CHARACTERISTICS OF CORONARY ARTERY CONSTRICTION

冠状动脉收缩的特点

• 批准号: 3082997
• 负责人: Joseph A. Vita
• 金额: $ 8.26万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3082997
• 关键词: acetylcholine; angiography; antiadrenergic agents; arginine; aspirin; bioassay; cholesterol; coronary artery; coronary disorder; coronary occlusion /thrombosis; coronary vasodilator; disease /disorder model; heart catheterization; human subject; lovastatin; miniature swine; nitric oxide; phenylephrine; placebos; ultrasound blood flow measurement; vasomotion; acetylcholine; angiography; antiadrenergic agents; arginine; aspirin; bioassay; cholesterol; coronary artery; coronary disorder; coronary occlusion /thrombosis; coronary vasodilator; disease /disorder model; heart catheterization; human subject; lovastatin; miniature swine; nitric oxide; phenylephrine; placebos; ultrasound blood flow measurement; vasomotion

Recent studies have shown that functional abnormalities of atherosclerotic coronary arteries contribute to the production of myocardial ischemia by producing constriction and/or thrombus formation. It is now clear that the vascular endothelium plays a central role in controlling vascular tone and that atherosclerosis has an adverse effect on endothelial vasodilator function. In the proposed training period, the applicant will test the hypothesis that disturbance of the vasomotor function of the endothelium contributes to the production of coronary artery constriction in response to clinically relevant stimuli and that these disturbances are reversible. The effect of L-arginine (the precursor of endothelium-dependent relexating factor, EDRF) on the response to increased blood flow and infused phenylephrine will be examined in patients with coronary artery disease undergoing cardiac catheterization. Arterial function will be assessed by infusing endothelium-dependent agents and examining diameter responses with quantitative angiography and flow responses with Doppler-flow catheter. A placebo-controlled trial is proposed that will determine whether reduction of serum cholesterol can produce an improvement in coronary vasodilator function in patients. The applicant proposes to further examine these issues in an animal model (cholesterol-fed/balloon-injured miniature swine). The vasomotor responses of the iliac and coronary arteries to increased blood flow and infused catecholamines in atherosclerosis will be studied before and after treatment with L-arginine, mono-methyl arginine, D-arginine, methylene blue and specific adrenergic antagonists. Arterial segments will then be excised for study in the organ chamber, providing an opportunity to correlate these experimental methods and to determine the importance of smooth muscle dysfunction in these responses. The issue of reversibility of functional abnormalities will be studied by examining diameter responses in the same animal during cholesterol feeding and during regression. The period of training will provide an opportunity for the applicant to develop new skills and experience as a clinical investigator in the field of ischemic heart disease. The applicant proposes that these studies will provide insight into pathologic mechanisms and suggest new approaches for management of patients with coronary artery disease.

最近的研究表明，动脉粥样硬化的功能异常 冠状动脉有助于产生心肌缺血 产生收缩和/或血栓形成。 现在很明显 血管内皮在控制血管张力和 动脉粥样硬化对内皮血管扩张剂有不利影响 功能。 在拟议的培训期内，申请人将测试 假设内皮的血管舒缩功能的干扰 有助于产生冠状动脉收缩 对于临床相关的刺激，这些干扰是可逆的。 L-精氨酸的作用（内皮依赖性晶状体的前体 因素，EDRF）关于血流增加并注入的反应 将在冠状动脉疾病患者中检查苯肾上腺素 进行心脏导管插入术。 动脉功能将通过 注入内皮依赖性剂并检查直径反应 多普勒 - 流动导管的定量血管造影和流动响应。 一个 提出了安慰剂对照试验，该试验将确定是否减少 血清胆固醇可以改善冠状动脉血管扩张剂 患者的功能。 申请人建议进一步检查这些 动物模型中的问题（胆固醇喂养/气球受伤的微型 猪）。 叶叶和冠状动脉的血管舒缩反应 血流增加和动脉粥样硬化中注入的儿茶酚胺将是 在用L-精氨酸，单麦甲基精氨酸治疗之前和之后研究 D-精氨酸，亚甲基蓝和特定的肾上腺素能拮抗剂。 动脉 然后，将在器官室中切除细分市场，以提供 将这些实验方法相关联的机会并确定 在这些反应中平滑肌功能障碍的重要性。 问题 功能异常的可逆性将通过检查 胆固醇进食期间和期间，同一动物的直径反应 回归。 培训期将为 作为临床研究者发展新技能和经验的申请人 在缺血性心脏病领域。 申请人建议这些 研究将提供有关病理机制的洞察力，并提出新的 治疗冠状动脉疾病患者的方法。