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Research Article Free access | 10.1172/JCI105583
Department of Internal Medicine, Liver-Gastrointestinal Unit, The University of Texas Southwestern Medical School at Dallas, Dallas, Texas
†John and Mary R. Markle Scholar in Academic Medicine.
Address requests for reprints to Dr. Steven Schenker, Dept. of Internal Medicine, The University of Texas Southwestern Medical School, Dallas, Texas 75235.
*Submitted for publication November 16, 1966; accepted January 30, 1967.
This study was supported in part by U. S. Public Health Service grant NB 05481-02 from the National Institute of Neurological Diseases and Blindness.
Presented in part at the meetings of the Southern Society for Clinical Investigation, New Orleans, 1966, and The American Society for Clinical Investigation, Atlantic City, 1966.
Find articles by Schenker, S. in: JCI | PubMed | Google Scholar
Department of Internal Medicine, Liver-Gastrointestinal Unit, The University of Texas Southwestern Medical School at Dallas, Dallas, Texas
†John and Mary R. Markle Scholar in Academic Medicine.
Address requests for reprints to Dr. Steven Schenker, Dept. of Internal Medicine, The University of Texas Southwestern Medical School, Dallas, Texas 75235.
*Submitted for publication November 16, 1966; accepted January 30, 1967.
This study was supported in part by U. S. Public Health Service grant NB 05481-02 from the National Institute of Neurological Diseases and Blindness.
Presented in part at the meetings of the Southern Society for Clinical Investigation, New Orleans, 1966, and The American Society for Clinical Investigation, Atlantic City, 1966.
Find articles by McCandless, D. in: JCI | PubMed | Google Scholar
Department of Internal Medicine, Liver-Gastrointestinal Unit, The University of Texas Southwestern Medical School at Dallas, Dallas, Texas
†John and Mary R. Markle Scholar in Academic Medicine.
Address requests for reprints to Dr. Steven Schenker, Dept. of Internal Medicine, The University of Texas Southwestern Medical School, Dallas, Texas 75235.
*Submitted for publication November 16, 1966; accepted January 30, 1967.
This study was supported in part by U. S. Public Health Service grant NB 05481-02 from the National Institute of Neurological Diseases and Blindness.
Presented in part at the meetings of the Southern Society for Clinical Investigation, New Orleans, 1966, and The American Society for Clinical Investigation, Atlantic City, 1966.
Find articles by Brophy, E. in: JCI | PubMed | Google Scholar
Department of Internal Medicine, Liver-Gastrointestinal Unit, The University of Texas Southwestern Medical School at Dallas, Dallas, Texas
†John and Mary R. Markle Scholar in Academic Medicine.
Address requests for reprints to Dr. Steven Schenker, Dept. of Internal Medicine, The University of Texas Southwestern Medical School, Dallas, Texas 75235.
*Submitted for publication November 16, 1966; accepted January 30, 1967.
This study was supported in part by U. S. Public Health Service grant NB 05481-02 from the National Institute of Neurological Diseases and Blindness.
Presented in part at the meetings of the Southern Society for Clinical Investigation, New Orleans, 1966, and The American Society for Clinical Investigation, Atlantic City, 1966.
Find articles by Lewis, M. in: JCI | PubMed | Google Scholar
Published May 1, 1967 - More info
Interference with cerebral energy metabolism due to excess ammonia has been postulated as a cause of hepatic encephalopathy. Furthermore, consideration of the neurologic basis of such features of hepatic encephalopathy as asterixis, decerebrate rigidity, hyperpnea, and coma suggests a malfunction of structures in the base of the brain and their cortical connections.
The three major sources of intracerebral energy, adenosine triphosphate (ATP), phosphocreatine, and glucose, as well as glycogen, were assayed in brain cortex and base of rats given ammonium acetate with resultant drowsiness at 5 minutes and subsequent coma lasting at least 30 minutes.
Cortical ATP and phosphocreatine remained unaltered during induction of coma. By contrast, basilar ATP, initially 1.28 ± 0.15 μmoles per g, was unchanged at 2.5 minutes but fell by 28.1, 27.3, and 26.6% (p < 0.001) at 5, 15, and 30 minutes after NH4Ac. At comparable times, basilar phosphocreatine fell more strikingly by 62.2, 96, 77.1, and 71.6% (p < 0.001) from a control level of 1.02 ± 0.38 μmoles per g. These basilar changes could not be induced by anesthesia, psychomotor stimulation, or moderate hypoxia and were not due to increased accumulation of ammonia in the base. Glucose and glycogen concentrations in both cortex and base fell significantly but comparably during development of stupor, and prevention of the cerebral glucose decline by pretreatment with glucose did not obviate ammonia-induced coma or the basilar ATP fall.
These findings represent the first direct evidence that toxic doses of ammonia in vivo acutely affect cerebral energy metabolism and that this effect is preferentially localized to the base of the brain.
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