Effect of alpha-ketoglutarate infusions on organ balances of glutamine and glutamate in anaesthetized dogs in the catabolic state.
1. The salt complex of L-(+)-ornithine and alpha-ketoglutarate (2-oxoglutarate) has recently been proposed for the treatment of patients in the catabolic state. As yet, it is unclear which of the two substrates (ornithine or alpha-ketoglutarate) is responsible for the anticatabolic effect. We infused alpha-ketoglutarate into anaesthetized post-operative dogs in order to investigate whether infusion of alpha-ketoglutarate affects the flux of glutamine and glutamate between skeletal muscle and the splanchnic bed. We used three infusion rates: 3, 10 and 20 mumol min-1 kg-1. A steady state of alpha-ketoglutarate concentration in arterial whole-blood was attained only when the infusion rate was 3 mumol min-1 kg-1. 2. Arterial whole-blood concentrations of alpha-ketoglutarate were 8.8 +/- 1.2 mumol/l in the basal period and rose to 208 +/- 41, 344 +/- 61 and 1418 +/- 315 mumol/l after 60 min infusions of alpha-ketoglutarate at 3, 10 and 20 mumol min-1 kg-1, respectively. 3. alpha-Ketoglutarate uptake was measured in skeletal muscle, liver, gut and kidneys in the basal period and during the infusion of alpha-ketoglutarate. The net uptake of infused alpha-ketoglutarate was highest in the skeletal muscle, followed by kidneys, liver and gut. 4. The alpha-ketoglutarate load increased the muscular tissue content of alpha-ketoglutarate from 49.5 +/- 5 to 142 +/- 15 nmol/g of dry substance (P less than 0.001), but did not alter the muscular glutamate or glutamine contents.(ABSTRACT TRUNCATED AT 250 WORDS)
Roth
E
E
1st Department of Surgery, University of Vienna, Austria.
Karner
J
J
Roth-Merten
A
A
Winkler
S
S
Valentini
L
L
Schaupp
K
K
D000818:Animals; D004285:Dogs; D005971:Glutamates / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007656:Ketoglutaric Acids / Q000008:administration & dosage* / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
D005971:Glutamates; D007656:Ketoglutaric Acids; D011506:Proteins; D005973:Glutamine