title: Recovery of energy metabolism in rat brain after carbon monoxide hypoxia.
abstract: Carbon monoxide (CO) may inhibit mitochondrial electron transport in the brain and increase the toxic effects of the gas. This hypothesis was investigated in anesthetized rats during CO exposure and recovery at either normobaric or hyperbaric O2 concentrations. During exposure and recovery, we measured the oxidation level of cerebrocortical cytochrome c oxidase by differential spectroscopy and biochemical metabolites known to reflect aerobic energy provision in the brain. CO exposure (HbCO = 71 +/- 1%) significantly decreased blood pressure and cytochrome oxidation level. Cerebral ATP was maintained while lactate/pyruvate, glucose, and succinate rose, and phosphocreatine (PCr) fell, relative to control (P less than 0.05). Intracellular pH (pHi) calculated from the PCr equilibrium also declined during the exposures. During recovery, HbCO fell more rapidly at hyperbaric than at normobaric O2 levels, but returned to 10% or less in both groups by 45 min. Cytochrome oxidation state improved to 80% of control after 90 min at normobaric O2, but recovered completely after hyperbaric O2 (P less than 0.05). In normobaric O2, PCr and pHi continued to fall for 45 min after CO exposure and did not recover completely by 90 min. PCr and pHi in animals after hyperbaric O2 improved within 45 min, but also remained below control at 90 min. These data indicate that intracellular uptake of CO can impair cerebral energy metabolism, despite the elimination of HbCO from the blood.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: S D
authors.initials: SD
authors.lastname: Brown
authors.forename: C A
authors.initials: CA
authors.lastname: Piantadosi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002248:Carbon Monoxide / Q000633:toxicity*; D002263:Carboxyhemoglobin / Q000032:analysis; D004734:Energy Metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002248:Carbon Monoxide; D002263:Carboxyhemoglobin