Interactions of lung stretch, hyperoxia, and MIP-2 production in ventilator-induced lung injury

TLDR

Positive‑pressure mechanical ventilation can cause ventilator‑induced lung injury (VILI). The study tested whether hyperoxia combined with large tidal volumes would worsen edema and neutrophil infiltration in VILI via stretch‑induced MIP‑2 production. In rats ventilated at 20 ml/kg, hyperoxia amplified pulmonary edema and neutrophil migration into the alveoli, and blocking MIP‑2 reduced migration by 51–65 %, indicating that stretch‑induced MIP‑2 drives neutrophil influx while hyperoxia may involve additional pathways.

Abstract

The use of positive pressure mechanical ventilation can cause ventilator-induced lung injury (VILI). We hypothesized that hyperoxia in combination with large tidal volumes (Vt) would accentuate noncardiogenic edema and neutrophil infiltration in VILI and be dependent on stretch-induced macrophage inflammatory protein-2 (MIP-2) production. In rats ventilated with Vt 20 ml/kg, there was pulmonary edema formation that was significantly increased by hyperoxia. Total lung neutrophil infiltration and MIP-2 in bronchoalveolar lavage (BAL) fluid were significantly elevated, in animals exposed to high Vt both on room air (RA) and with hyperoxia. Hyperoxia markedly augmented the migration of neutrophils into the alveoli. Anti-MIP-2 antibody blocked migration of neutrophils into the alveoli in RA by 51% and with hyperoxia by 65%. We concluded that neutrophil migration into the alveoli was dependent on stretch-induced MIP-2 production. Hyperoxia significantly increased edema formation and neutrophil migration into the alveoli with Vt 20 ml/kg, although BAL MIP-2 levels were nearly identical to Vt 20 ml/kg with RA, suggesting that other mechanisms may be involved in hyperoxia-augmented neutrophil alveolar content in VILI.