title: Ammonium chloride and alpha-ketoglutaric acid increase glutamine availability in the early phase of induced acute metabolic acidosis.
abstract: BACKGROUND
  Glutamine deficiency in critical illness is associated with increased morbidity and mortality. We hypothesized that ammonium chloride (NH(4)Cl) and alpha-ketoglutaric acid (alpha-KGA) infusions could increase glutamine availability possibly through de novo synthesis in the liver.
  
  
  METHODS
  Anesthetized post-absorptive pigs were allocated to four groups (n = 8). The study groups received either a 4-h intravenous infusion of alpha-KGA, 11.4 micromol/kg/min and NH(4) (+), 9.7 micromol/kg/min (group 1), or alpha-KGA, 2.85 micromol/kg/min and NH(4) (+), 46.3 micromol/kg/min (group 2), or alpha-KGA, 11.4 micromol/kg/min (group 3), or isotonic saline (control group). Plasma concentrations of glutamine and glutamine exchange in liver, intestine and skeletal muscle were investigated.
  
  
  RESULTS
  Plasma glutamine concentrations in group 1 (58% increase) were greater (P < 0.05) compared with the control group (14% decrease) and group 3 (13% decrease), and in group 2 (91% increase) compared with the control group, group 3 (P < 0.0001) and group 1 (P < 0.05). Intestinal glutamine extractions in group 2 were significantly greater (P < 0.01) compared with all other groups. Neither the liver nor the hind leg increased its release of glutamine. Arterial pH decreased (all P < 0.001) to 7.39 +/- 0.01 in the control group, 7.30 +/- 0.01 in group 1, 7.19 +/- 0.01 in group 2 and 7.35 +/- 0.01 in group 3.
  
  
  CONCLUSIONS
  Infusions of alpha-KGA and NH(4)Cl, to a pH range of 7.20-7.30, did not enhance hind leg or hepatic glutamine release. The increased plasma concentrations of glutamine were effects of NH(4)Cl, not alpha-KGA, and caused either by de novo synthesis or decreased degradation.
authors.affiliation: Department of Surgical Sciences/Anesthesiology and Intensive Care, University Hospital, SE-751 85 Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Nordgren
authors.forename: T
authors.initials: T
authors.lastname: Karlsson
authors.forename: L
authors.initials: L
authors.lastname: Wiklund
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000208:Acute Disease; D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D002956:Citrulline / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000097:blood / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D034421:Sus scrofa; D014508:Urea / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D007656:Ketoglutaric Acids; D000644:Quaternary Ammonium Compounds; D000643:Ammonium Chloride; D005973:Glutamine; D002956:Citrulline; D018698:Glutamic Acid; D014508:Urea