This study investigates the relation between myocardial oxygen consumption (MVO2), function, and high energy
phosphates during severe
hypoxia and reoxygenation in sheep in vivo. Graded
hypoxia was performed in open-chested sheep to adjust PO2 to values where rapid depletion of energy stores occurred. Highly time-resolved 31P nuclear magnetic resonance spectroscopy enabled monitoring of myocardial
phosphates throughout
hypoxia and recovery with simultaneous MVO2 measurement. Sheep undergoing graded
hypoxia (n = 5) with an arterial PO2 nadir of 13.4 +/- 0.5 mmHg, demonstrated maintained rates of oxygen consumption with large changes in coronary flow as
phosphocreatine (PCr) decreased within 4 min to 40 +/- 7% of baseline.
ATP utilization rate increased simultaneously 59 +/- 20%. Recovery was accompanied by marked increases in MVO2 from 2.0 +/- 0.5 to 7.2 +/- 1.9 mumol/g per min, while PCr recovery rate was 4.3 +/- 0.6 mumol/g per min.
ATP decreased to 75 +/- 6% of baseline during severe
hypoxia and did not recover. Sheep (n = 5) which underwent moderate
hypoxia (PO2 maintained 25-35 mmHg for 10 min) did not demonstrate change in PCr or
ATP. Functional and work assessment (n = 4) revealed that cardiac power increased during the graded
hypoxia and was maintained through early reoxygenation. These studies show that (a) MVO2 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 PCr depletion and intracellular
phosphate accumulation, and this may be related to marked increases in circulating
catecholamines during global
hypoxia. The measured
creatine rephosphorylation rate is 34 +/- 11% of predicted (P < 0.01) calculated from reoxygenation parameters, which indicates that some mitochondrial respiratory uncoupling also occurs during the rephosphorylation period.