Methohexital affects neutrophil (PMN) dynamic free amino acid peel and immune functions in vitro

Background and objective The objective of this study was to determine the d ose as well as the duration of exposure-dependent effects of methohexital o n neutrophil [polymorphonuclear leucocyte (PMN)] free amino acid profiles a nd, in a parallel study, on PMN immune functions. Methods Whole blood samples were taken from 20 volunteers and incubated wit h methohexital [0 (control), 3.6, 26, 130 and 260 mug mL(-1)] for 10, 30, 6 0 or 120 min. PMN amino acid profiles were documented using advanced PMN se paration and highperformance liquid chromatography procedures. Superoxide a nion (O-2(-)) and hydrogen peroxide production (H2O2) and activity of relea sed myeloperoxidase (MPO), were determined photometrically. Results After methohexital, significant dose (greater than or equal to 26 m ug mL(-1)) as well as duration of exposure-dependent (greater than or equal to 30min) increases in histidine, isoleucine, leucine, valine, methionine, serine, glycine, threonine, and decreases in glutamine, glutamate, asparta te, asparagine, arginine, ornithine, citrulline, alanine and taurine were o bserved (P less than or equal to0.05). Concerning PMN immune functions, met hohexital significantly decreased O-2(-) H2O2 formation and MPO (greater th an or equal to 26 mu gmL(-1), greater than or equal to 30 min, P less than or equal to0.05). Conclusions Altogether, there is significant relevance to the pharmacologic al regimens which enhance the supply of methohexital in whole blood. In reg ards to our results, we suggest that considerable changes in PMN 'dynamic f ree amino acid pool', for example induced by methohexital, may be one of th e determinants in cell nutrition adversely affecting PMN metabolism. It is partially through its effect on the PMN free amino acid pool that maleficen t pharmacological stress may have an unintentional influence on PMN immune functions.