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.
| Rath, D P; Zhu, H; Tong, X et al. (1997) Dynamic 13C NMR analysis of pyruvate and lactate oxidation in the in vivo canine myocardium: evidence of reduced utilization with increased work. Magn Reson Med 38:896-906 |
| Rath, D P; Abduljalil, A M; Robitaille, P M (1993) Spatially localized 31P NMR measurements of longitudinal relaxation rates in the canine myocardium. Magn Reson Med 29:822-5 |
| Robitaille, P M; Rath, D P; Skinner, T E et al. (1993) Transaminase reaction rates, transport activities and TCA cycle analysis by post-steady state 13C NMR. Magn Reson Med 30:262-6 |
| Robitaille, P M; Rath, D P; Abduljalil, A M et al. (1993) Dynamic 13C NMR analysis of oxidative metabolism in the in vivo canine myocardium. J Biol Chem 268:26296-301 |
| Robitaille, P M; Abduljalil, A; Rath, D et al. (1993) Transmural saturation transfer analysis of the creatine kinase system in the mammalian heart. Magn Reson Med 30:4-10 |
