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- Title
Effects of anesthetic regimes on inflammatory responses in a rat model of acute lung injury.
- Authors
Fortis, Spyridon; Spieth, Peter; Lu, Wei-Yang; Parotto, Matteo; Haitsma, Jack; Slutsky, Arthur; Zhong, Nanshan; Mazer, C.; Zhang, Haibo
- Abstract
Purpose: Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter through activation of GABA receptors. Volatile anesthetics activate type-A (GABA) receptors resulting in inhibition of synaptic transmission. Lung epithelial cells have been recently found to express GABA receptors that exert anti-inflammatory properties. We hypothesized that the volatile anesthetic sevoflurane (SEVO) attenuates lung inflammation through activation of lung epithelial GABA 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 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 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 signaling pathways.
- Subjects
GABA receptors; LUNG injuries; LABORATORY rats; NEURAL transmission; KETAMINE; CYTOKINE receptors
- Publication
Intensive Care Medicine, 2012, Vol 38, Issue 9, p1548
- ISSN
0342-4642
- Publication type
Article
- DOI
10.1007/s00134-012-2610-4