POSITRON TOMOGRAPHY IN ISCHEMIC HEART DISEASE

正电子发射断层扫描(PET)的定量动态成像 在过去的资助中，N-13氨、C-11乙酸盐和F-18脱氧葡萄糖 定量局部心肌血流量(MBF)的时间 以及心肌梗死后早期患者的底物代谢 脑梗塞或慢性冠状动脉疾病(CAD)。我们的 成就为临床相关性提供了进一步的支持 心脏PET对MBF和代谢的成像提供了新的见解 心肌缺血的病理生理学。我们认为，额外的 机械性信息只有在更多的控制下才能获得 动物实验室的条件。因此，我们希望重新关注 血管运动异常的非侵入性评估研究进展 在CAD的早期发展以及临床表现的CAD中。这个 有待检验的假设是冠状动脉血管运动异常 MBF可无创性显示临床前和临床中的CAD N-13氨水和正电子发射体素测定及其有益效果 可以演示饮食、生活方式和药物干预 非侵入性的。我们将通过处理四个具体的问题来验证我们的假设 问题：(L)短期心血管调节是否有所改善 冠心病患者的心肌血流储备和血管扩张剂能力 这些改善的因素是什么？(2)临床前冠心病是否可以 通过应激干预确定？(3)冠状动脉血管运动异常 在长期吸烟者中被发现；它在CAD中加重但得到改善 通过戒烟？(4)急性和慢性雌激素治疗 患有或有冠心病风险的绝经后妇女改善异常 血管舒缩和预防冠心病？我们将解决这些问题 通过N-13对区域MBF的准确和可重复性的测量 氨、动态PET和先前验证的示踪剂动力学模型 休息，在药物引起的充血和应激刺激期间 正常志愿者、临床前和显性冠心病患者以及 绝经后的女性。在这期间的MBF的连续测量 干预将在心血管疾病之前和之后进行 条件反射、戒烟和慢性雌激素替代治疗 预期研究目标的完成将提供一个 用于检测早期临床前CAD的非侵入性工具 直接证明了广泛倡导的干预措施的有效性，如 例如，定期锻炼、降脂饮食、改变生活方式和 戒烟延缓或逆转冠心病的进展，甚至 雌激素的预防和心血管保护作用 有冠心病风险的绝经后妇女的替代治疗。

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.