Hepatic encephalopathy: Application of visual evoked responses to test hypotheses of its pathogenesis in rats

Abstract

A previous study of the patterns of visual evoked responses (VERs) in rats was interpreted as providing support for the synergistic neurotoxins hypothesis of the pathogenesis of hepatic encephalopathy (HE) due to fulminant hepatic failure (FHF). In contrast, other studies of the patterns of VERs in rabbits with different encephalopathies were interpreted as providing support for the concept that increased GABA-ergic tone may contribute to the neural inhibition of HE due to FHF. To attempt to resolve the discordant findings in these studies, additional studies of VERs have been undertaken in rats. To induce increased tissue levels of ammonia, mercaptans and fatty acids which are found in HE due to FHF, carefully predetermined doses of urease, dimethyldisulphide and octanoic acid were administered. The (pre-seizure) encephalopathy induced by these three agents was associated with abnormalities of the VER waveform that were fundamentally different from the abnormalities of the VER waveform associated with HE due to thioacetamide-induced FHF. However, the VER waveform in this model of HE due to FHF resembled closely that associated with pentobarbital-induced encephalopathy. These findings are in satisfactory agreement with those in the previous analogous studies in rabbits. They do not provide support for the synergistic neurotoxins hypothesis of the pathogenesis of HE, but are entirely consistent with increased GABA-ergic tone contributing to the neural inhibition of HE due to FHF.