Abstract
BackgroundMechanical ventilation and hyperoxia have the potential to independently promote lung injury and inflammation. Our purpose was to study both time- and dose-dependent effects of supplemental oxygen in an experimental model of mechanically ventilated mice.MethodsHealthy male C57Bl/6J mice, aged 9–10 weeks, were intraperitoneally anesthetized and randomly assigned to the mechanically ventilated group or the control group. In total, 100 mice were tracheotomized and mechanically ventilated for either 8 or 12 h after allocation to different settings for the applied fractions of inspired oxygen (FiO2, 30, 50, or 90%) and tidal volumes (7.5 or 15 ml/kg). After euthanisation arterial blood, bronchoalveolar lavage fluid (BALf) and tissues were collected for analyses.ResultsMechanical ventilation significantly increased the lung injury score (P < 0.05), mean protein content (P < 0.001), and the mean number of cells (P < 0.01), including neutrophils in BALf (P < 0.001). In mice ventilated for 12 h, a significant increase in TNF-α, IFN-γ, IL-1β, IL-10, and MCP-1 (P < 0.01) was observed with 90% FiO2, whereas IL-6 showed a decreasing trend (P for trend = 0.03) across FiO2 groups. KC, MIP-2, and sRAGE were similar between FiO2 groups. HMGB-1 was significantly higher in BALf of mechanically ventilated mice compared to controls and showed a gradual increase in expression with increasing FiO2. Cytokine and chemokine levels in BALf did not markedly differ between FiO2 groups after 8 h of ventilation. Differences between the tidal volume groups were small and did not appear to significantly interact with the oxygen levels.ConclusionsWe demonstrated a severe vascular leakage and a pro-inflammatory pulmonary response in mechanically ventilated mice, which was enhanced by severe hyperoxia and longer duration of mechanical ventilation. Prolonged ventilation with high oxygen concentrations induced a time-dependent immune response characterized by elevated levels of neutrophils, cytokines, and chemokines in the pulmonary compartment.
Highlights
Mechanical ventilation and hyperoxia have the potential to independently promote lung injury and inflammation
Hypothesizing that hyperoxia induces a dose-dependent gradual inflammatory response that may be aggravated by prolonged periods of mechanical ventilation, our purpose was to induce hyperoxia in mice and study both time- and dose-dependent inflammation effects of supplemental oxygen during prolonged ventilatory support with protective and injurious tidal volumes
In mice ventilated for 12 h, a significantly increasing trend in Tumor necrosis factor-α (TNF-α), IFN-γ, IL-1β, IL-10, and Monocyte Chemoattractant Protein-1 (MCP-1) (Fig. 3, P for trend
Summary
Mechanical ventilation and hyperoxia have the potential to independently promote lung injury and inflammation. Inspiratory fractions of oxygen (FiO2) typically exceed concentrations of atmospheric air and are frequently applied for prolonged periods during mechanical ventilation in patients suffering from severe respiratory distress. Both mechanical ventilation and hyperoxia can promote lung injury and induce adverse effects through diverse mechanisms. Hypothesizing that hyperoxia induces a dose-dependent gradual inflammatory response that may be aggravated by prolonged periods of mechanical ventilation, our purpose was to induce hyperoxia in mice and study both time- and dose-dependent inflammation effects of supplemental oxygen during prolonged ventilatory support with protective and injurious tidal volumes
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