Interorgan ammonia, glutamate, and glutamine trafficking in pigs with acute liver failure.
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.
Ytrebø
Lars M
LM
Liver Failure Group, Institute of Hepatology, Univ. College London, 69-75 Chenies Mews, London WC1E 6HX, UK.
Sen
Sambit
S
Rose
Christopher
C
Ten Have
Gabrie A M
GA
Davies
Nathan A
NA
Hodges
Stephen
S
Nedredal
Geir I
GI
Romero-Gomez
Manuel
M
Williams
Roger
R
Revhaug
Arthur
A
Jalan
Rajiv
R
Deutz
Nicolaas E P
NE
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
D005973:Glutamine; D018698:Glutamic Acid; D000641:Ammonia