LIVER OXYGEN-UPTAKE DEPENDENCE AND MITOCHONDRIAL-FUNCTION IN SEPTIC RATS

Defective oxygen consumption and a pathological dependence of oxygen u ptake on O-2 supply have been considered important events in sepsis. T o relate these features with tissue and mitochondrial metabolism, we s tudied oxygen uptake in whole isolated and perfused rat liver at two O -2 supply levels, in the same liver slices, and in isolated liver mito chondria. Experimental sepsis in rats was induced by cecal ligation an d double-gauge puncture. The results showed that liver and tissue slic es from septic animals had a 60% greater O-2 uptake than that of contr ols and that, during sepsis, liver O-2 uptake was markledy dependent o n O-2 supply. Concomitantly, mitochondrial O-2 uptake was nearly 30% g reater with malate-glutamate as substrate, but not with succinate; low ering O, concentration in the medium did not alter the enhanced functi on. In submitochondrial particles, only NADH-dehydrogenase activity wa s 100% higher in septic samples. At least, in some tissues, O-2 depend ence is a function of O-2 availability, sensitized by increased mitoch ondrial O-2 uptake related to changes in respiratory enzymes. (C) 1995 Wiley-Liss, Inc.