VASCULAR BASIS FOR THE TREATMENT OF ISCHEMIA

治疗缺血的血管基础

• 批准号: 2750324
• 负责人: Peter Howard Stone
• 金额: $ 48.39万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2750324
• 关键词: antihyperlipoproteinemic agent; atherosclerosis; cardiovascular disorder chemotherapy; cardiovascular disorder prevention; clinical research; coronary artery; electrocardiography; human subject; human therapy evaluation; lovastatin; low density lipoprotein; myocardial ischemia /hypoxia; vascular endothelium; vasomotion

The activity of myocardial ischemia is used to assess risk and manage patients with coronary artery disease. The presence and severity of ischemia raises fundamentally important questions about how to treat this problem and reduce the occurrence of adverse outcomes. Pilot studies are in progress evaluating the effectiveness of standard anti-anginal therapies (drugs and revascularization). however, in patients with coronary atherosclerosis, risk factors such as plasma LDL and oxidized LDL are now known to impair endothelial function leading to loss of vasodilation, abnormal vasoconstriction, a procoagulant surface, and adhesion of inflammatory cells. Clinical research has shown that these dysfunctions are important causes of myocardial ischemia in patients with obstructive coronary artery disease. Therefore, we plan to test the hypothesis that athe aggressive treatment of plasma LDL and oxidized LDL will; (a) result in important improvements in the activity of ischemia in patients with coronary artery disease, and (b) reverse characteristic cell/vessel wall dysfunctions in the arteries of these patients with atherosclerosis. We plan a prospective randomized, double-blind, placebo-controlled, parallel design trial in patients with coronary artery disease, active myocardial ischemia and raised plasma LDL. Ambulatory ECG monitoring and ultrasonic examination of endothelium-dependent vasomotion of the brachial artery will both be used to measure athe activity of ischemia and arterial dysfunction at base-line and after 12 months of therapy with (1) standard diet (Control Group), (ii) standard diet plus lovastatin (LDL lowering strategy), and (iii) standard diet, lovastatin and probucol (LDL and oxidized LDL lowering strategy). Pilot studies and preliminary data are presented in support of this proposal. The goals of this project are to test the value of new therapies aimed at treating the vascular dysfunctions that characterize coronary atherosclerosis in an attempt to control the ischemia that is associated with increased risk of adverse outcomes. If this alternative to the present massive use of standard anti-anginal drugs an revascularization proves effective, it would likely have important implications for strategies aimed at control of adverse events affecting patients with coronary artery disease.

心肌缺血的活动性用于评估风险和管理 冠心病患者。 的存在和严重程度 缺血引起了如何治疗这一根本性的重要问题， 减少不良后果的发生。 试点研究包括 正在评估标准抗心绞痛治疗的有效性 （药物和血管重建）。 然而，在冠心病患者中， 动脉粥样硬化，危险因素，如血浆LDL和氧化LDL，现在 已知其损害内皮功能导致血管舒张丧失， 血管收缩异常，促凝血表面，以及 炎症细胞 临床研究表明，这些功能障碍 是梗阻性心肌缺血的重要原因 冠状动脉疾病 因此，我们计划测试假设， 积极治疗血浆LDL和氧化LDL将;（a）结果 在缺血性脑血管病患者中， 冠状动脉疾病，和（B）逆转特征性细胞/血管壁 这些动脉粥样硬化患者的动脉功能障碍。 我们 计划一项前瞻性随机、双盲、安慰剂对照、平行 在冠状动脉疾病、活动性心肌梗死患者中的设计试验 缺血和血浆LDL升高。 动态心电图监测和超声 肱动脉内皮依赖性血管运动的检查将 两者都可用于测量缺血和动脉功能障碍的血管活性 在基线和治疗12个月后，（1）标准饮食（对照 组），（ii）标准饮食加洛伐他汀（LDL降低策略），和 (iii)标准饮食、洛伐他汀和普罗布考（降低LDL和氧化LDL 策略）。 提出了试点研究和初步数据，以支持 这个提议。 该项目的目标是测试新的 旨在治疗血管功能障碍的治疗方法， 冠状动脉粥样硬化，试图控制缺血， 与不良后果风险增加相关。 如果这个替代方案 目前标准抗心绞痛药物的大量使用 证明是有效的，它可能会有重要的影响， 旨在控制影响患者的不良事件的策略 冠心病