Isoleucine infusion during "simulated" upper gastrointestinal bleeding improves liver and muscle protein synthesis in cirrhotic patients.
Upper gastrointestinal (GI) bleeding in cirrhotic patients has a high incidence of mortality and morbidity. Postbleeding catabolism has been hypothesized to be partly due to the low biological value of hemoglobin, which lacks the essential amino acid isoleucine. The aims were to study the metabolic consequences of a "simulated" upper GI bleed in patients with cirrhosis of the liver and the effects of intravenous infusion of isoleucine. Portal drained viscera, liver, muscle, and kidney protein kinetics were quantified using a multicatheterization technique during routine portography. Sixteen overnight-fasted, metabolically stable patients who received an intragastric infusion of an amino acid solution mimicking hemoglobin every 4 hours were randomized to saline or isoleucine infusion and received a mixture of stable isotopes (L-[ring-2H5]phenylalanine, L-[ring-2H4]tyrosine, and L-[ring-2H2]tyrosine) to determine organ protein kinetics. This simulated bleed resulted in hypoisoleucinemia that was attenuated by isoleucine infusion. Isoleucine infusion during the bleed resulted in a positive net balance of phenylalanine across liver and muscle, whereas renal and portal drained viscera protein kinetics were unaffected. In the control group, no significant effect was shown.


CONCLUSIONS
The present study investigated hepatic and portal drained viscera protein metabolism selectively in humans. The data show that hepatic and muscle protein synthesis is stimulated by improving the amino acid composition of the upper GI bleed by simultaneous intravenous isoleucine administration.
Olde Damink
Steven W M
SW
Department of Surgery, Academic Hospital, Maastricht University, Maastricht, The Netherlands.
Jalan
Rajiv
R
Deutz
Nicolaas E P
NE
Dejong
Cornelis H C
CH
Redhead
Doris N
DN
Hynd
Paula
P
Hayes
Peter C
PC
Soeters
Peter B
PB
D000328:Adult; D000596:Amino Acids / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D007532:Isoleucine / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism
D000596:Amino Acids; D009124:Muscle Proteins; D011506:Proteins; D007532:Isoleucine