L-Ornithine vs. L-ornithine-L-aspartate as a treatment for hyperammonemia-induced encephalopathy in rats

Background/Aims: The effect of L-ornithine (ORN) and L-ornithine-L-aspartate (OA) therapy on “extracerebral” nitrogen metabolism, brain metabolism and neurotransmission has been investigated in portacaval shunted rats with hyperammonemia-induced encephalopathy. Methods: One day before ammonium-acetate infusion, a portacaval shunt was performed in three experimental groups: 1 - control rats, 2 - ORN-treated rats and 3 - OA-treated rats. Ammoniumacetate was given as an intravenous bolus injection (0.4 mmolkg bw-‘) followed by a constant infusion (1.9 mmolkg bw-‘.h-‘) so that steady-state blood ammonia concentrations (5oo-800 PM) were obtained in the course of 5 h. After 1 h, ammoniumacetate infusion, either L-ornithine or L-ornithineL-aspartate, was infused for the next 4 h (3.0 mmolkg bw-‘.h-‘) in the treated groups. The following parameters were measured: clinical grade of encephalopathy, EEG activity (n=lO-20/ group), amino acids in plasma (n=lO-20/group) and brain dialysate (n=59/group), and brain metabolites obtained by in viva cerebral ‘H-MRS (n=4-6/group). Results: ORN and OA treatment resulted in significantly lower blood (34% and 39%) and brain