Cardiac High-Energy Phosphates AdaptFaster ThanOxygenConsumption toChanges inHeartRate

Toinvestigate thedynamic control ofcardiac ATP synthesis, wesimultaneously determined thetimecourse of mitochondrial oxygenconsumption withthetimecourse of changes inhigh-energy phosphates following steps incardiac energydemand. Isolated isovolumically contracting rabbit hearts wereperfused withTyrode's solution at28°C(n=7) or at37°C(n=7). Coronary arterial andvenous oxygen tensions weremonitored withfast-responding oxygenelectrodes. A cyclic pacing protocol inwhichweapplied 64stepchanges between twodifferent heart rates wasused. Thisenabled nuclear magnetic resonance measurement ofthephosphate metabolites withatimeresolution of=2seconds. Oxygen consumption changed after heart-rate steps withtimecon- stants of14±1(mean±SEM) seconds at28°Cand11±1 seconds at37°C, which arealready corrected fordiffusion and vascular transport delays. Doubling oftheheart rateresulted inasignificant decrease inphosphocreatine (PCr) content (11%at28°C, 8%at37°C), which wasmatched byanincrease W rhencardiac workloadincreases suddenly, a concomitant increase inthehydrolysis of ATP occurs. Sincemyocardial reserves of high-energy phosphates arelimited, only brief deficits in ATPsynthesis canbetolerated without deterioration of contractile performance. Hence, ATPproduction must adapt fast tomatchATPhydrolysis. ATP canbegenerated inthemyocardium bytwo metabolic pathways: glycolysis andoxidative phosphor- ylation. Themajority ofATPisproduced bythelatter pathway.' Thefirst explanations fortheregulation of mitochondrial ATPproduction emphasized therole of ADP andinorganic phosphate (P,).23 Thesephosphate metabolites wouldserveasa feedback signal and thereby adequately regulate mitochondrial ATP pro- duction. Later, several authors reported thatthey were notable todetect changes inhigh-energy phosphates or intheproducts ofATP hydrolysis after achange in cardiac workloadinvivo.4-7 Thelackofdetectable