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

Dysoxia can be defined as ATP flux decreasing in proportion to O2 availability 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 O2 availability was taken as O2 uptake (V˙o 2) decreasing in proportion to O2 delivery (Q˙o 2); and preserved ATP demand was taken as increasing Pi/ATP.V˙o 2, tissue Pi/ATP, and venous β-OHB/AcAc were plotted againstQ˙o 2to identify critical inflection points. Tissue dysoxia required meanQ˙o 2for the group to be critical for bothV˙o 2 and for Pi/ATP. CriticalQ˙o 2values forV˙o 2 and Pi/ATP of 4.07 ± ...