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Blunt Chest Trauma in Mice after Cigarette Smoke-Exposure: Effects of Mechanical Ventilation with 100% O2.

Wagner K, Gröger M, McCook O, Scheuerle A, Asfar P, Stahl B, Huber-Lang M, Ignatius A, Jung B, Duechs M, Möller P, Georgieff M, Calzia E, Radermacher P, Wagner F - PLoS ONE (2015)

Bottom Line: This effect coincided with increased activated caspase-3, nitrotyrosine, P2XR4, and P2XR7 expression, NF-κB activation, and reduced HIF-1α expression.Hyperoxia did not further affect lung mechanics, gas exchange, pulmonary and systemic cytokine and chemokine concentrations, or histological scoring, except for some patchy alveolar edema in CS exposed mice.Overall, CS exposure aggravated post-traumatic inflammation, nitrosative stress and thereby organ dysfunction and injury; short-term, lung-protective, hyperoxic mechanical ventilation have no major beneficial effect despite attenuation of nitrosative stress, possibly due to compensation of by regional alveolar hypoxia and/or consecutive hypoxemia, resulting in down-regulation of HIF-1α expression.

View Article: PubMed Central - PubMed

Affiliation: Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Ulm, Germany; Klinik für Anästhesiologie, Universitätsklinikum, Ulm, Germany.

ABSTRACT
Cigarette smoking (CS) aggravates post-traumatic acute lung injury and increases ventilator-induced lung injury due to more severe tissue inflammation and apoptosis. Hyper-inflammation after chest trauma is due to the physical damage, the drop in alveolar PO2, and the consecutive hypoxemia and tissue hypoxia. Therefore, we tested the hypotheses that 1) CS exposure prior to blunt chest trauma causes more severe post-traumatic inflammation and thereby aggravates lung injury, and that 2) hyperoxia may attenuate this effect. Immediately after blast wave-induced blunt chest trauma, mice (n=32) with or without 3-4 weeks of CS exposure underwent 4 hours of pressure-controlled, thoraco-pulmonary compliance-titrated, lung-protective mechanical ventilation with air or 100% O2. Hemodynamics, lung mechanics, gas exchange, and acid-base status were measured together with blood and tissue cytokine and chemokine concentrations, heme oxygenase-1 (HO-1), activated caspase-3, and hypoxia-inducible factor 1-α (HIF-1α) expression, nuclear factor-κB (NF-κB) activation, nitrotyrosine formation, purinergic receptor 2X4 (P2XR4) and 2X7 (P2XR7) expression, and histological scoring. CS exposure prior to chest trauma lead to higher pulmonary compliance and lower PaO2 and Horovitz-index, associated with increased tissue IL-18 and blood MCP-1 concentrations, a 2-4-fold higher inflammatory cell infiltration, and more pronounced alveolar membrane thickening. This effect coincided with increased activated caspase-3, nitrotyrosine, P2XR4, and P2XR7 expression, NF-κB activation, and reduced HIF-1α expression. Hyperoxia did not further affect lung mechanics, gas exchange, pulmonary and systemic cytokine and chemokine concentrations, or histological scoring, except for some patchy alveolar edema in CS exposed mice. However, hyperoxia attenuated tissue HIF-1α, nitrotyrosine, P2XR7, and P2XR4 expression, while it increased HO-1 formation in CS exposed mice. Overall, CS exposure aggravated post-traumatic inflammation, nitrosative stress and thereby organ dysfunction and injury; short-term, lung-protective, hyperoxic mechanical ventilation have no major beneficial effect despite attenuation of nitrosative stress, possibly due to compensation of by regional alveolar hypoxia and/or consecutive hypoxemia, resulting in down-regulation of HIF-1α expression.

No MeSH data available.


