[Pathogenesis of hepatic encephalopathy--studies in the rabbit model of acute liver failure]

Abstract

In rabbits the administration of neither ammonia, nor a mixture of ammonia, a mercaptan and a fatty acid reproduces the changes in visual evoked potentials that occur in galactosamine-induced hepatic coma. The abnormal pattern of visual evoked potentials in galactosamine-induced hepatic coma can be reproduced by administering drugs which induce activation of the gamma-aminobutyric acid (GABA) neurotransmitter system. Also in rabbits the administration of ammonia does not reproduce the changes in receptors for glutamate and GABA in the brain that occur in galactosamine-induced hepatic coma. Galactosamine-induced hepatic coma is not associated with any functionally significant changes in the molecular components of the postsynaptic dopamine receptor. These findings provide no support for the hypotheses of the pathogenesis of hepatic encephalopathy that implicate ammonia, the synergistic action of ammonia, mercaptans and fatty acids or false neurotransmitters. However, these findings are entirely consistent with activation of the GABA neurotransmitter system contributing to neural inhibition in hepatic encephalopathy.