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

Dysoxia can be defined as ATP flux decreasing in proportion to O2availability with preserved ATP demand. Hepatic venous β-hydroxybutyrate-to-acetoacetate ratio (β-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 β-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 O2availability was taken as O2uptake (V˙o2) decreasing in proportion to O2delivery (Q˙o2); and preserved ATP demand was taken as increasing Pi/ATP.V˙o2, tissue Pi/ATP, and venous β-OHB/AcAc were plotted againstQ˙o2to identify critical inflection points. Tissue dysoxia required meanQ˙o2for the group to be critical for bothV˙o2and for Pi/ATP. CriticalQ˙o2values forV˙o2and Pi/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 V˙o2began decreasing, i.e., that there could have been “O2conformity.” CriticalQ˙o2for venous β-OHB/AcAc was 2.44 ± 0.46 ml ⋅ 100 g−1⋅ min−1( P = NS), nearly the same as that for Pi/ATP, supporting venous β-OHB/AcAc as a detector of dysoxia. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector of dysoxia in liver.