EFFECT OF ALPHA-KETOGLUTARATE INFUSIONS ON ORGAN BALANCES OF GLUTAMINE AND GLUTAMATE IN ANESTHETIZED 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-mu-mol min-1 kg-1. A steady state of alpha-ketoglutarate concentration in arterial whole-blood was attained only when the infusion rate was 3-mu-mol min-1 kg-1. 2. Arterial whole-blood concentrations of alpha-ketoglutarate were 8.8 +/- 1.2-mu-mol/l in the basal period and rose to 208 +/- 41, 344 +/- 61 and 1418 +/- 315-mu-mol/l after 60 min infusions of alpha-ketoglutarate at 3, 10 and 20-mu-mol 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 < 0.001), but did not alter the muscular glutamate or glutamine contents. 5. Infusion of alpha-ketoglutarate had no effect on the plasma glutamine concentration, nor on the glutamine and glutamate balances across the skeletal muscle, liver and gut. However, alpha-ketoglutarate infusion significantly reduced the renal extraction of glutamine (P < 0.05) and enhanced the renal production of glutamate (P < 0.05). 6. We conclude that an intravenous alpha-ketoglutarate load affects the renal balances of glutamine and glutamate, but does not alter the nitrogen flux of glutamine and glutamate between skeletal muscle, liver and gut.