MUSCLE AMMONIA AND GLUTAMINE EXCHANGE DURING CHRONIC LIVER INSUFFICIENCY IN THE RAT

The aim of this study was to investigate the role of skeletal muscle i n ammonia and glutamine metabolism during chronic hyperammonemia induc ed by liver insufficiency. The hindquarter ammonia and amino acid flux es and muscle tissue concentrations were studied in two rat models of chronic liver insufficiency, portacaval shunting and portacaval shunti ng plus bile-duct ligation, as well as in sham-operated animals, 7 and 14 days after surgery, and in normal, unoperated rats. To reduce nutr itional influences, portacaval-shunted rats and sham-operated rats wer e pair-fed to portacaval shunt/biliary obstruction rats. Arterial ammo nia levels were elevated in both liver insufficiency groups. In the po rtacaval shunting plus bile-duct ligation group, arterial glutamine le vels were elevated compared with sham-operated controls. No net hindqu arter ammonia uptake was observed in any of the groups, despite hypera mmonemia in the chronic liver insufficiency groups. Hindquarter glutam ine release was always increased in the liver insufficiency groups com pared with sham-operated controls, despite similar muscle glutamine le vels in the sham-operated and hyperammonemic groups, suggesting enhanc ed muscle glutamine synthesis in the latter groups. Muscle ammonia lev els were always increased and muscle glutamate decreased in the hypera mmonemic groups, probably indicating glutamate consumption by enhanced glutamine synthesis. The increased phenylalanine tissue concentration s and efflux in portacaval shunt/biliary obstruction rats suggest that enhanced net muscle protein breakdown, amino acid catabolism and tran samination, rather than ammonia uptake from the blood furnish amino ac ids and ammonia for enhanced glutamine synthesis. These experiments su ggest that nutritional factors are important-in explaining altered mus cle metabolism during chronic liver insufficiency. (C) Journal of Hepa tology.