Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model.

TLDR

The study investigated how different ventilation strategies influence lung inflammatory mediators in the presence or absence of a preexisting inflammatory stimulus. In 55 Sprague‑Dawley rats, lungs were excised after 50 min of spontaneous breathing and ventilated for 2 h under one of four protocols (control, moderate volume/high PEEP, moderate volume/zero PEEP, high volume/zero PEEP) while cytokine levels were quantified by ELISA. Zero‑PEEP ventilation, particularly with high tidal volume, markedly reduced lung compliance and synergistically amplified cytokine release (e.g., 56‑fold TNFα increase) and c‑fos mRNA induction, whereas moderate‑volume/high‑PEEP ventilation produced only modest inflammatory changes, highlighting ventilation’s role in modulating lung inflammation.

Abstract

We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus. 55 Sprague-Dawley rats were randomized to either intravenous saline or lipopolysaccharide (LPS). After 50 min of spontaneous respiration, the lungs were excised and randomized to 2 h of ventilation with one of four strategies: (a) control (C), tidal volume (Vt) = 7 cc/kg, positive end expiratory pressure (PEEP) = 3 cm H2O; (b) moderate volume, high PEEP (MVHP), Vt = 15 cc/kg; PEEP = 10 cm H2O; (c) moderate volume, zero PEEP (MVZP), Vt = 15 cc/kg, PEEP = 0; or (d) high volume, zero PEEP (HVZP), Vt = 40 cc/kg, PEEP = 0. Ventilation with zero PEEP (MVZP, HVZP) resulted in significant reductions in lung compliance. Lung lavage levels of TNFalpha, IL-1beta, IL-6, IL-10, MIP-2, and IFNgamma were measured by ELISA. Zero PEEP in combination with high volume ventilation (HVZP) had a synergistic effect on cytokine levels (e.g., 56-fold increase of TNFalpha versus controls). Identical end inspiratory lung distention with PEEP (MVHP) resulted in only a three-fold increase in TNFalpha, whereas MVZP produced a six-fold increase in lavage TNFalpha. Northern blot analysis revealed a similar pattern (C, MVHP < MVZP < HVZP) for induction of c-fos mRNA. These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung, and thus may play a role in initiating or propagating a local, and possibly systemic inflammatory response.