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Research Article| Volume 76, ISSUE 4, P569-583, October 1970

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Cerebral energy metabolism in short-chain fatty acid-induced coma

  • C.O. Walker
    Correspondence
    Reprint requests: Dr. Charles O. Walker, Department of Internal Medicine, Southwestern Medical School, 5323 Harry Hines Blvd., Dallas, Texas 75235.
    Affiliations
    From the Liver-Gastrointestinal Unit, Department of Internal Medicine, The University of Texas (Southwestern) Medical School at Dallas Dallas, Texas, USA
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  • D.W. McCandless
    Affiliations
    From the Liver-Gastrointestinal Unit, Department of Internal Medicine, The University of Texas (Southwestern) Medical School at Dallas Dallas, Texas, USA
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  • J.D. McGarry
    Footnotes
    Affiliations
    From the Liver-Gastrointestinal Unit, Department of Internal Medicine, The University of Texas (Southwestern) Medical School at Dallas Dallas, Texas, USA
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  • S. Schenker
    Footnotes
    Affiliations
    From the Liver-Gastrointestinal Unit, Department of Internal Medicine, The University of Texas (Southwestern) Medical School at Dallas Dallas, Texas, USA
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  • Author Footnotes
    ∗ Recipient of grant from the Dallas Diabetes Association.
    ∗∗ Recipient of Research Career Award 5 KO3 NB13746 from the United States Public Health Service.
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      Abstract

      Short-chain fatty acids (SCFA) have recently been incriminated as a cause of hepatic coma, and in vitro studies have suggested that the coma may be due to impaired cerebral energy metabolism. In this study, cerebral energy metabolism was assessed in vivo in rapidly frozen cortex and brainstem of rats with coma induced by administration of SCFA. The brainstem was evaluated separately because: (1) electroencephalograph changes in experimental SCFA-induced coma suggest brainstem involvement, and (2) this area of brain contributes importantly to maintenance of consciousness. Reversible coma of 38 to 67 minutes' duration was reproducibly induced in rats in 5 to 12 minutes by butyrate, valerate, or octanoate given intraperitoneally. Alert controls received equimolar sodium acetate or saline. Normal concentrations of adenosine triphosphate and phosphocreatine were found in both cerebral cortex and brainstem of rats at the onset of and during established SCFA-induced coma. Energy utilization rates in both brain areas, at the onset of coma, were also normal (
      • Lowry O.H.
      • Passonneau J.V.
      • Hasselberger F.X.
      • Schulz D.W.
      Effect of ischemia on known substrates and cofactors of the glycolytic pathway in brain.
      ), indirectly suggesting a normal rate of cerebral energy synthesis. At the onset of coma, cerebral lactate and, where appropriate, cerebral lactate/pyruvate ratios were consistent with normal oxidative metabolism of the brain. Changes in serum osmolarity, pH, glucose, ketone concentrations, or cerebral catecholamines were not responsible for the onset of coma. Average blood octanoate levels at onset of coma were 8 μmoles per milliliter and fell to 3 μmoles per milliliter prior to awakening. Brain octanoate at onset of coma was about 2.6 μmoles per gram, with similar values in the cortex and brainstem. In conclusion, these direct in vivo studies suggest that altered regional cerebral energy metabolism is not responsible for SCFA-induced acute experimental coma.
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