Liver oxygen uptake dependence and mitochondrial function in septic rats.

Abstract

Defective oxygen consumption and a pathological dependence of oxygen uptake on O2 supply have been considered important events in sepsis. To relate these features with tissue and mitochondrial metabolism, we studied oxygen uptake in whole isolated and perfused rat liver at two O2 supply levels, in the same liver slices, and in isolated liver mitochondria. Experimental sepsis in rats was induced by cecal ligation and double-gauge puncture. The results showed that liver and tissue slices from septic animals had a 60% greater O2 uptake than that of controls and that, during sepsis, liver O2 uptake was markedly dependent on O2 supply. Concomitantly, mitochondrial O2 uptake was nearly 30% greater with malate-glutamate as substrate, but not with succinate; lowering O2 concentration in the medium did not alter the enhanced function. In submitochondrial, only NADH-dehydrogenase activity was 100% higher in septic samples. At least, in some tissues, O2 dependence is a function of O2 availability, sensitized by increased mitochondrial O2 uptake related to changes in respiratory enzymes.