Related in: MedlinePlus

Results of the immune blotting for activated caspase-3.Original western blots and quantitative analysis of lung tissue expression of activated caspase-3 from mice without (open boxplots; n = 8 each) and with (hatched boxplots; n = 7 each) cigarette smoke exposure prior to blunt chest trauma and mechanically ventilated with air (white boxplots) and 100% O2 (grey boxplots) together with two blots each (right part of blot panel) from control animals that did not undergo cigarette smoke exposure, anaesthesia, chest trauma, and surgery. All data are median (quartiles, range) as fold increase over values from control animals; § p < 0.05 vs. corresponding cigarette smoke exposure group, $ p < 0.05 vs. corresponding air ventilation group (Kruskall-Wallis analysis of variance on ranks with post-hoc Dunn’s test for multiple comparisons).
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pone.0132810.g003: Results of the immune blotting for activated caspase-3.Original western blots and quantitative analysis of lung tissue expression of activated caspase-3 from mice without (open boxplots; n = 8 each) and with (hatched boxplots; n = 7 each) cigarette smoke exposure prior to blunt chest trauma and mechanically ventilated with air (white boxplots) and 100% O2 (grey boxplots) together with two blots each (right part of blot panel) from control animals that did not undergo cigarette smoke exposure, anaesthesia, chest trauma, and surgery. All data are median (quartiles, range) as fold increase over values from control animals; § p < 0.05 vs. corresponding cigarette smoke exposure group, $ p < 0.05 vs. corresponding air ventilation group (Kruskall-Wallis analysis of variance on ranks with post-hoc Dunn’s test for multiple comparisons).

Mentions: Typical examples of the histological items are shown in Fig 1. Whereas CS exposure did not affect post-traumatic lung tissue HO-1 expression (Fig 2), it markedly increased activated caspase-3 (Fig 3) expression and NF-κB activation (Fig 4), and reduced HIF-1α formation (Fig 5). CS exposure was also associated with increased tissue nitrotyrosine formation (Fig 6), P2XR7 and P2XR4 expression (Figs 7 and 8).


Blunt Chest Trauma in Mice after Cigarette Smoke-Exposure: Effects of Mechanical Ventilation with 100% O2.

Wagner K, Gröger M, McCook O, Scheuerle A, Asfar P, Stahl B, Huber-Lang M, Ignatius A, Jung B, Duechs M, Möller P, Georgieff M, Calzia E, Radermacher P, Wagner F - PLoS ONE (2015)

Results of the immune blotting for activated caspase-3.Original western blots and quantitative analysis of lung tissue expression of activated caspase-3 from mice without (open boxplots; n = 8 each) and with (hatched boxplots; n = 7 each) cigarette smoke exposure prior to blunt chest trauma and mechanically ventilated with air (white boxplots) and 100% O2 (grey boxplots) together with two blots each (right part of blot panel) from control animals that did not undergo cigarette smoke exposure, anaesthesia, chest trauma, and surgery. All data are median (quartiles, range) as fold increase over values from control animals; § p < 0.05 vs. corresponding cigarette smoke exposure group, $ p < 0.05 vs. corresponding air ventilation group (Kruskall-Wallis analysis of variance on ranks with post-hoc Dunn’s test for multiple comparisons).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520521&req=5

pone.0132810.g003: Results of the immune blotting for activated caspase-3.Original western blots and quantitative analysis of lung tissue expression of activated caspase-3 from mice without (open boxplots; n = 8 each) and with (hatched boxplots; n = 7 each) cigarette smoke exposure prior to blunt chest trauma and mechanically ventilated with air (white boxplots) and 100% O2 (grey boxplots) together with two blots each (right part of blot panel) from control animals that did not undergo cigarette smoke exposure, anaesthesia, chest trauma, and surgery. All data are median (quartiles, range) as fold increase over values from control animals; § p < 0.05 vs. corresponding cigarette smoke exposure group, $ p < 0.05 vs. corresponding air ventilation group (Kruskall-Wallis analysis of variance on ranks with post-hoc Dunn’s test for multiple comparisons).
Mentions: Typical examples of the histological items are shown in Fig 1. Whereas CS exposure did not affect post-traumatic lung tissue HO-1 expression (Fig 2), it markedly increased activated caspase-3 (Fig 3) expression and NF-κB activation (Fig 4), and reduced HIF-1α formation (Fig 5). CS exposure was also associated with increased tissue nitrotyrosine formation (Fig 6), P2XR7 and P2XR4 expression (Figs 7 and 8).

