Low tidal volume ventilation preconditioning ameliorates lipopolysaccharide-induced acute lung injury in rats

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Abstract

Background:

Effects of low tidal volume (LTV) ventilation preconditioning in endotoxin-induced acute lung injury (ALI) have not been studied. We investigated the effect of LTV ventilation pre-treatment on ALI induced by lipopolysaccharide (LPS) in rats.

Methods:

Male Sprague–Dawley rats were assigned to four groups (n = 8 each): (1) sham rats injected (i.p.) with 0.9% (physiologic) saline; sham rats pre-treated with tidal volume 6 ml/kg ventilation for 1 h followed by injection (i.p.) of physiologic saline (mechanical ventilation; MV-saline group); (2) LPS group (rats injected with LPS (i.p.); rats pre-treated with tidal volume 6 ml/kg ventilation for 1 h before injection (i.p.) with LPS (MV-LPS group). Animals were observed for 6 h. ALI extent was evaluated by lung wet-to-dry ratio, Evans Blue Dye extravasation, and histologic examination. We measured levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Apoptotic index (AI) and the expression of pulmonary RhoA, ROCK2 mRNA, and ROCK1 protein in lung alveolar cells was determined.

Results:

Lipopolysaccharide caused severe ALI, as evidenced by increases in ALI extent, impairment of pulmonary functions, and increases in pulmonary levels of TNF-α, IL-1β, IL-6, and AI. LTV ventilation preconditioning mitigated LPS-induced increases in release of pulmonary pro-inflammatory cytokines and AI of alveolar cells. Expression of pulmonary RhoA, ROCK2 mRNA, and ROCK1 protein was upregulated by LPS and reduced by LTV ventilation pre-treatment.

Conclusion:

Low tidal volume ventilation preconditioning can attenuate release of pulmonary pro-inflammatory cytokines and decrease the AI induced by severe sepsis. Early protection seems to be mediated partly through inhibition of activation of a Rho pathway.

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