TREATMENT OF CORONARY ENDOTHELIAL DYSFUNCTION

冠状动脉内皮功能障碍的治疗

• 批准号: 2226096
• 负责人: ANDREW Peter SELWYN
• 金额: $ 18.8万
• 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 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226096
• 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：冠状动脉的异常或矛盾的收缩 动脉有助于心肌缺血的发病机理 稳定和不稳定心绞痛的患者。 基础 血管张力的干扰与动脉粥样硬化直接相关 过程和依赖内皮的障碍 血管舒张。 升高和氧化的LDL胆固醇已经 证明会损害内皮依赖性放松和证据 动脉粥样硬化的实验模型表明，这种障碍可以 通过降低LDL的治疗性和可能氧化的LDL可以逆转 胆固醇。 但是，内皮功能障碍的可逆性已有 在临床环境中没有解决。 因此，申请人 计划测试LDL胆固醇治疗性降低的假设 或LDL和氧化的LDL胆固醇的组合将逆转 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 标签，前瞻性，随机平行设计，冠状动脉舒适器 对内皮依赖性冠状体输注的反应 血管扩张剂，乙酰胆碱和内皮无关的扩张仪， 硝酸甘油，将在基线和12个月后进行比较 i）lovastatin和cholestyramine（LDL降低组），ii），ii） lovastatin和progucol（LDL和氧化的LDL组）或iii）饮食 治疗（对照组）。 血管舒缩响应将由 先前经过良好验证的定量血管造影技术。 该项目旨在将基本生物学衍生的知识应用于 临床环境。 它从 功能行为。 从这项研究中得出的见解可能具有重要的 对心肌缺血的未来管理的影响 导致旨在改善功能而不是的新策略 动脉粥样硬化动脉的结构方面，从而避免 随后的临床事件。