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Intensive Care Med. 2012 Sep;38(9):1548-55. doi: 10.1007/s00134-012-2610-4. Epub 2012 Jun 19.

Effects of anesthetic regimes on inflammatory responses in a rat model of acute lung injury.

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  • 1Keenan 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.

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.

PMID:
22711173
[PubMed - indexed for MEDLINE]
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