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

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 cmH(2)O, I : E ratio of 1 : 4, and positive end expiratory pressure of 5 cmH(2)O. All animals were randomly assigned to one of three groups that were ventilated for 5 h with 10 cmH(2)O of PIP (Sham group, n = 7); 30 cmH(2)O of PIP (Control group, n = 7); or 30 cmH(2)O 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.