RELATION OF MYOCARDIAL OXYGEN-CONSUMPTION AND FUNCTION TO HIGH-ENERGYPHOSPHATE UTILIZATION DURING GRADED HYPOXIA AND REOXYGENATION IN SHEEP IN-VIVO

This study investigates the relation between myocardial oxygen consump tion (MV o(2)), function, and high energy phosphates during severe hyp oxia and reoxygenation in sheep in vivo, Graded hypoxia was performed in open-chested sheep to adjust Po-2 to values where rapid depletion o f energy stores occurred, Highly time-resolved P-31 nuclear magnetic r esonance spectroscopy enabled monitoring of myocardial phosphates thro ughout hypoxia and recovery with simultaneous MV o(2) measurement, She ep undergoing graded hypoxia (n = 5) with an arterial Pot nadir of 13. 4+/-0.5 mmHg, demonstrated maintained rates of oxygen consumption with large changes in coronary how as phosphocreatine (PCr) decreased with in 4 min to 40+/-7% of baseline, ATP utilization rate increased simult aneously 59+/-20%, Recovery was accompanied by marked increases in MV o(2) from 2.0+/-0.5 to 7.2+/-1.9 mu mol/g per min, while PCr recovery rate was 4.3+/-0.6 mu mol/g per min, ATP decreased to 75+/-6% of basel ine during severe hypoxia and did not recover, Sheep (n = 5) which und erwent moderate hypoxia (Po-2 maintained 25-35 mmHg for 10 min) did no t demonstrate change in PCr or ATP, Functional and work assessment (n = 4) revealed that cardiac power increased during the graded hypoxia a nd was maintained through early reoxygenation, These studies show that (a) MV Oz does not decrease during oxygen deprivation in vivo despite marked and rapid decreases in high energy phosphates; (b) contractile function during hypoxia in vivo does not decrease during periods of P Cr depletion and intracellular phosphate accumulation, and this may be related to marked increases in circulating catecholamines during glob al hypoxia. The measured creatine rephosphorylation rate is 34+/-11% o f predicted (P < 0.01) calculated from reoxygenation parameters, which indicates that some mitochondrial respiratory uncoupling also occurs during the rephosphorylation period.