Bottom Line: This effect coincided with increased activated caspase-3, nitrotyrosine, P2XR4, and P2XR7 expression, NF-κB activation, and reduced HIF-1α expression.Hyperoxia did not further affect lung mechanics, gas exchange, pulmonary and systemic cytokine and chemokine concentrations, or histological scoring, except for some patchy alveolar edema in CS exposed mice.Overall, CS exposure aggravated post-traumatic inflammation, nitrosative stress and thereby organ dysfunction and injury; short-term, lung-protective, hyperoxic mechanical ventilation have no major beneficial effect despite attenuation of nitrosative stress, possibly due to compensation of by regional alveolar hypoxia and/or consecutive hypoxemia, resulting in down-regulation of HIF-1α expression.

View Article: PubMed Central - PubMed

Affiliation: Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Ulm, Germany; Klinik für Anästhesiologie, Universitätsklinikum, Ulm, Germany.

ABSTRACT
Cigarette smoking (CS) aggravates post-traumatic acute lung injury and increases ventilator-induced lung injury due to more severe tissue inflammation and apoptosis. Hyper-inflammation after chest trauma is due to the physical damage, the drop in alveolar PO2, and the consecutive hypoxemia and tissue hypoxia. Therefore, we tested the hypotheses that 1) CS exposure prior to blunt chest trauma causes more severe post-traumatic inflammation and thereby aggravates lung injury, and that 2) hyperoxia may attenuate this effect. Immediately after blast wave-induced blunt chest trauma, mice (n=32) with or without 3-4 weeks of CS exposure underwent 4 hours of pressure-controlled, thoraco-pulmonary compliance-titrated, lung-protective mechanical ventilation with air or 100% O2. Hemodynamics, lung mechanics, gas exchange, and acid-base status were measured together with blood and tissue cytokine and chemokine concentrations, heme oxygenase-1 (HO-1), activated caspase-3, and hypoxia-inducible factor 1-α (HIF-1α) expression, nuclear factor-κB (NF-κB) activation, nitrotyrosine formation, purinergic receptor 2X4 (P2XR4) and 2X7 (P2XR7) expression, and histological scoring. CS exposure prior to chest trauma lead to higher pulmonary compliance and lower PaO2 and Horovitz-index, associated with increased tissue IL-18 and blood MCP-1 concentrations, a 2-4-fold higher inflammatory cell infiltration, and more pronounced alveolar membrane thickening. This effect coincided with increased activated caspase-3, nitrotyrosine, P2XR4, and P2XR7 expression, NF-κB activation, and reduced HIF-1α expression. Hyperoxia did not further affect lung mechanics, gas exchange, pulmonary and systemic cytokine and chemokine concentrations, or histological scoring, except for some patchy alveolar edema in CS exposed mice. However, hyperoxia attenuated tissue HIF-1α, nitrotyrosine, P2XR7, and P2XR4 expression, while it increased HO-1 formation in CS exposed mice. Overall, CS exposure aggravated post-traumatic inflammation, nitrosative stress and thereby organ dysfunction and injury; short-term, lung-protective, hyperoxic mechanical ventilation have no major beneficial effect despite attenuation of nitrosative stress, possibly due to compensation of by regional alveolar hypoxia and/or consecutive hypoxemia, resulting in down-regulation of HIF-1α expression.

No MeSH data available.


Related in: MedlinePlus