In order to maintain normal cardiac function, myocardial ATP synthesis (by oxidative phosphorylation) must be matched precisely to the rate of ATP hydrolysis, which in turn varies rapidly and widely with changing cardiac work. The control mechanisms which couple these processes are uncertain in the left ventricle (LV), and have not been investigated in the right ventricle (RV). A growing body of in vitro data, as well as in vivo observations from this laboratory, indicate that energy metabolism of the RV and LV may differ substantially; therefore, observations made in the LV may not be applicable to the RV. For example, when equal increases in RV oxygen consumption are produced by pulmonary artery constriction or isoproterenol infusion, opposite changes in the phosphocreatine/ATP ratio are observed: a decrease with PA constriction and an increase with isoproterenol. In addition, these two interventions are associated with marked differences in RV substrate uptake. This application proposes to utilize techniques of in vivo NMR spectroscopy, and regional measurements of myocardial blood flow, oxygen and substrate utilization, and NADH fluorescence to address the following questions in the pig heart in situ: Do changes in phosphate metabolites and mitochondrial redox potential both contribute to the regulation of oxidative phosphorylation in the RV? When does each exert predominant control? Do changes in substrate utilization affect the levels of RV phosphate metabolites and redox potential? In the same animal model, are there differences in the energetic responses to increased workload of the RV versus the LV? It is hoped that the answers to these questions will shed light on the control of a critical physiologic process, and elucidate similarities and differences in the energy metabolism of the two ventricles.
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