title: Protein synthesis is severely diminished following a simulated upper GI bleed in patients with cirrhosis.
abstract: OBJECTIVE
  An upper gastrointestinal (GI) bleed in cirrhotic patients has been hypothesised to induce catabolism due to the absence of the essential branched chain amino acid (BCAA) isoleucine and an abundance of the BCAA leucine in haemoglobin. We tested whether an upper GI bleed produces hypoisoleucinemia via BCAA antagonism and impairs protein synthesis.
  
  
  METHODS
  Isoleucine turnover and oxidation was studied in 5 metabolically stable patients with cirrhosis during a 4-h period of intragastric saline infusion followed by a 4-h period in which an upper GI bleed was simulated by an amino acid solution mimicking haemoglobin.
  
  
  RESULTS
  The simulated upper GI bleed induced hypoisoleucinemia (26% of initial values) and an increase in leucine (400%) and valine (350%) concentrations. Isoleucine flux and isoleucine oxidation decreased to a third of initial values following a simulated bleed, but the fraction of isoleucine flux used for oxidation did not change. Consequently, the non-oxidative portion of isoleucine flux, representing protein synthesis, decreased similarly.
  
  
  CONCLUSIONS
  The present study shows that a simulated upper GI bleed induces hypoisoleucinemia and decreases protein synthesis markedly. The fact that the percentage of isoleucine flux that was oxidized was not influenced by the hypoisoleucinemic state can only be explained by BCAA antagonism.
authors.affiliation: Department of Surgery, University Hospital Maastricht, Maastricht, The Netherlands. steven.oldedanmink@ah.unimaas.nl
authors.forename: Steven W M
authors.initials: SW
authors.lastname: Olde Damink
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
authors.forename: Nicolaas E P
authors.initials: NE
authors.lastname: Deutz
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hayes
authors.forename: Peter B
authors.initials: PB
authors.lastname: Soeters
mesh_terms: D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism*; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis
chemical_list: D000597:Amino Acids, Branched-Chain; D007532:Isoleucine