Journal article
Effects of anesthetic regimes on inflammatory responses in a rat model of acute lung injury
Intensive care medicine, Vol.38(9), pp.1548-1555
09/2012
DOI: 10.1007/s00134-012-2610-4
PMCID: PMC4896809
PMID: 22711173
Abstract
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.
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.
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.
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.
Details
- Title: Subtitle
- Effects of anesthetic regimes on inflammatory responses in a rat model of acute lung injury
- Creators
- Spyridon Fortis - 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, CanadaPeter M SpiethWei-Yang LuMatteo ParottoJack J HaitsmaArthur S SlutskyNanshan ZhongC David MazerHaibo Zhang - University of Toronto
- Resource Type
- Journal article
- Publication Details
- Intensive care medicine, Vol.38(9), pp.1548-1555
- DOI
- 10.1007/s00134-012-2610-4
- PMID
- 22711173
- PMCID
- PMC4896809
- ISSN
- 0342-4642
- eISSN
- 1432-1238
- Grant note
- 69042-1 / Canadian Institutes of Health Research
- Language
- English
- Date published
- 09/2012
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094326702771
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