CARDIAC HIGH-ENERGY PHOSPHATES ADAPT FASTER THAN OXYGEN-CONSUMPTION TO CHANGES IN HEART-RATE

To investigate the dynamic control of cardiac ATP synthesis, we simult aneously determined the time course of mitochondrial oxygen consumptio n with the time course of changes in high-energy phosphates following steps in cardiac energy demand. Isolated isovolumically contracting ra bbit hearts were perfused with Tyrode's solution at 28 degrees C (n=7) or at 37 degrees C (n=7). Coronary arterial and venous oxygen tension s were monitored with fast-responding oxygen electrodes. A cyclic paci ng protocol in which we applied 64 step changes between two different heart rates was used. This enabled nuclear magnetic resonance measurem ent of the phosphate metabolites with a time resolution of approximate to 2 seconds. Oxygen consumption changed after heart-rate steps with time constants of 14+/-1 (mean+/-SEM) seconds at 28 degrees C and 11+/ -1 seconds at 37 degrees C, which are already corrected for diffusion and vascular transport delays. Doubling of the heart rate resulted in a significant decrease in phosphocreatine (PCr) content (11% at 28 deg rees C, 8% at 37 degrees C), which was matched by an increase in inorg anic phosphate (P-i) content, although oxygen supply was shown to be n onlimiting. The time constants for the change of both Pi and PCr conte nt, approximate to 5 seconds at 28 degrees C and 2.5 seconds at 37 deg rees C, are significantly smaller than the respective time constants f or oxygen consumption. The changes in phosphate metabolites during cha nges in oxygen consumption suggest that regulation of oxidative phosph orylation could occur partly via products of ATP hydrolysis, but the u nequal time constants of PCr and oxygen consumption suggest that other regulatory mechanisms also play a role. These dissimilar time constan ts further suggest that there might be an appreciable transient contri bution of nonaerobic, presumably glycolytic, ATP synthesis to buffer t he high-energy phosphates during fast transitions in cardiac work.