Effects of systemic prostaglandin E1 on hepatic amino acid-nitrogen metabolism in patients with cirrhosis.
Prostaglandins of the E (PGE) series have long been considered "catabolic" hormones, but recent data suggest that they may be secreted in critically ill patients to counteract stress hormones, stimulating protein synthesis. Their use is under scrutiny to improve hepatic microcirculation and as cytoprotective agents. We tested the effects of PGE1 on hepatic and whole-body nitrogen metabolism in eight patients with cirrhosis. Urea-nitrogen synthesis rate, alpha-amino-nitrogen levels, and nitrogen exchange were measured in the basal, postabsorptive state and in response to continuous alanine infusion, in paired experiments, during superinfusion of PGE1 or saline. Splanchnic and systemic hemodynamics were assessed by echo-Doppler at the beginning and at the end of each experiment. PGE1 produced a rapid fall in plasma amino acids and in urea-nitrogen synthesis rate, as well as a positive nitrogen exchange. The slope of the regression of alpha-amino-nitrogen levels on urea-nitrogen synthesis rate, a measure of liver cell metabolic activity, was not affected, but the regression line was shifted rightward, suggesting a nitrogen-sparing effect of PGE1. Mesenteric artery and portal flow were unchanged, whereas femoral artery flow increased by 30%. Insulin and glucagon levels were not systematically different. We conclude that PGE1 reduces hepatic urea synthesis rate, independent of hormones and/or hepatic flow, possibly acting at the peripheral level on amino acid transport, thus reducing amino acid supply to the liver. The resulting net nitrogen sparing might be the basis for the beneficial effect of PGE1 in clinical hepatology.
Fabbri
A
A
Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, Università di Bologna, Policlinico S. Orsola, Italy.
Bianchi
G
G
Brizi
M
M
Bugianesi
E
E
Magalotti
D
D
Zoli
M
M
Marchesini
G
G
D000368:Aged; D000527:Alprostadil / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009584:Nitrogen / Q000378:metabolism*; D014508:Urea / Q000378:metabolism
D000596:Amino Acids; D014508:Urea; D000527:Alprostadil; D009584:Nitrogen