In the last decade, rapidly evolving technical developments have allowed progressively more sophisticated nuclear magnetic resonance (NMR) experiments to investigate bioenergetics and metabolism. In the current application, we propose to continue this research strategy, focusing on development of NMR methodology and applications to physiological questions in animal models of increasing complexity that approach the in vivo conditions. New spatially localized 31P spectroscopy and NMR imaging techniques will be used in the closed-chest, intact, dog model to investigate the general physiological questions of i) the regulation of oxidative phosphorylation and ATP consumption rates in the myocardium in vivo, and ii) the consequences of reversible myocardial ischemia and """"""""stunning"""""""" in vivo. The physiological questions focus on the central role proposed for perfusion and ATP demand in dictating control of ATP synthesis and utilization rate, and determining perturbations due to ischemia secondary to either partial coronary artery occlusion under basal conditions or increased demand in the presence of a flow limiting stenosis. In addition, the proposed physiological studies will investigate unexpected transmural gradients that result from divergent gradients of perfusion and ATP demand under high workload conditions.
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