MITOCHONDRIAL REDOX STATE AS A POTENTIAL DETECTOR OF LIVER DYSOXIA IN-VIVO

Dysoxia can be defined as ATP flux decreasing in proportion to O-2 ava ilability with preserved ATP demand. Hepatic venous beta-hydroxybutyra te-to-acetoacetate ratio (beta-OHB/AcAc) estimates liver mitochondrial NADH/NAD and may detect the onset of dysoxia. During partial dysoxia (as opposed to anoxia), however, flow may be adequate in some liver re gions, diluting effluent from dysoxic regions, thereby rendering venou s beta-OHB/AcAc unreliable. To address this concern, we estimated tiss ue ATP while gradually reducing liver blood flow of swine to zero in a nuclear magnetic resonance spectrometer. ATP flux decreasing with O-2 availability was taken as O-2 uptake ((V) over dot O-2) decreasing in proportion to O-2 delivery ((Q) over dot O-2); and preserved ATP dema nd was taken as increasing P-i/ATP. Vet, tissue P-i/ATP, and venous be ta-OHB/AcAc were plotted against (Q) over dot O-2 to identify critical inflection points. Tissue dysoxia required mean (Q) over dot O-2 for the group to be critical for both (V) over dot O-2 and for P-i/ATP. Cr itical (Q) over dot O-2 values for (V) over dot O-2 and P-i/ATP of 4.0 7 +/- 1.07 and 2.39 +/- 1.18 (SE) ml.100 g(-1).min(-1), respectively, were not statistically significantly different but not clearly the sam e, suggesting the possibility that dysoxia might have commenced after (V) over dot O-2 began decreasing, i.e., that there could have been '' O-2 conformity.'' Critical (Q) over dot O-2 for venous beta-OHB/AcAc w as 2.44 +/- 0.46 ml.100 g(-1).min(-1) (P = NS), nearly the same as tha t for P-i/ATP, supporting venous beta-OHB/AcAc as a detector of dysoxi a. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector of dysoxia in liver.