NMR STUDIES OF CONGESTIVE HEART FAILURE

我们建议实施核的31 p和13 C生物物理方法 磁共振（NMR）光谱学研究充血性心力衰竭 (CHF)在狗心脏中的体内透壁。 CHF是一个复杂的 临床情况的特点是复杂的相互作用， 肾、内分泌和肺系统。 尽管有非常严峻的 对于这种情况的预后，相对而言， 充血性心力衰竭伴随的透壁代谢变化。 因此，CHF将 在犬的二尖瓣返流模型中进行研究， 允许功能、血流和代谢的透壁分析。 狗CHF的透壁NMR研究是基于认识到 正常的左心室，就其本质而言， 收缩压梯度、血流量、氧分压和代谢产物 和酶水平。 心肌壁内的这种不均匀性 在局部缺血中，表膜和内皮细胞之间的联系是显而易见的， 很可能在CHF中发挥重要作用。 犬模型是 通过的问题，必须研究transmurally， 生理和生化原因。 在本提案中，将涉及两个生物化学领域：1）底物 利用率和2）跨壁肌酸激酶率。 CHF可能会 包括底物利用水平的几个变化， 结果，这些研究将在正常和失败的心脏中进行， 缺血性损伤之前和之后的条件，我们将监测 机械功能、ATP合成和细胞止血 ATP、CP、Pi和H+的组织水平作为体内工作负荷的函数， CHF中的糖酵解和氧化过程也将 使用富含13C的丙酮酸盐、棕榈酸盐和葡萄糖进行研究。 在 此外，跨壁肌酸激酶率将使用31 P-NMR饱和转移技术。

We propose to implement the 31p and 13C biophysical approaches of nuclear magnetic resonance (NMR) spectroscopy to study congestive heart failure (CHF) transmurally in vivo in the dog heart. CHF is a complicated clinical situation marked by a complex interplay of the cardiovascular, renal, endocrine and pulmonary systems. In spite of the very grim prognosis for this condition, relatively little is known regarding the transmural metabolic changes that accompany CHF. As a result, CHF will be studied in a mitral regurgitation model in the dog, implemented to permit the transmural analysis of function, blood flow and metabolism. The transmural NMR studies of CHF in the dog are based on the recognition that the normal left ventricle, by its very nature, possesses inherent gradients in systolic stress, blood flow, oxygen tension, and metabolite and enzyme levels. This non-uniformity within the myocardial wall between the epi- and endocardium is readily apparent in ischemia and is very likely to play an important role in CHF. The canine model was adopted to address issues that must be studied transmurally for physiological and biochemical reasons. In this proposal two biochemical areas will be addressed: 1) substrate utilization and 2) transmural creatine kinase rates. CHF is likely to encompass several changes at the substrate utilization level and as a result, these studies will take place in hearts under normal and failing conditions both prior to and following an ischemic insult We will monitor mechanical function, ATP synthesis and cell hemostasis by examining tissue levels of ATP, CP, Pi and H+ as a function of workload in vivo in the canine heart The glycolytic and oxidative processes in CHF will also be studied using 13C enriched pyruvate, palmitate, and glucose. In addition, transmural creatine kinase rates will be assessed using 31 P-NMR saturation transfer techniques.