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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 (
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.To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
July 13,
1970
Received:
February 6,
1970
Footnotes
☆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.
Identification
Copyright
© 1970 Published by Elsevier Inc.