TREATMENT OF CORONARY ENDOTHELIAL DYSFUNCTION

冠状动脉异常或反常收缩 动脉有助于心肌缺血的发病机制， 稳定型和不稳定型心绞痛患者。 底层 血管张力紊乱与动脉粥样硬化直接相关， 内皮依赖性血管紧张素Ⅱ的过程及其伴随的损伤 血管舒张 氧化低密度脂蛋白胆固醇的升高 显示损害内皮依赖性舒张，证据来自 动脉粥样硬化的实验模型表明， 通过治疗性降低LDL和可能的氧化LDL来逆转 胆固醇 然而，内皮功能障碍的可逆性， 尚未在临床环境中得到解决。 因此，申请人 计划检验治疗性降低低密度脂蛋白胆固醇 或者LDL和氧化LDL胆固醇的结合会逆转 异常收缩和改善内皮依赖性血管舒张， 动脉粥样硬化患者的冠状动脉。 利用开放的 标签，前瞻性，随机平行设计，冠状动脉血管造影 对冠状动脉内输注内皮依赖性 血管扩张剂乙酰胆碱和非内皮依赖性扩张剂， 将在基线和12个月后进行比较， 用i）洛伐他汀和消胆胺（LDL降低组）治疗，ii） 洛伐他汀和普罗布考（LDL和氧化LDL组），或iii）饮食 治疗组（对照组）。 将通过以下方式评估血管反应： 这是一种先前经过充分验证的定量血管造影技术。 该项目旨在将基础生物学知识应用于 临床设置。 它从以下角度研究动脉粥样硬化： 功能性行为 从这项研究中得出的见解可能具有重要意义 对未来心肌缺血管理的影响， 导致新的战略，旨在改善功能，而不是 动脉粥样硬化动脉的结构方面，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.