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

BACKGROUND AND OBJECTIVE

The objective of this study was to determine the dose as well as the duration of exposure-dependent effects of methohexital on neutrophil [polymorphonuclear leucocyte (PMN)] free amino acid profiles and, in a parallel study, on PMN immune functions.

METHODS

Whole blood samples were taken from 20 volunteers and incubated with methohexital [0 (control), 3.6, 26, 130 and 260 microg mL-1] for 10, 30, 60 or 120 min. PMN amino acid profiles were documented using advanced PMN separation and high-performance liquid chromatography procedures. Superoxide anion (O2-) and hydrogen peroxide production (H2O2), and activity of released myeloperoxidase (MPO), were determined photometrically.

RESULTS

After methohexital, significant dose (> or = 26 microg mL-1) as well as duration of exposure-dependent (> or = 30 min) increases in histidine, isoleucine, leucine, valine, methionine, serine, glycine, threonine, and decreases in glutamine, glutamate, aspartate, asparagine, arginine, ornithine, citrulline, alanine and taurine were observed (P < or = 0.05). Concerning PMN immune functions, methohexital significantly decreased O2-, H2O2 formation and MPO (> or = 26 microg mL-1, > or = 30 min, P < or = 0.05).

CONCLUSIONS

Altogether, there is significant relevance to the pharmacological regimens which enhance the supply of methohexital in whole blood. In regards to our results, we suggest that considerable changes in PMN 'dynamic free amino acid pool', for example induced by methohexital, may be one of the determinants in cell nutrition adversely affecting PMN metabolism. It is partially through its effect on the PMN free amino acid pool that maleficent pharmacological stress may have an unintentional influence on PMN immune functions.