TY - JOUR
T1 - Hyperoxia provokes a time- and dose-dependent inflammatory response in mechanically ventilated mice, irrespective of tidal volumes
AU - Helmerhorst, Hendrik J.F.
AU - Schouten, Laura R.A.
AU - Wagenaar, Gerry T.M.
AU - Juffermans, Nicole P.
AU - Roelofs, Joris J.T.H.
AU - Schultz, Marcus J.
AU - de Jonge, Evert
AU - van Westerloo, David J.
N1 - Publisher Copyright: © 2017, The Author(s).
PY - 2017
Y1 - 2017
N2 - Mechanical 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. Healthy 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. Mechanical 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. We 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
AB - Mechanical 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. Healthy 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. Mechanical 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. We 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
KW - Hyperoxia
KW - Inflammation
KW - Mechanical ventilation
KW - Oxygen toxicity
KW - VILI
KW - mice
UR - http://www.scopus.com/inward/record.url?scp=85028061390&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s40635-017-0142-5
DO - https://doi.org/10.1186/s40635-017-0142-5
M3 - Article
C2 - 28550659
SN - 2197-425X
VL - 5
JO - Intensive Care Medicine Experimental
JF - Intensive Care Medicine Experimental
IS - 1
M1 - 27
ER -