Effects of Halothane and Decreased PO2 on High Energy Phosphate Levels Maintained by Isolated Rat Liver Mitochondria

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Abstract
Steady stated of oxidative phosphorylation were achieved in mitochondrial suspensions continuously equilibrated with constant gas mixtures, simulating the conditions under which mitochondria contribute to the cellular energy status in vivo. The dependence of the mitochondria-maintained adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio on oxygen and halothane levels was examined at predetermined, clinically relevant concentrations of both gases. Inclusion of 1% halothane in the gas mixture decreased ATP/ADP by about half when mitochondrial respiration was supported by NAD-linked substrate (glutamate); succinate-supported ATP/ADP was not inhibited. With either substrate, and whether or not 1% halothane was present, ATP/ADP was unaffected by decreases in PO2 to values as low as 1.6 mm Hg. Under a range of typical in vivo conditions, therefore, 1% halothane significantly inhibited the mitochondrial contribution to steady state energy balance, whereas decreases in PO2 did not. Combined effects of 1% halothane and reduced PO2 on ATP/ADP were not seen, i.e., halothane did not increase the critical PO2 level (hypoxic threshold) for inhibition of mitochondrial ATP production.