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

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.

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.

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.

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.