Augmented energy consumption during early systole as a mechanism of cyclical changes in high-energy phosphates in myocardium assessed by phosphorus nuclear magnetic resonance

To evaluate the underlying mechanism of oscillatory changes in energy-related metabolites during a cardiac cycle, intramyocardial creatine phosphate (CP), inorganic phosphate (Pi), adenosine triphosphate (ATP), adenosine diphosphate (ADP) and pH were measured in isolated rat hearts by the phosphorus nuclear magnetic resonance spectrometry method gated by the left ventricular pressure. These were perfused with modified Krebs-Henseleit solution containing pyruvate. CP decreased at both early- and end-systole whereas Pi and ADP increased in these phases. Both ATP and intracellular pH decreased significantly at end-systole. The indices of the affinity for ATP hydrolysis [Pi]/[CP] and [ADP] [Pu]/[APT] increased at early-systole, indicating that a large consumption of high-energy phosphates occurred at early-systole. Furthermore, the cyclical changes in ATP, CP and Pi were augmented in the high contractile state induced by infusion of isoproterenol. These results strongly suggest that the cyclical changes in the energy-related metabolites during a cardiac cycle are caused mainly by an augmentation of energy consumption during early-systole and an insufficient energy supply during systole, probably due to the slow intracellular transport of CP.