Nitrogen sparing effect of Ornicetil in the immediate postoperative state clinical biochemistry and nitrogen balance

The salt complex of alpha-ketoglutarate and ornithine, L(+)ornithine alpha-ketoglutarate - ORNICETIL (OR) - is able to bind six amino groups per molecule without enzymatic intervention. The present study was undertaken to determine whether intravenous administration of OR together with total parenteral nutrition (TPN) has a beneficial effect on nitrogen utilization in the immediate postoperative phase. Thirteen patients were investigated after major abdominal operations (resection of colon or rectum). All patients received TPN for 5 days postoperatively. Energy (165 kJ/kg BW) was given as fat (Intralipid 20%) and carbohydrate (Glucose 20%). Seven patients (controls) received 0.15 g amino acid (AA)-N/kg BW (Vamin). Six patients had an isonitrogenous regimen but with 2.5 g AA-N being replaced by Ornicetil (OR group). The excretion of urea, creatinine, ammonia, 3-methyl-histidine (3-MeHis) and total-N was determined throughout the study and the daily nitrogen balance was calculated. Blood samples were drawn serially before and after surgery for routine clinical biochemistry. The day-to-day nitrogen balance was significantly better when OR was given. Urea excretion was significantly reduced, and the urinary ammonia losses in the OR group were one third of those in the control group. In the control group 3-MeHis correlated negatively with the nitrogen balance. The regression line obtained, y = 265 - 21.6 x (p < 001), and the calculated correlation coefficient, r = 0.87 (p < 0.001), were highly significant. In contrast, no correlation could be demonstrated between 3-MeHis output and nitrogen balance in the OR group (r = 0.18, N.S.). The results indicate better postoperative nitrogen economy in the OR group than in the control group. Stimulation of insulin and growth hormone secretion may be contributing factors in the better nitrogen utilization. The increased ammonia excretion postoperatively in the control group was completely abolished when OR was given simultaneously with decreased urea formation, suggesting a product inhibition of arginase in the liver cytosol and also indicating that amino groups generated by the enhanced gluconeogenesis were trapped by OR owing to stimulated transamination in peripheral muscle tissues. The significant negative correlation between 3-MeHis excretion and nitrogen balance in the control group strongly indicates a correlation between net protein catabolism and increased postoperative muscle protein breakdown. In contrast, the total absence of correlation between nitrogen balance and 3-MeHis excretion in the OR group suggests a diminished (or zero) net muscle protein breakdown.