Effect of α-ketoglutarate infusions on organ balances of glutamine and glutamate in anaesthetized dogs in the catabolic state

Abstract

1. The salt complex of l-(+)-ornithine and α-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 α-ketoglutarate) is responsible for the anticatabolic effect. We infused α-ketoglutarate into anaesthetized postoperative dogs in order to investigate whether infusion of α-ketoglutarate affects the flux of glutamine and glutamate between skeletal muscle and the splanchnic bed. We used three infusion rates: 3, 10 and 20 μmol min−1 kg−1. A steady state of α-ketoglutarate concentration in arterial whole-blood was attained only when the infusion rate was 3 μmol min−1 kg−1. 2. Arterial whole-blood concentrations of α-ketoglutarate were 8.8 ± 1.2 μmol/l in the basal period and rose to 208 ± 41, 344 ± 61 and 1418 ± 315 μmol/l after 60 min infusions of α-ketoglutarate at 3, 10 and 20 μmol min−1 kg−1, respectively. 3. α-Ketoglutarate uptake was measured in skeletal muscle, liver, gut and kidneys in the basal period and during the infusion of α-ketoglutarate. The net uptake of infused α-ketoglutarate was highest in the skeletal muscle, followed by kidneys, liver and gut. 4. The α-ketoglutarate load increased the muscular tissue content of α-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 α-ketoglutarate had no effect on the plasma glutamine concentration, nor on the glutamine and glutamate balances across the skeletal muscle, liver and gut. However, α-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 α-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.