Effect of inhaled and intravenous lidocaine on inflammatory reaction in endotoxaemic rats.
OBJECTIVE
Systemically administered lidocaine has been shown to have anti-inflammatory properties. Inhalation is an attractive way of application because of high pulmonary compound concentrations and potentially fewer systemic side effects. The aim of this study was to clarify whether inhaled or, likewise, intravenous lidocaine can attenuate the inflammatory response in a model of experimental endotoxaemia in the rat.


METHODS
Animals randomly received (nine animals in each group) lidocaine, either aerosolized 4 mg kg(-1) (Lid(Ae4.0)) and 0.4 mg kg(-1) (Lid(Ae0.4)) or 4 mg kg(-1) intravenously (Lid(iv)) before intravenous injection of 5 mg kg(-1) lipopolysaccharide (LPS). Administration of lidocaine was repeated after 2 h. Additional control animals were observed either without (sham) or with the infusion of LPS. Following 5 h of experimental endotoxaemia, the concentrations of tumour necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta) and IL-6 were measured in bronchoalveolar lavage fluid and blood plasma. Release of nitrite in ex-vivo cultured alveolar macrophages was measured by Griess assay.


RESULTS
Bronchoalveolar lavage fluid levels of IL-1beta and TNFalpha in Lid(Ae4.0) (IL-1beta, -47%; TNFalpha, -41%; P < 0.05) and Lid(iv) (IL-1beta, -55%; TNFalpha, -54%; P < 0.05) but not in Lid(Ae0.4) were significantly lower than in LPS. Plasma cytokine levels were not attenuated. Nitrite was found to be significantly reduced in Lid(Ae4.0) (-46%), Lid(Ae0.4) (-39%) and Lid(iv) (-41%) when compared with LPS (P < 0.05, respectively).


CONCLUSIONS
Pretreatment of endotoxaemic rats either with Lid(Ae4.0) or with Lid(iv) attenuated the levels of proinflammatory mediators in bronchoalveolar lavage fluid. Plasma cytokine levels were not affected. Nebulized lidocaine (0.4 mg kg(-1)) inhibited the nitrite release but did not affect the cytokine levels.
Flondor
Michael
M
Department of Anaesthesiology, Ludwig Maximilian University of Munich, Munich, Germany. mvflondor@gmail.com
Listle
Holger
H
Kemming
Gregor I
GI
Zwissler
Bernhard
B
Hofstetter
Christian
C
D000336:Aerosols; D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D019446:Endotoxemia / Q000188:drug therapy*; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008012:Lidocaine / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000336:Aerosols; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D008012:Lidocaine