白而逆转 胆固醇。然而，内皮功能障碍的可逆性已经 没有在临床环境中得到解决。因此，申请者 计划测试治疗降低低密度脂蛋白胆固醇的假设 否则低密度脂蛋白和氧化低密度脂蛋白的结合将逆转 血管异常收缩和改善内皮依赖性血管扩张 动脉粥样硬化患者的冠状动脉。利用一个开放的 标记，前瞻性，随机平行设计，冠脉血管舒缩剂 血管内皮依赖性药物冠脉内输注的反应 血管扩张剂、乙酰胆碱和非内皮依赖性扩张剂， 硝酸甘油，将在基线和12个月后进行比较 治疗：1)洛伐他汀和氯苯乙胺(低密度脂蛋白胆固醇组)，2) 洛伐他汀和普罗布考(低密度脂蛋白和氧化低密度脂蛋白组)，或III)饮食 治疗组(对照组)。血管舒缩反应将通过以下方式评估 这是一种先前得到充分验证的定量血管造影术。 这个项目的目的是将基础生物学知识应用于 临床环境。它从以下角度考察动脉粥样硬化 功能性行为。从这项研究中得出的见解可能对 对未来心肌缺血处理的影响，并可能 导致旨在改善功能而不是 动脉粥样硬化的结构方面，从而避免 随后的临床事件。

DESCRIPTION: Abnormal or paradoxical constriction of the coronary arteries contributes to the pathogenesis of myocardial ischemia in patients with both stable and unstable angina. The underlying disturbance in vascular tone is directly related to the atherosclerotic process and the attending impairment of endothelium-dependent vasodilation. Elevations of and oxidized LDL cholesterol have been shown to impair endothelium-dependent relaxation and evidence from experimental models of atherosclerosis suggests that this impairment can be reversed by therapeutic lowering of LDL and possibly oxidized LDL cholesterol. The reversibility of endothelial dysfunction, however, has not been addressed in the clinical setting. The applicants therefore plan to test the hypothesis that therapeutic lowering of LDL cholesterol or the combination of LDL and oxidized LDL cholesterol will reverse abnormal constriction and improve endothelium-dependent vasodilation in coronary arteries in patients with atherosclerosis. Utilizing an open label, prospective, randomized parallel design, the coronary vasomotor responses to the intracoronary infusions of the endothelium-dependent vasodilator, acetylcholine, and the endothelium-independent dilator, nitroglycerin, will be compared at baseline and after 12 months of therapy with, i) lovastatin and cholestyramine (LDL lowering group), ii) lovastatin and probucol (LDL and oxidized LDL group), or iii) diet therapy (control group). The vasomotor responses will be assessed by a previously well validated quantitative angiographic technique. This project aims to apply knowledge derived from basic biology to the clinical setting. It examines atherosclerosis from the point of view of functional behavior. Insights derived from this study may have important implications for the future management of myocardial ischemia and may lead to new strategies aimed at improving the functional rather than structural aspects of atherosclerotic arteries, thereby avoiding subsequent clinical events.