ENTERAL ADMINISTRATION OF ORNITHINE ALPHA-KETOGLUTARATE OR ARGININE ALPHA-KETOGLUTARATE - A COMPARATIVE-STUDY OF THEIR EFFECTS ON GLUTAMINEPOOLS IN BURN-INJURED RATS

Objectives: Ornithine alpha-ketoglutarate has proved to be an efficien t nutritional support in trauma situations, especially after burn inju ry. To determine whether the action of ornithine alpha-ketoglutarate i s due to its alpha-ketoglutarate moiety (as a glutamine precursor), we studied the effects of alpha-ketoglutarate administered to rats as or nithine alpha-ketoglutarate, or in combination with arginine salt (arg inine alpha-ketoglutarate), as the two closely related amino acids hav e similar metabolic behavior. Design: Prospective, randomized trial. S etting: Animal laboratory. Subjects: Forty-six male Wistar rats, weigh ing similar to 90 g. Interventions: Rats were burned over 20% of their body surface area, starved for 24 hrs, with water ad libitum, and the n enterally refed for 48 hrs using Osmolite(R)(210 kcal/kg/day, 1.2 g of nitrogen/kg/day), supplemented with one of the following: a) an amo unt of glycine isonitrogenous to ornithine alpha-ketoglutarate (group 1) b) 5 g of monohydrated ornithine alpha-ketoglutarate/kg/day (group 2); c) an amount of arginine alpha-ketoglutarate isonitrogenous to orn ithine alpha-ketoglutarate (group 3); or d) an amount of arginine alph a-ketoglutarate isomolar to ornithine alpha-ketoglutarate (group 4). M easurements and Main Results: We measured amino acid concentrations in plasma, muscle, and river, and plasma urea concentration. At refeedin g, ornithine alpha-ketoglutarate increased plasma glutamine concentrat ion (p<.05 vs. the three other groups), and counteracted the increase in plasma phenylalanine concentration. In muscle, although the three a lpha-ketoglutarate combinations induced similar increases in the gluta mate pool, ornithine alpha-ketoglutarate induced the highest increase in glutamine (7.0 +/- 0.3 vs. 5.4 +/- 0.3 mu mol/g in group 3, 6.3 +/- 0.3 in group 4, and 4.6 +/- 0.2 in group 1, p<.01 between group 2 and groups 3 or 1). Also, only ornithine alpha-ketoglutarate increased li ver glutamine concentration. Finally, isomolar arginine alpha-ketoglut arate increased plasma urea concentration (+50% vs, the three other gr oups, p<.01). Conclusions: Our results demonstrate, for the first time , the following: a) the action of ornithine alpha-ketoglutarate as a g lutamine precursor cannot solely be ascribed to alpha-ketoglutarate si nce arginine nine alpha-ketoglutarate combinations did not exhibit thi s effect to the same extent; and b) the action of ornithine alpha-keto glutarate is not due to its nitrogen content since isonitrogenous argi nine alpha-ketoglutarate did not reproduce the effects of ornithine al pha-ketoglutarate.