NMR STUDIES OF CONGESTIVE HEART FAILURE

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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.