CHARACTERISTICS OF CORONARY ARTERY CONSTRICTION

最近的研究表明，动脉粥样硬化的功能异常 冠状动脉有助于心肌缺血的产生， 产生收缩和/或血栓形成。 现在很清楚， 血管内皮在控制血管张力方面发挥着核心作用， 动脉粥样硬化对内皮血管扩张剂有不利影响 功能 在建议的培训期内，申请人须测试 血管内皮功能紊乱假说 导致冠状动脉收缩 临床相关刺激，这些干扰是可逆的。 血管内皮依赖性舒张反应的前体--L-精氨酸对内皮细胞增殖的影响 因子，EDRF）对增加血流量和输注 将在患有冠状动脉疾病的患者中检查苯丙氨酸 接受心导管插入术 将通过以下方式评估动脉功能： 输注内皮依赖性药物并检查直径反应， 多普勒血流导管定量血管造影和血流反应。 一 建议进行一项安慰剂对照试验，以确定是否减少 血清胆固醇水平的降低可以改善冠状动脉血管舒张功能 在患者中发挥作用。 申请人建议进一步审查这些 动物模型中的问题（胆固醇喂养/球囊损伤的微型 猪）。 髂动脉和冠状动脉的血管反应 动脉粥样硬化中增加的血流量和注入的儿茶酚胺将是 在用L-精氨酸，单甲基精氨酸， 精氨酸、亚甲蓝和特异性肾上腺素能拮抗剂。 动脉 然后将切除节段用于器官室中的研究，提供 有机会关联这些实验方法，并确定 平滑肌功能障碍在这些反应中的重要性。 问题 将通过检查来研究功能异常的可逆性 在胆固醇喂养期间和在 回归分析 培训期间将提供机会， 申请人作为临床研究者发展新的技能和经验 在缺血性心脏病领域。 申请人建议，这些 研究将提供对病理机制的深入了解，并提出新的 冠状动脉疾病患者的管理方法。

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.