IN VIVO HEART PROTEIN METABOLISM IN DIABETES & ISCHEMIA

应聘者是一位受过临床训练的心脏病专家，对心脏病感兴趣。 代谢及其在心脏病研究中的应用。目标是 计划研究的一部分是为候选人提供广泛的 作为一个独立的人追求这种兴趣所必需的科学训练 调查员和学术心脏病专家。 体内蛋白质周转的生理学测量还没有被 以前是以非破坏性方式完成的。的具体目的 拟议中的研究涉及开发一种同位素稀释剂。 在体心脏氨基酸利用和蛋白质研究技术 新陈代谢。这项技术将在意识清醒的狗身上得到验证和应用 模型，以期其在临床研究中的应用。 检测蛋白质生理调节的实验方法 正常狗的代谢将包括胰岛素钳，底物 静脉注射，以及生长抑素抑制胰岛素。中的更改 将研究糖尿病和心肌缺血动物的新陈代谢。 蛋白质和氨基酸代谢异常可能导致 糖尿病患者存在心脏储备异常和心肌病变。 心肌缺血时氨基酸和蛋白质代谢的改变可能 对缺血恢复的速度和程度很重要。进一步 了解心脏蛋白质代谢的病理生理学可能 直接影响糖尿病患者的治疗 急性心肌再灌注后缺血性损伤的恢复 脑梗塞。 心脏病和内分泌科与 分子生物学和生物化学系建立了强大的 耶鲁大学心脏和骨骼领域的跨学科背景 肌肉新陈代谢。测量冠状动脉血流量的方法，心脏 血流动力学，以及全球和局部心脏功能 可在心脏病科获得。研究这些影响的技术 胰岛素和代谢底物对狗蛋白质周转的影响 用于内分泌科。同样，在衡量的专业知识 用核磁共振波谱测定高能磷酸盐水平已被开发出来。 这样的环境将为应聘者提供坚实的背景 培训以发展为心脏领域的独立研究人员 新陈代谢。

The candidate is a clinically trained cardiologist interested in cardiac metabolism and its application to the study of cardiac disease. The goal of the projected research is to provide the candidate with the broad scientific training necessary to pursue this interest as an independent investigator and academic cardiologist. Physiologic measurement of protein turnover in vivo has not been accomplished previously in a non-destructive fashion. The specific aim of the proposed research involves the development of an isotope dilution technique to study in vivo cardiac amino acid utilization and protein metabolism. The technique will be validated and applied in a conscious dog model, in anticipation of its utilization in clinical investigation. Experimental methods to examine the physiologic regulation of protein metabolism in normal dogs will include the insulin clamp, substrate infusion, and insulin suppression with somatostatin. Alterations in metabolism in animals with diabetes and myocardial ischemia will be studied. Abnormalities in protein and amino acid metabolism may contribute to the abnormal cardiac reserve and cardiomyopathy observed in diabetic patients. Alterations in amino acid and protein metabolism in myocardial ischemia may be important to the rate and degree of recovery from ischemia. Further understanding of the pathophysiology of cardiac protein metabolism may impact directly on the treatment of patients wiht diabetes and those recovering from ischemic insult following reperfusion in acute myocardial infarction. Collaboration between the Divisions of Cardiology and Endocrinology and the Department of Molecular Biology and Biochemistry has established a strong interdisciplinary background at Yale in the area of cardiac and skeletal muscle metabolism. The methods to measure coronary blood flow, cardiac hemodynamics, and both global and regional cardiac performance are available in the Cardiology Division. Techniques to study the effects of insulin and metabolic substrates on protein turnover in the dog have been used in the Endocrine Division. Likewise, expertise in the measurement of high energy phosphate levels by NMR spectroscopy has been developed. This environment will provide the candidate with the solid background training to develop as an independent investigator in the area of cardiac metabolism.