CORONARY ARTERY CONSTRICTION

最近的研究表明，动脉粥样硬化的功能异常 冠状动脉通过以下途径促进心肌缺血的产生 产生收缩和/或血栓形成。现在很明显， 血管内皮细胞在控制血管张力和 动脉粥样硬化对内皮血管扩张剂有不利影响 功能。在建议的培训期间，申请者将测试 假设血管内皮的血管运动功能紊乱 导致冠状动脉收缩反应的产生 与临床相关的刺激，这些干扰是可逆的。 血管内皮细胞依赖性松弛的前体L-精氨酸的作用 因子，EDRF)对增加的血流和输注的反应 冠心病患者将接受苯肾上腺素检查 正在接受心脏导管术的。动脉功能将通过以下方式评估 输注内皮依赖性药物并检测直径反应 多普勒血流导管的定量血管造影和血流反应。一个 建议进行安慰剂对照试验，以确定是否减少 降低血清胆固醇可以改善冠状动脉血管扩张剂 在病人身上起作用。申请人建议进一步研究这些问题 动物模型中的问题(胆固醇喂养/气球损伤的微型模型 猪)。大鼠髂动脉和冠状动脉的血管运动反应 动脉粥样硬化的血流量增加和儿茶酚胺输注将是 观察L-精氨酸、单甲基精氨酸、 D-精氨酸、亚甲蓝和特定的肾上腺素能拮抗剂。动脉 然后，节段将被切除以在器官室内进行研究，提供 有机会将这些实验方法联系起来并确定 在这些反应中，平滑肌功能障碍的重要性。这一问题 功能异常的可逆性将通过检查 同一动物在喂饲胆固醇期间和在 回归。培训期间将为以下人员提供机会 申请者作为临床调查员发展新技能和经验 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洞察并提出新的 冠状动脉疾病患者的治疗方法。

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.