Inhibitory effects of S-(-) and R-(+) bupivacaine on neutrophil function.
BACKGROUND
Local anesthetics inhibit migration, enzyme release and superoxide anion generation of polymorphonuclear leukocytes (PMN). Due to their ability to phagocytose and kill bacteria PMN represent a major defense mechanism in the circulating blood. In this study we determined the influence of racemic bupivacaine and its enantiomers on neutrophil phagocytic activity, oxidative burst as well as surface expression of complement and Fcgamma receptors.


METHODS
Venous blood was pre-incubated with different concentrations of either racemic bupivacaine, R-(+) or S-(-) bupivacaine. Fluoresceine isothiocyanate (FITC)-labeled antibodies against Fcgamma receptor III (CD16), complement receptor 1 (CD35) and complement receptor 3 (CD11b) were used to determine surface receptor expression. Phagocytic activity was measured by ingestion of FITC-labeled vital Staphylococcus aureus. Oxidative burst was determined by conversion of nonfluorescent dihydrorhodamine 123 into fluorescent rhodamine 123. Fluorescent intensity of each sample was determined by flow cytometry.


RESULTS
Racemic bupivacaine inhibited surface receptor expression, phagocytosis, and oxidative burst in a time- and concentration-dependent manner. Although the S-(-) enantiomer exerted significantly less inhibitory action on neutrophil function compared to R-(+) and racemic bupivacaine, these effects were small compared to the overall changes.


CONCLUSIONS
These findings suggest that bupivacaine impairs surface receptor expression and may thereby contribute to reduced phagocytic activity and oxidative burst. Enantiomer-specific effects of bupivacaine may play a minor role in the inhibition of these leukocyte functions.
Welters
I D
ID
Department of Anaesthesiology and Intensive Care Medicine, Justus-Liebig-Universität, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany. Ingeborg.D.Welters@chiru.med.uni-giessen.de
Menzebach
A
A
Langefeld
T W
TW
Menzebach
M
M
Hempelmann
G
G
D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology*; D002045:Bupivacaine / Q000494:pharmacology*; D003172:Complement C1 / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011951:Receptors, Complement / Q000187:drug effects; D011961:Receptors, Fc / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects; D013237:Stereoisomerism
D000779:Anesthetics, Local; D003172:Complement C1; D003176:Complement C3; D008565:Membrane Proteins; D011951:Receptors, Complement; D011961:Receptors, Fc; D002045:Bupivacaine