NMR STUDIES OF MYOCARDIAL METABOLISM IN VIVO

当冠脉血流突然中断时，心肌收缩 缺血区在几秒钟内就会变得凹陷。生物化学 这种缺血性功能障碍的机制还不是很清楚。我们的目标是 评估特定高能磷酸盐耗竭的作用 化合物、组织酸中毒和缺血型心肌乳酸蓄积 功能障碍。为此，我们将使用1H和31P核磁共振 (核磁共振)光谱方法，结合同时测量 局部和整体心功能及局部心肌血 人流，利用优越的设施和人员 耶鲁大学提供的生物核磁共振波谱以及PI的独一无二 有心脏病学、数学、计算机科学和核磁共振背景。 使用气囊封堵器将使狗遭受可逆性缺血 在左冠状动脉前降支周围，而核磁共振光谱是 使用放置在缺血区或 心肌的控制区。我们希望通过这种方式定义一种新陈代谢 可逆性功能障碍组织的“特征”。我们亦会研究 再灌流和抗缺血及变力药物治疗的效果。 在该项目的最后两年半时间里，我们将尝试开发 实现核磁共振波谱分析的本地化技术 闭胸狗和人类。我们将首先将此应用于 为验证心肌病体积定位方法的准确性， 然后是从急性前壁心肌梗死中恢复的患者。 这些信息对于理解 人类冠状动脉疾病的病理生理学发展得更好 心血管诊断技术和设计新的治疗药物 适用于急性和慢性缺血。

When coronary blood flow is suddenly interrupted, myocardial contraction in the ischemic area becomes depressed within seconds. The biochemical mechanism of this ischemic dysfunction is not well understood. Our goal is to evaluate the role of depletion of specific high-energy phosphate compounds, tissue acidosis, and lactate accumulation in ischemic myocardial dysfunction. To do this, we will use 1H and 31P nuclear magnetic resonance (NMR) spectroscopic methods, coupled with simultaneous measurement of regional and global ventricular function and of regional myocardial blood flow, taking advantage of the exceptional facilities and personnel availabale at Yale for biologic NMR spectroscopy as well as the PI's unique background in cardiology, mathematics, computer science, and NMR. Dogs will be subjected to reversible ischemia using a balloon occluder around the left anterior descending coronary artery, while NMR spectra are collected using surface coils positioned over either the ischemic or the control regions of myocardium. In this way we hope to define a metabolic "signature" of reversibly dysfunctional tissue. We will also study the effects both of reperfusion and of anti-ischemic and inotropic drug therapy. In the last 2 1/2 years of the project we will attempt to develop volume localization techniques to make it possible to perform NMR spectroscopy in the closed chest dog and in humans. We will apply this first to cardiomyopathy to verify the accuracy of the volume localization methods, and then to patients recovering from acute anterior myocardial infarction. Such information is potentially important in understanding the pathophysiology of human coronary artery disease, developing better cardiovascular diagnostic techniques, and designing new therapeutic agents for acute and chronic ischemia.