Effects of etomidate on free intracellular amino acid concentrations in polymorphonuclear leucocytes in vitro

Background: Previous studies have shown the inhibitory effects of etomidate on polymorphonuclear leucocyte (PMN) function. No reports exist, however, regarding free intracellular amino acid metabolism, although physiological cell metabolism and basic cell functions rely upon a balanced intracellular amino acid content and the cell membrane-mediated separation of cellular a mino acids from the extracellular plasma amino acid pool. Thus, in the curr ent study, we evaluated the effects of etomidate on free intracellular amin o acid metabolism in PMN. Methods: With ethics committee approval, blood was withdrawn from 35 health y volunteers and incubated (1 h) either with 0 mu g/ml, 0.0156 mu g/ml, 0.0 625 mu g/ml or 0.5 mu g/ml of etomidate as well as with its additives (prop ylene glycol and Lipofundin MCT(R) 10%). The PMN were separated using stand ardized Percoll(R)-gradient and centrifugation procedure before deep-freezi ng and lyophilization techniques were employed. All PMN samples were dissol ved in methanol/H2O, and the concentrations of free intracellular amino aci ds were monitored using both novel advanced PMN-separation and high-perform ance liquid chromatography techniques. Results: Etomidate influenced important free amino acid profiles in PMN in a dose-dependent manner, indicating complex changes of cellular amino acid turnover. Neither propylene glycol nor Lipofundin MCT(R) 10% changed free a mino acid concentrations in PMN. Conclusions: For the first time, the effects of etomidate on free intracell ular amino acid metabolism in PMN have been investigated. Our results draw attention to the biochemical pathways which may be involved in etomidate-in duced alterations in PMN function and cellular immunocompetence. (C) Acta Anaesthesiologica Scandinavica 44 (2000).