Ammonium chloride and alpha-ketoglutaric acid increase glutamine availability in the early phase of induced acute metabolic acidosis.
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.
Nordgren
A
A
Department of Surgical Sciences/Anesthesiology and Intensive Care, University Hospital, SE-751 85 Uppsala, Sweden.
Karlsson
T
T
Wiklund
L
L
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
D000597:Amino Acids, Branched-Chain; D007656:Ketoglutaric Acids; D000644:Quaternary Ammonium Compounds; D000643:Ammonium Chloride; D005973:Glutamine; D002956:Citrulline; D018698:Glutamic Acid; D014508:Urea