Effects of anesthetic regimes on inflammatory responses in a rat model of acute lung injury.
OBJECTIVE
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter through activation of GABA receptors. Volatile anesthetics activate type-A (GABA(A)) receptors resulting in inhibition of synaptic transmission. Lung epithelial cells have been recently found to express GABA(A) receptors that exert anti-inflammatory properties. We hypothesized that the volatile anesthetic sevoflurane (SEVO) attenuates lung inflammation through activation of lung epithelial GABA(A) receptors.


METHODS
Sprague-Dawley rats were anesthetized with SEVO or ketamine/xylazine (KX). Acute lung inflammation was induced by intratracheal instillation of endotoxin, followed by mechanical ventilation for 4 h at a tidal volume of 15 mL/kg without positive end-expiratory pressure (two-hit lung injury model). To examine the specific effects of GABA, healthy human lung epithelial cells (BEAS-2B) were challenged with endotoxin in the presence and absence of GABA with and without addition of the GABA(A) receptor antagonist picrotoxin.


RESULTS
Anesthesia with SEVO improved oxygenation and reduced pulmonary cytokine responses compared to KX. This phenomenon was associated with increased expression of the π subunit of GABA(A) receptors and glutamic acid decarboxylase (GAD). The endotoxin-induced cytokine release from BEAS-2B cells was attenuated by the treatment with GABA, which was reversed by the administration of picrotoxin.


CONCLUSIONS
Anesthesia with SEVO suppresses pulmonary inflammation and thus protects the lung from the two-hit injury. The anti-inflammatory effect of SEVO is likely due to activation of pulmonary GABA(A) signaling pathways.
Keenan Research Center, Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Room 619 LKSKI, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
Spyridon
S
Fortis
Peter M
PM
Spieth
Wei-Yang
WY
Lu
Matteo
M
Parotto
Jack J
JJ
Haitsma
Arthur S
AS
Slutsky
Nanshan
N
Zhong
C David
CD
Mazer
Haibo
H
Zhang
D055371:Acute Lung Injury / Q000209:etiology* / Q000473:pathology; D000704:Analysis of Variance; D000758:Anesthesia / Q000009:adverse effects*; D000778:Anesthetics, Dissociative / Q000009:adverse effects; D018681:Anesthetics, General / Q000009:adverse effects*; D018685:Anesthetics, Inhalation / Q000009:adverse effects; D000818:Animals; D018893:Bronchoalveolar Lavage; D004195:Disease Models, Animal; D006439:Hemodynamics; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D007649:Ketamine / Q000009:adverse effects; D008168:Lung / Q000166:cytology / Q000473:pathology*; D008738:Methyl Ethers / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D012306:Risk; D000077149:Sevoflurane; D014991:Xylazine / Q000009:adverse effects; D005680:gamma-Aminobutyric Acid
D000778:Anesthetics, Dissociative; D018681:Anesthetics, General; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D014991:Xylazine; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid; D007649:Ketamine