NMR STUDIES OF CONGESTIVE HEART FAILURE

描述：在这份提案中，调查人员概述了一系列 进一步的实验旨在检验他的假设，即心脏 充血性心力衰竭(CHF)显示跨室壁磷的差异 高工作负荷下的代谢物，并显示出 碳基质的分解代谢。 将使用局域和非局域31P和13C核磁共振技术 用于功能、血流和新陈代谢的跨壁分析 心动过速犬模型。13C核磁共振实验，使用各种13C- 富含底物，旨在阐明几种生化 问题，包括底物选择和底物的变化 三氯乙烷循环中的利用率。31P核磁共振将用于监测 测定心肌细胞内pH和磷代谢产物水平 空间定位方法检验CHF改变心脏功能的假说 心肌支持机械和细胞功能的能力 最好的情况是，这些变化在 高负荷时的心内膜组织。饱和转移方法将 也可以用来测量通过肌酸激酶反应的通量 脑室壁。更多的实验将阐明这些变化 在心力衰竭发作之前，并检查心力衰竭的综合影响 和急性缺血性损伤。

DESCRIPTION: In this proposal the investigator outlines a series of further experiments designed to test his hypotheses that hearts in congestive heart failure (CHF) show transmural differences in phosphorus metabolites under high workloads and demonstrate alterations in the catabolism of carbon substrates. Localized and non-localized 31P and 13C NMR techniques will be used to for transmural analysis of function, blood flow, and metabolism in a tachycardiac dog model. 13C NMR experiments, using a variety of 13C- enriched substrates, are designed to elucidate several biochemical questions, including changes in substrate selection and in substrate utilization in the TCA cycle. 31P NMR will be used to monitor intracellular myocardial pH and phosphorus metabolite levels using spatial localization methods to test the hypotheses that CHF alters the myocardium's ability to support mechanical and cellular functions optimally, and that these alterations will be more pronounced in endocardial tissue at high workloads. Saturation transfer methods will also be used to measure flux though the creatine kinase reaction across the ventricular wall. Additional experiments will elucidate the changes which precede the onset of CHF and examine the combined effects of CHF and acute ischemic injury.