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

Abstract

BackgroundVentilator-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.MethodsTwenty 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.ResultsHistopathology 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.ConclusionsSevoflurane 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.

Differential effects of sevoflurane on the metastatic potential and chemosensitivity of non-small-cell lung adenocarcinoma and renal cell carcinoma in vitro

“…Sevoflurane could be changing the balance of signal transduction to favour the Smad pathway. This is supported by a recent studies showing inhibition of the non-Smad pathway components p38 MAPK, 21 Akt, 23 and ERK 24 by sevoflurane in lung. Gordian and colleagues 25 found exogenous TGF-b1 enhances the chemosensitivity of A549.…”

The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury

“…The PI3K/Akt and p38 MAPK pathway exists extensively in cells and is involved in the regulation of a series of physiological activities such as cell apoptosis. Both propofol and sevoflurane were reported to regulate AKT and p38 expression levels [47][48][49]; however, this phenomenon was not observed in our study. As expected, propofol increased the phosphorylation of AKT but decreased the phosphorylation of Bad, while no changes were detected in the expression or phosphorylation of p38.…”

Alveolar formation is dysregulated by restricted nutrition but not excess sedation in preterm lambs managed by noninvasive support

“…Sedation of preterm infants receiving invasive mechanical ventilation may affect alveolar formation directly, by altering lung cell-signaling, or indirectly by prolonging mechanical ventilation, or disrupting nutritional intake and/or absorption (18, 19, 22, 23, 33). In our study, preterm lambs in the NIS+ES group tolerated sheep colostrum and milk.…”

“…Postnatal sedation may reduce postnatal nutrition and growth via effects on gastrointestinal motility, absorption, and blood flow (18–21). In the developing lung, sedation may also directly affect alveolar formation by disruption of lung cell-signaling pathways (22–24). …”