Korean J Anesthesiol.  2015 Feb;68(1):62-69. 10.4097/kjae.2015.68.1.62.

The volatile anesthetic sevoflurane attenuates ventilator-induced lung injury through inhibition of ERK1/2 and Akt signal transduction

• Kim SH
• Li M
• Pyeon TH
• So KY
• Kwak SH

• KMID: 2236191
• DOI: http://doi.org/10.4097/kjae.2015.68.1.62

Abstract

BACKGROUND
Ventilator-induced lung injury (VILI) sustained during mechanical ventilator support is still a cause of a high rate of morbidity and mortality in intensive care units and in operating rooms. VILI is characterized by pulmonary inflammation that appears to be mediated by proinflammatory cytokines. This study investigates whether the volatile anesthetic sevoflurane has an anti-inflammatory effect that attenuates VILI.
METHODS
Twenty one male rabbits were anesthetized and were mechanically ventilated with 50% oxygen at a peak inspiratory pressure (PIP) of 10 cmH2O, I : E ratio of 1 : 4, and positive end expiratory pressure of 5 cmH2O. All animals were randomly assigned to one of three groups that were ventilated for 5 h with 10 cmH2O of PIP (Sham group, n = 7); 30 cmH2O of PIP (Control group, n = 7); or 30 cmH2O of PIP and 0.8 vol% sevoflurane (Sevoflurane group, n = 7). The wet/dry weight (W/D) ratio and histopathology of the lung; concentration of interleukin-8 (IL-8) in the bronchoalveolar lavage fluid; and activation of extracellular signal-regulated kinases (ERK) 1/2, p38 mitogen-activated protein kinase, and Akt were measured in the lung tissue after completing the protocol.
RESULTS
Histopathology indicated that the sevoflurane group showed fewer inflammatory cells and architectural changes than the control group did. The W/D ratio [(5.36 +/- 0.13) versus (6.61 +/- 0.20)], expression of IL-8 [(144.08 +/- 14.61) versus (228.56 +/- 15.13) pg/ml] and phosphorylation of ERK1/2 and Akt decreased significantly in the sevoflurane group relative to the control group.
CONCLUSIONS
Sevoflurane attenuates VILI in rabbits mainly by inhibiting expression of IL-8, and Sevoflurane-induced inhibition of phosphorylated ERK1/2 and Akt might be a possible pathway for protection.

Keyword

Akt; ERK1/2; Sevoflurane; Ventilator-induced lung injury

MeSH Terms

Animals
Bronchoalveolar Lavage Fluid
Cytokines
Extracellular Signal-Regulated MAP Kinases
Humans
Intensive Care Units
Interleukin-8
Lung
Male
Mortality
Operating Rooms
Oxygen
Phosphorylation
Pneumonia
Positive-Pressure Respiration
Protein Kinases
Rabbits
Signal Transduction*
Ventilator-Induced Lung Injury*
Ventilators, Mechanical
Cytokines
Extracellular Signal-Regulated MAP Kinases
Interleukin-8
Oxygen
Protein Kinases