TREATMENT OF CORONARY ENDOTHELIAL DYSFUNCTION

冠状动脉内皮功能障碍的治疗

• 批准号: 2378791
• 负责人: ANDREW Peter SELWYN
• 金额: $ 13.12万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2378791
• 关键词: acetylcholine; angiography; antihypercholesterolemic agent; atherosclerosis; cardiovascular pharmacology; cholesterol; cholestyramine; coronary disorder; diet therapy; drug screening /evaluation; heart disorder chemotherapy; human subject; human therapy evaluation; lovastatin; low density lipoprotein; nitroglycerin; oxidized lipid; ultrasound blood flow measurement; vasodilators; vasomotion

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.

描述：冠状动脉异常或矛盾收缩 动脉有助于心肌缺血的发病机制 患有稳定型和不稳定型心绞痛的患者。 底层的 血管张力的紊乱与动脉粥样硬化直接相关 内皮依赖性的过程和伴随的损伤 血管舒张。 LDL 胆固醇升高并被氧化 显示会损害内皮依赖性松弛，证据来自 动脉粥样硬化的实验模型表明，这种损伤可以 可通过治疗性降低 LDL 和可能氧化的 LDL 来逆转 胆固醇。 然而，内皮功能障碍的可逆性 临床环境中尚未得到解决。 申请人因此 计划检验治疗性降低 LDL 胆固醇的假设 或者低密度脂蛋白和氧化低密度脂蛋白胆固醇的结合会逆转 异常收缩并改善内皮依赖性血管舒张 动脉粥样硬化患者的冠状动脉。 利用开放式 标签、前瞻性、随机平行设计、冠状血管舒缩 内皮依赖性冠状动脉内输注的反应 血管扩张剂、乙酰胆碱和内皮依赖性扩张剂， 硝酸甘油，将在基线时和 12 个月后进行比较 治疗，i) 洛伐他汀和考来烯胺（LDL 降低组），ii) 洛伐他汀和普罗布考（LDL 和氧化 LDL 组），或 iii) 饮食 治疗（对照组）。 血管舒缩反应将通过以下方式评估 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 临床环境。 它从以下角度检查动脉粥样硬化： 功能行为。 这项研究得出的见解可能具有重要意义 对未来心肌缺血治疗的影响 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。