IN VIVO HEART PROTEIN METABOLISM IN DIABETES & ISCHEMIA

候选人是一名经过临床培训的心脏病专家，对心脏病感兴趣。 代谢及其在心脏病研究中的应用。 目标 项目研究的目的是为候选人提供广泛的 科学培训必要追求这一利益作为一个独立的 研究员和学术心脏病专家。 体内蛋白质周转的生理学测量尚未得到证实。 以前以非破坏性的方式完成。 具体目标是 拟议中的研究涉及开发同位素稀释法 研究体内心脏氨基酸利用和蛋白质技术 新陈代谢. 这项技术将在一只清醒的狗身上得到验证和应用 模型，以期待其在临床研究中的应用。 研究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 输注和用生长抑素抑制胰岛素。 的改变 将研究患有糖尿病和心肌缺血的动物的代谢。 蛋白质和氨基酸代谢的异常可能是导致 在糖尿病患者中观察到异常的心脏储备和心肌病。 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， 直接影响糖尿病患者的治疗， 急性心肌缺血再灌注损伤后的恢复 梗塞 心脏病学和内分泌学部门与 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 肌肉代谢 测量冠状动脉血流量、心脏 血流动力学以及整体和局部心脏性能， 在心脏科有售。 研究影响的技术 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 已经开发了通过NMR光谱测定高能磷酸盐水平的方法。 这样的环境将为候选人提供坚实的背景 培训，以发展成为心脏领域的独立研究者 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.