Acute hepatic failure is associated with many biochemical abnormalities in plasma and brain . Changes that correlate well with the degree of behavioral impairment may be important factors in the development of encephalopathy . We measured the concentrations of intermediary metabolites, ammonia, and amino acids in brain and plasma and the rate of whole-brain glucose utilization in rats with an acutely devascularized liver . In all rats an estimate of the grade of encephalopathy (reflected by behavioral impairment) was made . Rats underwent portacaval shunting and hepatic artery ligation (or sham operation) and were kept normoglycemic and normothermic thereafter . We sampled blood and whole brain (by near-instantaneous freeze-blowing) 2, 4, or 6 h later. There were no alterations in levels of high-energy phosphate metabolites in the brain or in metabolites associated with the glycolytic pathway and Krebs cycle, except lactate and pyruvate . Brain glucose use was decreased similarly at all times after surgery. Levels of ammonia and many amino acids were increased in brain and plasma ; brain aspartate, glutamate, and arginine levels were decreased . The increases in content of plasma ammonia and brain glutamine, proline, alanine, and aromatic amino acids and the decreases in brain aspartate and glutamate were most strongly correlated with behavioral impairment .

Disturbances in brain monoamine neurotransmitter metabolism have been implicated in the development of hepatic encephalopathy produced by portacaval shunting or liver disease. We have measured the content of serotonin, norepinephrine and dopamine, as well as their metabolites 5-hydroxyindoleacetic acid, dihydroxyphenylacetic acid and homovanillic acid in nine selected brain areas of rats with portacaval shunts and sham-operated control rats. All substances were measured in single samples using high performance liquid chromatography with electrochemical detection, after a simple extraction procedure. In shunted rats serotonin content was 26% higher in the raphe nuclei area, and 5-hydroxyindoleacetic acid throughout the brain (by 51 to 137%), suggesting increased serotonin turnover. Norepinephrine content was higher by 26% in the frontal cortex. Dopamine content was unaffected; however its metabolites were higher in a few areas including the caudate and ventral tegmentum. Brain content of the monoamine precursor amino acids tryptophan, tyrosine and phenylalanine was higher throughout the brain in the shunted rats. The results suggest that serotonin metabolism is altered throughout the brain after portacaval shunting, which could be related to some of the characteristic behavioral abnormalities found in this condition. Catecholamine metabolism appears to be more selectively and less extensively affected.