POSITRON TOMOGRAPHY IN ISCHEMIC HEART DISEASE

正电子断层扫描在缺血性心脏病中的应用

• 批准号: 2028170
• 负责人: HEINRICH R SCHELBERT
• 金额: $ 55.09万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2028170
• 关键词: angiography; cardiovascular disorder prevention; coronary disorder; coronary vasodilator; diet therapy; dietary lipid; dipyridamole; early diagnosis; estrogens; exercise; female; heart circulation; heart imaging /visualization /scanning; heart metabolism; hormone therapy; human subject; lifestyle; myocardial ischemia /hypoxia; noninvasive diagnosis; positron emission tomography; postmenopause; radionuclides; reactive hyperemia; smoking cessation; vasomotion

Quantitative, dynamic imaging with Positron Emission Tomography (PET) of N-13 ammonia, C-11 acetate and F-18 deoxyglucose during the past funding period afforded the quantification of regional myocardial blood flow (MBF) and of substrate metabolism in patients early after a myocardial infarction or with chronic coronary artery disease (CAD). Our accomplishments provide further support for the clinical relevance of cardiac PET imaging of MBF and metabolism and offer new insights into the pathophysiology of myocardial ischemia. We believe that additional mechanistic information can be gained only under more controlled conditions in the animal laboratory. Therefore, we wish to refocus the proposed research on the noninvasive assessment of altered vasomotion early in the evolution of CAD as well as in clinically manifest CAD. The hypothesis to be tested is that abnormal coronary vasomotion in preclinical and in clinical CAD can be demonstrated noninvasively with MBF measurements by N-13 ammonia and PET and that beneficial effects of dietary, lifestyle and pharmacologic interventions can be demonstrated noninvasively. We will test our hypothesis by addressing four specific questions: (l) Does short term cardiovascular conditioning improve myocardial flow reserve and vasodilator capacity in CAD patients and what factors are responsible for such improvement? (2) Can preclinical CAD be identified by stress interventions? (3) Can abnormal coronary vasomotion be identified in chronic smokers; is it accentuated in CAD but ameliorated by smoking cessation? (4) Does acute and chronic estrogen administration in postmenopausal women with or at risk for CAD improve abnormal vasomotion and protect against CAD? We will address these questions through accurate and reproducible measurements of regional MBF with N-13 ammonia, dynamic PET and a previously validated tracer kinetic model at rest, during pharmacologically induced hyperemia and stress provocation in normal volunteers, patients with preclinical and overt CAD and postmenopausal women. Serial measurements of MBF during these interventions will be performed prior to and after cardiovascular conditioning, smoking cessation and during chronic estrogen replacement We anticipate that accomplishments of the research objectives will provide a noninvasive tool for the detection of early, preclinical CAD, for demonstrating directly the efficacy of widely advocated interventions as for example regular exercise, lipid lowering diet, lifestyle changes and smoking cessation for delaying or reversing progression of the CAD or even prevention and the protective cardiovascular effects of estrogen replacement in postmenopausal women at risk for CAD.

正电子发射断层扫描（PET）定量动态成像， 过去供资期间的N-13氨、C-11乙酸盐和F-18脱氧葡萄糖 期间提供了定量的局部心肌血流量（MBF） 心肌梗死后早期患者的底物代谢 心肌梗死或慢性冠状动脉疾病（CAD）。我们 这些成就为临床相关性提供了进一步支持， 心脏PET成像的MBF和代谢，并提供新的见解， 心肌缺血的病理生理学我们认为， 只有在更严格的控制下， 动物实验室的条件。因此，我们希望重新关注 拟议的血管运动改变的非侵入性评估研究 在CAD的发展早期以及在临床表现的CAD中。的 有待检验的假设是， 临床前和临床CAD可以用MBF非侵入性地证实 通过N-13氨和PET的测量， 饮食，生活方式和药物干预可以证明， 非侵入性地。我们将通过解决四个具体问题来验证我们的假设。 问题：（l）短期心血管调节是否改善 冠心病患者的心肌血流储备和血管舒张功能， 这些因素是导致这种改善的原因吗？(2)临床前CAD是否可以 通过压力干预来识别？(3)异常的冠状动脉血管运动 在慢性吸烟者中确定;在CAD中加重但改善 通过戒烟？(4)急性和慢性雌激素给药 在患有CAD或有CAD风险绝经后妇女中， 血管舒缩和预防CAD？我们将解决这些问题 通过使用N-13对区域MBF进行准确和可重复的测量， 氨，动态PET和先前验证的示踪剂动力学模型， 休息时，在静脉注射诱导充血和应激激发期间， 正常志愿者、临床前和显性CAD患者， 绝经后妇女。在这些期间，连续测量MBF 将在心血管手术之前和之后进行干预 调节，戒烟和慢性雌激素替代期间，我们 预计研究目标的实现将提供一个 用于检测早期、临床前CAD的无创工具， 直接证明了广泛倡导的干预措施的有效性， 例如定期锻炼、降脂饮食、生活方式的改变， 戒烟以延缓或逆转CAD的进展，甚至 雌激素的预防和保护心血管作用 在有CAD风险的绝经后妇女中进行置换。