Abstract

PURPOSE
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.
CONCLUSION
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.

Links

Publisher Full Text

Authors

Fortis S, Spieth PM, Lu WY, Parotto M, Haitsma JJ, Slutsky AS, Zhong N, Mazer CD, Zhang H

Institution

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.

Source

Intensive care medicine 38:9 2012 Sep pg 1548-55

MeSH

Acute Lung Injury
Analysis of Variance
Anesthesia
Anesthetics, Dissociative
Anesthetics, General
Anesthetics, Inhalation
Animals
Bronchoalveolar Lavage
Disease Models, Animal
Hemodynamics
Humans
Inflammation
Ketamine
Lung
Methyl Ethers
Rats
Rats, Sprague-Dawley
Respiration, Artificial
Risk
Xylazine
gamma-Aminobutyric Acid

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22711173