NMR STUDIES OF CONGESTIVE HEART FAILURE

我们建议实施原子核的31P和13C生物物理方法 磁共振波谱在充血性心力衰竭研究中的应用 (CHF)在狗的心脏内跨壁存活。慢性心力衰竭是一种复杂的 临床表现为心血管疾病复杂的相互作用， 肾脏、内分泌和肺部系统。尽管情况非常严峻 对于这种情况的预后，关于 伴随充血性心力衰竭的跨壁代谢变化。因此，瑞士法郎将 在狗的二尖瓣关闭不全模型中进行研究，实施 允许对功能、血流和新陈代谢进行跨壁分析。 犬CHF的跨壁核磁共振研究是基于对 正常的左心室，就其本质而言，与生俱来 收缩压、血流量、氧分压和代谢物的梯度 和酶的水平。这种心肌壁内的不均一性 心外膜和心内膜之间的关系在缺血时很明显，而且是 极有可能在充血性心力衰竭中发挥重要作用。犬类模型是 通过的目的是为了解决必须从以下方面进行研究的问题 生理生化原因。 在本提案中，将涉及两个生化领域：1)底物 利用率和2)跨壁肌酸激动率。CHF很可能会 包括在底物利用率水平和作为一个 结果，这些研究将在正常和失败的心脏中进行。 我们将监测缺血性损伤前后的情况 机械功能、ATP合成与细胞止血 小鼠体内组织中ATP、CP、PI和H+水平与工作负荷的关系 充血性心力衰竭时犬心脏的糖酵解和氧化过程 使用富含13C的丙酮酸、棕榈酸酯和葡萄糖进行研究。在……里面 此外，跨壁肌酸激动率将使用31 P-核磁共振饱和转移技术。

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.