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

Michael K. Dishart, Robert Schlichtig*, Tor Inge Tønnessen, Ranna A. Rozenfeld, Elena Simplaceanu, Donald Williams, Timothy J P Gayowski

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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 (V̇O2) decreasing in proportion to O2 delivery (Q̇O2); and preserved ATP demand was taken as increasing P(i)/ATP. V̇O2, tissue P(i)/ATP, and venous β-OHB/AcAc were plotted against Q̇O2 to identify critical inflection points. Tissue dysoxia required mean Q̇O2 for the group to be critical for both V̇O2 and for P(i)/ATP. Critical Q̇O2 values for V̇O2 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 V̇O2 began decreasing, i.e., that there could have been 'O2 conformity.' Critical Q̇O2 for venous β-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 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.

Original languageEnglish (US)
Pages (from-to)791-797
Number of pages7
JournalJournal of applied physiology
Volume84
Issue number3
DOIs
StatePublished - Mar 1998

Keywords

  • Adenosine 5'-triphosphate
  • Ischemia
  • Nuclear magnetic resonance
  • Oxygen delivery
  • Pig

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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