Influence of lidocaine on endotoxin-induced leukocyte-endothelial cell adhesion and macromolecular leakage in vivo.
BACKGROUND
Endotoxin activates leukocyte-endothelial cell adhesion, vascular leakage, and changes in vascular micro-hemodynamics. The aim of this study was to determine whether lidocaine, which inhibits the activation of leukocytes, could attenuate microcirculatory disturbances during endotoxemia.


METHODS
Thirty anesthetized male rats were randomly assigned to receive one of three treatments (n = 10 for each group): infusion of saline (control group), infusion of Escherichia coli endotoxin (LPS group: 2 mg x kg(-1) x h(-1) lipopolysaccharides) without lidocaine treatment, or infusion of endotoxin with lidocaine pretreatment 30 min before baseline measurements (lidocaine group: intravenous bolus of 2 mg/kg and continuous infusion of 2 mg x kg(-1) x h(-1)). Leukocyte adherence, erythrocyte velocity (V(RBC), and vessel diameters (Dv) were determined at baseline and at 60 and 120 min in mesenteric postcapillary venules using in vivo videomicroscopy. Macromolecular leakage was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wall shear rate (tau) was calculated according to the equation tau = 8 x V(RBC) x Dv(-1).


RESULTS
Lidocaine significantly attenuated the increase of leukocyte adherence during endotoxemia. There were no significant differences of tau within or between the groups. Macromolecular leakage exhibited the greatest increase in the LPS group. In the lidocaine group, it was significantly decreased but still increased compared with the control group.


CONCLUSIONS
These results show that lidocaine attenuates endotoxin-induced alterations in leukocyte-endothelial cell adhesion and macromolecular leakage, which suggests that lidocaine may have a therapeutic role in preventing endothelial damage in sepsis.
Schmidt
W
W
Department of Anesthesiology, University of Heidelberg, Germany. werner.schmidt@urz.uni-heidelberg.de
Schmidt
H
H
Bauer
H
H
Gebhard
M M
MM
Martin
E
E
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019446:Endotoxemia / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008012:Lidocaine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy
D000779:Anesthetics, Local; D008012:Lidocaine