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[Intravenous anesthetics and human neutrophil granulocyte motility in vitro]
1Institut für Anaesthesiologie, Universität Würzburg.
Abstract:
Polymorphonuclear leukocytes (PMN) form a major part of the body's nonspecific first line of defense. An early event, prerequisite for the effective restriction of microbial invasions, is the chemotactic movement of activated neutrophils towards the invading organisms. To date, only limited and contradictory data exist regarding the effects of various intravenous anesthetic agents on neutrophil migration. In this study, the influence of ketamine, etomidate, midazolam, diazepam, and six commonly used i.v. barbiturates (hexo-, pheno-, pentobarbital, methohexital, thiopental, thiobutobarbital) on the in vitro motility of isolated human PMN was tested. Purified PMN (greater than 95%) were obtained from venous blood samples of healthy adults by dextran sedimentation, subsequent ammonium chloride treatment for red blood cell lysis, and Ficoll-Hypaque gradient centrifugation. Random and chemotactic migration were assessed under 1% agarose in the presence of 10(-3)-10(-7) M logarithmic dilutions of the agents in antibiotic free migration medium (MEM). N-fMet-Leu-Phe (FMLP) served as the standardized chemical attractant (10(-7) M). PMN motility was unaffected by ketamine and etomidate, but a significant (P less than 0.001), dose - related depression could be observed with both benzodiazepines at concentrations exceeding 10(-5) M (Fig. 1). Except at 10(-3) M concentration, this migratory inhibition proved to be easily reversible (Fig. 3). At the highest concentration tested (10(-3) M), all the barbiturates caused a significant (P less than 0.001) but completely reversible depression of random as well as chemotactic PMN migration (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Intravenous anesthetic agents like benzodiazepines and barbiturates can impair neutrophil migration, a key immune defense. Ketamine and etomidate did not affect this crucial cell movement.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMN) are critical for the innate immune system's first line of defense.
- Neutrophil chemotaxis is essential for restricting microbial invasions.
- Existing data on intravenous anesthetics' effects on neutrophil migration are limited and contradictory.
Purpose of the Study:
- To investigate the in vitro effects of ketamine, etomidate, midazolam, diazepam, and various barbiturates on human neutrophil migration.
- To determine dose-dependent effects and reversibility of anesthetic-induced changes in PMN motility.
Main Methods:
- Isolated human PMN were prepared using dextran sedimentation, ammonium chloride lysis, and Ficoll-Hypaque gradient centrifugation.
- Random and chemotactic migration assays were performed in agarose using logarithmic dilutions of anesthetics.
- N-formyl-methionyl-leucyl-phenylalanine (FMLP) was used as a chemoattractant.
Main Results:
- Ketamine and etomidate did not significantly alter PMN motility.
- Benzodiazepines (midazolam, diazepam) caused a dose-dependent, reversible depression of PMN migration at concentrations above 10(-5) M.
- All tested barbiturates significantly inhibited both random and chemotactic PMN migration at 10(-3) M, with effects being fully reversible.
Conclusions:
- Certain intravenous anesthetics, specifically benzodiazepines and barbiturates, can impair neutrophil migration in a dose-dependent manner.
- The inhibitory effects of these anesthetics on PMN motility are largely reversible.
- Ketamine and etomidate do not appear to affect neutrophil migration.