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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 (
23.), 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.
- 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.
J. Biol. Chem. 1964; 239: 18
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Accepted: July 13, 1970
Received: February 6, 1970
☆These studies were supported by United States Public Health Grants NB-05841 and MH 17363, and were presented at the Annual Meeting of the American Association for the Study of Liver Diseases, Chicago, Ill., October, 1969.
© 1970 Published by Elsevier Inc.