Interorgan ammonia, glutamate and glutamine trafficking in pigs with acute liver failure

Background/Aims: Ammonia reduction is the target for therapy of hepatic encephalopathy (HE) but lack of quantitative data about how the individual organs handle ammonia limit our ability to develop novel therapeutic strategies. The study aims were to evaluate interorgan ammonia metabolism quantitatively in a devascularised pig model of acute liver failure (ALF). Methods: Ammonia and amino acid fluxes were measured across the portal drained viscera (PDV), kidneys, hind-leg, and lungs in ALF pigs. Results: ALF pigs developed hyperammonemia and increased glutamine levels, while glutamate levels were decreased. PDV contributed to the hyperammonemic state mainly through increased shunting and not as a result of increased glutamine breakdown. The kidneys were quantitatively as important as PDV in systemic ammonia release, while muscle took up ammonia. Data suggest that the lungs are able to remove ammonia from the circulation during the initial stage of ALF. Conclusions: Our study provides the novel observation of glutamate deficiency in a pig model of ALF. Furthermore, the kidneys are quantitatively as important as PDV in ammonia production and the muscles play an important role in ammonia removal. AD - Digestive Surgery, University Hospital Northern Norway, Norway. AU - Ytrebo LM AU - Sen S AU - Rose C AU - Ten Have GA AU - Davies NA AU - Hodges S AU - Nedredal GI AU - Romero-Gomez M AU - Williams R AU - Revhaug A AU - Jalan R AU - Deutz NE LA - ENG PT - JOURNAL ARTICLE DEP - 20060615 TA - Am J Physiol Gastrointest Liver Physiol JID - 100901227