title: Hepatic dysoxia commences during O2 supply dependence.
abstract: Hepatic O2 consumption (VO2) remains relatively constant (O2 supply independent) as O2 delivery (DO2) progressively decreases, until a critical DO2 (DO2c) is reached below which hepatic VO2 also decreases (O2 supply dependence). Whether this decrease in VO2 represents an adaptive reduction in O2 demand or a manifestation of tissue dysoxia, i.e., O2 supply that is inadequate to support O2 demand, is unknown. We tested the hypothesis that the decrease in hepatic VO2 during O2 supply dependence represents dysoxia by evaluating hepatic mitochondrial NAD redox state during O2 supply independence and dependence induced by progressive hemorrhage in six pentobarbital-anesthetized dogs. Hepatic mitochondrial NAD redox state was estimated by measuring hepatic venous beta-hydroxybutyrate-to-acetoacetate ratio (beta OHB/AcAc). The value of DO2c was 5.02 +/- 1.64 (SD) ml.100 g-1.min-1. The beta-hydroxybutyrate-to-acetoacetate ratio was constant until a DO2 value (3.03 +/- 1.08 ml.100 g-1.min-1) was reached (P = 0.05 vs. DO2c) and then increased linearly. Peak liver lactate extraction ratio was 15.2 +/- 14.1%, occurring at a DO2 of 5.48 +/- 2.54 ml.100 g-1.min-1 (P = NS vs. DO2c). Our data support the hypothesis that the decrease in VO2 during O2 supply dependence represents tissue dysoxia.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, Pennsylvania.
authors.forename: R
authors.initials: R
authors.lastname: Schlichtig
authors.forename: H A
authors.initials: HA
authors.lastname: Klions
authors.forename: D J
authors.initials: DJ
authors.lastname: Kramer
authors.forename: E M
authors.initials: EM
authors.lastname: Nemoto
mesh_terms: D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D004285:Dogs; D006470:Hemorrhage / Q000378:metabolism; D006885:Hydroxybutyrates / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption
chemical_list: D000090:Acetoacetates; D006885:Hydroxybutyrates; D007773:Lactates; D009243:NAD; D019344:Lactic Acid; C016635:acetoacetic acid; D020155:3-Hydroxybutyric Acid