Mitochondrial redox state as a potential detector of liver dysoxia in vivo

Department of Research and Development, Veterans Affairs Medical Center, Pittsburgh 15240; and Departments of Anesthesiology and Critical Care Medicine, Internal Medicine, and Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15261 Dysoxia can be defined as ATP flux decreasing in proportion to O 2 availability with preserved ATP demand. Hepatic venous -hydroxybutyrate-to-acetoacetate ratio ( -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 regions, diluting effluent from dysoxic regions, thereby rendering venous -OHB/AcAc unreliable. To address this concern, we estimated tissue 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 ( O 2 ) decreasing in proportion to O 2 delivery ( O 2 ); and preserved ATP demand was taken as increasing P i /ATP. O 2 , tissue P i /ATP, and venous -OHB/AcAc were plotted against O 2 to identify critical inflection points. Tissue dysoxia required mean O 2 for the group to be critical for both O 2 and for P i /ATP. Critical O 2 values for O 2 and P i /ATP of 4.07 ± 1.07 and 2.39 ± 1.18 (SE) ml · 100 g 1 · min 1 , respectively, were not statistically significantly different but not clearly the same, suggesting the possibility that dysoxia might have commenced after O 2 began decreasing, i.e., that there could have been "O 2 conformity." Critical O 2 for venous -OHB/AcAc was 2.44 ± 0.46 ml · 100 g 1 · min 1 ( P = NS), nearly the same as that for P i /ATP, supporting venous -OHB/AcAc as a detector of dysoxia. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector of dysoxia in liver. adenosine 5'-triphosphate; nuclear magnetic resonance; oxygen delivery; ischemia; pig JAP 84(3):791-797 0161-7567/98 $5.00 Copyright © 1998 the American Physiological Society