Do barbiturates impair zymosan-induced granulocyte function?

PURPOSE: The dose-response relationship of commercially available preparations of methohexital, pentobarbital, phenobarbital, and thiopental and their respective drug-free solutions on granulocyte function was investigated to evaluate whether suppression of neutrophil chemiluminescence is mediated by the barbiturates themselves or by their drug-free solutions. Furthermore, it was assessed whether suppression of chemiluminescence is due to an interaction mainly with neutrophils or to free radical scavenging. METHODS: The dose-response effects of the four barbiturates on granulocyte function were tested by zymosan-induced neutrophil chemiluminescence and, in addition, in a cell-free chemiluminescence system. RESULTS: Methohexital and pentobarbital did not influence zymosan-induced neutrophil chemiluminescence, whereas phenobarbital and thiopental decreased neutrophil chemiluminescence in a dose-dependent fashion. Nonphysiological osmolality (531 mosmol/kg) caused this impaired neutrophil chemiluminescence at the greatest concentration of phenobarbital. Thiopental solely suppressed neutrophil chemiluminescence drug specifically. Because thiopental also reduced chemiluminescence generated in a cell-free system, free radical scavenging might contribute to the impaired neutrophil chemiluminescence observed with thiopental. CONCLUSIONS: With the exception of thiopental, barbiturates do not impair oxygen radical production during phagocytosis of neutrophils.

Do etomidate and propofol influence oxygen radical production of neutrophils?

The effects of etomidate in an alcoholic vehicle and in a lipid-emulsion as well as those of propofol on N-formyl-methionyl-leucyl-phenylalanine (FMLP-) and zymosan-induced oxygen radical production of neutrophils were examined and compared with the effects of their respective vehicles. Furthermore free-radical scavenging capacities of these medications were investigated. The dose-response effects of etomidate, propofol and their respective vehicles on neutrophil function were tested by FMLP- and zymosan-induced chemiluminescence of neutrophils and, in addition, in a cell-free chemiluminescence system. Effects of commercial preparations of etomidate were generally not drug-specific but due to the vehicles and/or to unphysiologic osmolality values. Propofol impaired chemiluminescence of neutrophils in a drug-specific manner, even in the therapeutic concentration range. Free-radical scavenging contributed to this depression of chemiluminescence of neutrophils by propofol. Different composition of the lipid-emulsions of etomidate and propofol resulted in either a stimulation or suppression of chemiluminescence of neutrophils. Propofol but not etomidate impairs chemiluminescence of neutrophils drug-specifically. Besides a potential interaction with the neutrophils, free-radical scavenging accounts for this suppression.

Stereoselective suppression of neutrophil function by ketamine?

The effects of the commercially available ketamine preparation (Ketanest), the ketamine racemate and of the two enantiomers, the R(-)-racemate and the S(+)-racemate, as well as its drug-free solvent were examined by N-formyl-methionyl-leucyl-phenylalanine-(FMLP)- and zymosan-induced oxygen radical production of polymorphonuclear cells (PMN). The racemate and the two enantiomers of ketamine suppressed FMLP- and zymosan-induced chemiluminescence of PMN in a dose-dependent fashion to the same extent. Therefore suppression of chemiluminescence of PMN by ketamine does not result from a specific receptor interaction.

Do barbiturates and their solutions suppress FMLP-induced neutrophil chemiluminescence?

The dose-response relationship of four commercially available barbiturates (methohexitone, pentobarbitone, phenobarbitone and thiopentone) and of their drug-free solutions on the production of oxygen radicals by neutrophils were tested by N-formylmethionyl-leucyl-phenylalanine (FMLP)-induced granulocyte chemiluminescence and in a cell-free chemiluminescence system. Methohexitone had no effect on neutrophil chemiluminescence. Pentobarbitone, phenobarbitone and thiopentone dose-dependently decreased FMLP-induced chemiluminescence and cell-free chemiluminescence. Suppression of neutrophil chemiluminescence by pentobarbitone and phenobarbitone was due to effects of the drug-free solutions and an osmolality greater than 360 mosmol kg-1. Only thiopentone suppressed granulocyte chemiluminescence drug-specifically. The physicochemical properties of commercially available barbiturate preparations and their solutions, as well as free radical scavenging capacity, have to be considered if these preparations are used to evaluate drug-specific effects on the production of oxygen radicals by neutrophils.

Benzodiazepines and their solvents influence neutrophil granulocyte function.

We have examined the effects of commercially available preparations and drug-free solvents of diazepam (Valium, Diazepam-Lipuro) and midazolam (Dormicum) by N-formylmethionyl-leucylphenylalanine (FMLP)- and zymosan-induced polymorphonuclear cell (PMN) chemiluminescence and in a cell-free chemiluminescence system. In the case of Valium, drug-free solvent and diazepam suppressed PMN chemiluminescence. With Diazepam-Lipuro, the solvent stimulated and diazepam inhibited PMN chemiluminescence. With midazolam (Dormicum), only the active drug depressed PMN chemiluminescence. FMLP-induced PMN chemiluminescence was depressed 10-100 fold more by diazepam and midazolam than zymosan-induced chemiluminescence.