title: Interorgan ammonia, glutamate, and glutamine trafficking in pigs with acute liver failure.
abstract: Ammonia reduction is the target for therapy of hepatic encephalopathy, but lack of quantitative data about how the individual organs handle ammonia limits our ability to develop novel therapeutic strategies. The study aims were to evaluate interorgan ammonia metabolism quantitatively in a devascularized pig model of acute liver failure (ALF). Ammonia and amino acid fluxes were measured across the portal drained viscera (PDV), kidneys, hind leg, and lungs in ALF pigs. ALF pigs developed hyperammonemia and increased glutamine levels, whereas 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, whereas muscle took up ammonia. Data suggest that the lungs are able to remove ammonia from the circulation during the initial stage of ALF. Our study provides new data supporting the concept 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.
authors.affiliation: Liver Failure Group, Institute of Hepatology, Univ. College London, 69-75 Chenies Mews, London WC1E 6HX, UK.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Ytrebø
authors.forename: Sambit
authors.initials: S
authors.lastname: Sen
authors.forename: Christopher
authors.initials: C
authors.lastname: Rose
authors.forename: Gabrie A M
authors.initials: GA
authors.lastname: Ten Have
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Davies
authors.forename: Stephen
authors.initials: S
authors.lastname: Hodges
authors.forename: Geir I
authors.initials: GI
authors.lastname: Nedredal
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
authors.forename: Roger
authors.initials: R
authors.lastname: Williams
authors.forename: Arthur
authors.initials: A
authors.lastname: Revhaug
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
authors.forename: Nicolaas E P
authors.initials: NE
authors.lastname: Deutz
mesh_terms: D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D022124:Hyperammonemia / Q000209:etiology / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000150:complications / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D009928:Organ Specificity; D013552:Swine; D014018:Tissue Distribution
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D000641:Ammonia