Hepatic encephalopathy experimental

The relationship between drug concentration and response also can be altered in patients with advanced liver disease. Of greatest concern is the fact that customary doses of sedatives may precipitate the disorientation and coma that are characteristic of portal-systemic or hepatic encephalopathy. Experimental hepatic encephalopathy is associated with increased y-aminobutyric acid-mediated inhibitory neurotransmission, and there has been some success in using the benzodiazepine antagonist flumazenil to reverse this syndrome (50). This provides a theoretical basis for the finding that brain hypersensitivity, as well as impaired drug elimination, is responsible for the exaggerated sedative response to diazepam that is exhibited by some patients with chronic liver disease (51). Bakti et al. (52) conducted a particularly well-controlled... 

Moroni F, Lombardi G, Moneti G, Cortesini C The release and neosynthesis of glutamic acid are increased in experimental models of hepatic encephalopathy. J Neurochem 1983 40 850-854. 

Baraldi M, Zeneroli ML Experimental hepatic encephalopathy Changes in the binding of gamma-aminobutyric acid. Science 1982 216 427-429. 

Basile AS, Gammal SH, Jones EA, Skolnick P GABA-A receptor complex in an experimental model of hepatic encephalopathy Evidence for elevated levels of an endogenous benzodiazepine receptor complex ligand. J Neurochem 1989 53 1057-1063. 

Many of the neuropsychiatric symptoms in early hepatic encephalopathy, such as altered sleep patterns, are signs that have classically been attributed to modifications of serotoninergic neurotransmission. Serotonin turnover, as indicated by the ratio of the concentrations of the metabolite 5-hydroxyindoleacetic acid to serotonin, is increased in brain in both human and experimental hepatic encephalopathy. 

Baraldi, M., Caselgrandi, E., Borella, P., Zeneroli, M.L. Decrease of brain zinc in experimental hepatic encephalopathy. Brain Res. 1983 258 170-172... 

Although furosemide is very hepatotoxic in experimental animals, only a few cases of jaundice have been reported (SED-8, 484) (SED-8, 485), and no fully documented cases have so far been published. However, in patients with cirrhosis furosemide readily precipitates hepatic encephalopathy (SED-8, 485), even when low doses are used (1). 

Moroni F, Lombardi G, Carla V, Pellegrini D, Carassale GL, Cortesini C. Content of quinolinic acid and other tryptophan metabolites increases in brain regions of rats used as experimental models of hepatic encephalopathy. J. Neurochem., 46, 869-874, 1986a Moroni F, Lombardi G, Carla V, Lai S, Etienne P, Neiir NPV. Increase in the content of quinolinic acid in cerebrospinal fluid and frontal cortex of patients with hepatic failure. J. Neurochem., 47, 1667-1671, 1986b... 

Bergqvist, P.B., Hjorth, S., Audet, R.M., Apelqvist, G., Bengtsson, R, and Butterworth, R.R 1996. Ammonium acetate challenge in experimental chronic hepatic encephalopathy induces a transient increase of brain 5-HT release in vivo. Eur. Neuropsychopharmacol. 6 317-322. 

A study by Rao et al." measured the levels of amino acids using in vivo cerebral microdialysis in the frontal cortex of portacaval-shunted rats administered ammonium acetate to precipitate severe portal-systemic encephalopathy. In comparison to sham-operated control rats, tryptophan levels increased by 63% along with those of other amino acids. However, the experimental animals did not have a significant increase in extracellular fluid concentration of tryptophan, suggesting that increased spontaneous release of tryptophan in cerebral cortex is not implicated in the pathogenesis of hepatic coma. 

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