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Abstract #1034

Improvement of Ammonia Removal by Glutamine Synthesis Is Associated with Attenuation of Encephalopathy in Acute Liver Failure: Protective Effects of the NMDA Receptor Antagonist Memantine

Jessica Heins1,2, Weinlei Jiang2, Sven Gottschalk2, Dieter Leibfritz1, Roger F. Butterworth2, Claudia Zwingmann1,2

1Department of Organic Chemistry, University of Bremen, Bremen, Germany; 2Centre de Recherche, Hospital Saint-Luc, Montreal, Quebec, Canada

Hyperammonemia is a key factor leading to neurological dysfunction in acute hepatic encephalopathy (HE). Recent evidence suggests a limited capacity of brain glutamine synthetase, the major detoxification mechanism for ammonia. Our aim was to determine in rats with HE whether prevention of ammonia-induced NMDA receptor overactivation is related to increased glutamine synthesis and attenuation of encephalopathy. 1H-, and 13C-NMR was used to measure brain metabolites following administration of [U-13C]glucose to rats with end-to-side portacaval anastomosis followed by hepatic artery ligation. The data demonstrate that memantine delays the time to coma, decreased blood ammonia and improves cerebral glutamine synthesis in HE.