Hyperoxia increases ventilator-induced lung injury via mitogen-activated protein kinases: a prospective, controlled animal experiment

Abstract

Introduction Large-tidal volume (V T ) mechanical ventilation and hyperoxia used in patients with acute respiratory distress syndrome can damage pulmonary epithelial cells through lung inflammation and apoptotic cell death. Hyperoxia has been shown to increase ventilator-induced lung injury, but the mechanisms regulating interaction between large V T and hyperoxia are unclear. We hypothesized that the addition of hyperoxia to large-V T ventilation would increase neutrophil infiltration by upregulation of the cytokine macrophage inflammatory protein-2 (MIP-2) and would increase apoptosis via the mitogen-activated protein kinase pathways.

Should Oxygen Therapy Be Tightly Regulated to Minimize Hyperoxia in Critically Ill Patients?

“…2), 28 and lung compliance, 28,32,33 increased inflammatory mediator expression ( Fig. 3) 24,[26][27][28]31,36 as well as increased apoptosis, 26,33,34 and increased alveolar infiltration by neutrophils. 24,26,27,[31][32][33]36 Similar results were found even when moderate hyperoxia (F IO 2 ϭ 0.5) was combined with a V T of 25 mL/kg.…”

“…24,[26][27][28][29][30][31][32][33][34][35][36] These models mimic common clinical strategies in managing ARDS and other forms of acute respiratory failure before the advent of lung-protective ventilation. In brief, compared with controls, high-V T ventilation with ambient F IO 2 (0.21), or a physiologic V T with hyperoxia, the combination of high-V T (18 -30 mL/kg) ventilation, and hyperoxia (F IO 2 ϭ 0.8 -1.0) markedly enhanced numerous signifiers for VILI, including: altered-permeability pulmonary edema formation, 24,26,27,31,32 diffuse interstitial and alveolar hemorrhage, 33,34 decreased surfactant production (Fig. 2), 28 and lung compliance, 28,32,33 increased inflammatory mediator expression ( Fig.…”

“…3) 24,[26][27][28]31,36 as well as increased apoptosis, 26,33,34 and increased alveolar infiltration by neutrophils. 24,26,27,[31][32][33]36 Similar results were found even when moderate hyperoxia (F IO 2 ϭ 0.5) was combined with a V T of 25 mL/kg. 29 Although several of the studies cited above examined the effects using either a neonatal 31,32 or an adult animal model, 24,[26][27][28][29] the pathological findings have been similar.…”

Ventilator-Induced Lug Injury and Acute Respiratory Distress Syndrome: A Basic Science Review

“…Hyperoxia has been shown to increase VILI, but the mechanisms regulating interaction between large tidal volume (VT) and hyperoxia are still unclear. Li et al [32] hypothesized that the addition of hyperoxia to large tidal volume ventilation would increase neutrophil infiltration by upregulation of the cytokine macrophage inflammatory protein-2 (MIP-2) and would increase apoptosis via the mitogen-activated protein kinase pathways. Authors concluded that hyperoxia increased high-VT-induced apoptotic and non-apoptotic epithelial cell injury and resulted in increased lung neutrophil influx.…”

Ventilator-Induced Lung Injury: Mechanisms and Future Therapeutic Interventions

“…Previously, in vitro studies demonstrated that mechanical stretch may activate apoptotic cell death (dos Santos et al, 2004;Edwards et al, 1999;Hammerschmidt et al, 2004). Moreover, several investigators reported enhanced apoptosis after 2 to 5 hours of mechanical ventilation with high tidal volumes (Chiang et al, 2011;Le et al, 2008;Li et al, 2007). Although the precise role of necrotic cell death has not been elucidated in VILI yet, it has been demonstrated in vitro that mechanical stretch as such induces necrosis (Hammerschmidt et al, 2004;Tschumperlin et al, 2000).…”