Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat.
<h4>Background</h4>Short-term mechanical ventilation (MV) protects against sepsis-induced diaphragmatic dysfunction. Prolonged MV induces diaphragmatic dysfunction in non-septic animals, but few reports describe the effects of prolonged MV in sepsis. We hypothesized that prolonged MV is...
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0200429&type=printable |
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| author | Matthieu Le Dinh Serge Carreira Julie Obert Ghislaine Gayan-Ramirez Bruno Riou Maud Beuvin Thomas Similowski Catherine Coirault Alexandre Demoule |
| author_facet | Matthieu Le Dinh Serge Carreira Julie Obert Ghislaine Gayan-Ramirez Bruno Riou Maud Beuvin Thomas Similowski Catherine Coirault Alexandre Demoule |
| author_sort | Matthieu Le Dinh |
| collection | DOAJ |
| description | <h4>Background</h4>Short-term mechanical ventilation (MV) protects against sepsis-induced diaphragmatic dysfunction. Prolonged MV induces diaphragmatic dysfunction in non-septic animals, but few reports describe the effects of prolonged MV in sepsis. We hypothesized that prolonged MV is not protective but worsens the diaphragmatic dysfunction induced by a mild sepsis, because MV and sepsis share key signaling mechanisms, such as cytokine upregulation.<h4>Method</h4>We studied the impact of prolonged MV (12 h) in four groups (n = 8) of male Wistar rats: 1) endotoxemia induced by intraperitoneal injection of Escherichia coli lipopolysaccharide, 2) MV without endotoxemia, 3) combination of endotoxemia and MV and 4) sham control. Diaphragm mechanical performance, pro-inflammatory cytokine concentrations (Tumor Necrosis Factor-α, Interleukin-1β, Interleukin-6) in plasma were measured.<h4>Results</h4>Prolonged MV and sepsis independtly reduced maximum diaphragm force (-27%, P = 0.003; -37%, P<0.001; respectively). MV and sepsis acted additively to further decrease diaphragm force (-62%, P<0.001). Similar results were observed for diaphragm kinetics (maximum lengthening velocity -47%, P<0.001). Sepsis and MV reduced diaphragm cross sectional area of type I and IIx fibers, which was further increased by the combination of sepsis and MV (all P<0.05). Sepsis and MV were individually associated with the presence of a robust perimysial inflammatory infiltrate, which was more marked when sepsis and MV were both present (all P<0.05). Sepsis and, to a lesser extent, MV increased proinflammatory cytokine production in plasma and diaphragm (all P<0.05); proinflammatory cytokine expression in plasma was increased further by the combination of sepsis and MV (all P<0.05). Maximum diaphragm force correlated negatively with plasma and diaphragmatic cytokine production (all p<0.05).<h4>Conclusions</h4>Prolonged (12 h) MV exacerbated sepsis-induced decrease in diaphragm performance. Systemic and diaphragmatic overproduction of pro-inflammatory cytokines may contribute to diaphragm weakness. |
| format | Article |
| id | doaj-art-a6cdcbfc01ca42e28a7792316ed570ea |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2018-01-01 |
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| spelling | doaj-art-a6cdcbfc01ca42e28a7792316ed570ea2025-08-20T02:54:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01138e020042910.1371/journal.pone.0200429Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat.Matthieu Le DinhSerge CarreiraJulie ObertGhislaine Gayan-RamirezBruno RiouMaud BeuvinThomas SimilowskiCatherine CoiraultAlexandre Demoule<h4>Background</h4>Short-term mechanical ventilation (MV) protects against sepsis-induced diaphragmatic dysfunction. Prolonged MV induces diaphragmatic dysfunction in non-septic animals, but few reports describe the effects of prolonged MV in sepsis. We hypothesized that prolonged MV is not protective but worsens the diaphragmatic dysfunction induced by a mild sepsis, because MV and sepsis share key signaling mechanisms, such as cytokine upregulation.<h4>Method</h4>We studied the impact of prolonged MV (12 h) in four groups (n = 8) of male Wistar rats: 1) endotoxemia induced by intraperitoneal injection of Escherichia coli lipopolysaccharide, 2) MV without endotoxemia, 3) combination of endotoxemia and MV and 4) sham control. Diaphragm mechanical performance, pro-inflammatory cytokine concentrations (Tumor Necrosis Factor-α, Interleukin-1β, Interleukin-6) in plasma were measured.<h4>Results</h4>Prolonged MV and sepsis independtly reduced maximum diaphragm force (-27%, P = 0.003; -37%, P<0.001; respectively). MV and sepsis acted additively to further decrease diaphragm force (-62%, P<0.001). Similar results were observed for diaphragm kinetics (maximum lengthening velocity -47%, P<0.001). Sepsis and MV reduced diaphragm cross sectional area of type I and IIx fibers, which was further increased by the combination of sepsis and MV (all P<0.05). Sepsis and MV were individually associated with the presence of a robust perimysial inflammatory infiltrate, which was more marked when sepsis and MV were both present (all P<0.05). Sepsis and, to a lesser extent, MV increased proinflammatory cytokine production in plasma and diaphragm (all P<0.05); proinflammatory cytokine expression in plasma was increased further by the combination of sepsis and MV (all P<0.05). Maximum diaphragm force correlated negatively with plasma and diaphragmatic cytokine production (all p<0.05).<h4>Conclusions</h4>Prolonged (12 h) MV exacerbated sepsis-induced decrease in diaphragm performance. Systemic and diaphragmatic overproduction of pro-inflammatory cytokines may contribute to diaphragm weakness.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0200429&type=printable |
| spellingShingle | Matthieu Le Dinh Serge Carreira Julie Obert Ghislaine Gayan-Ramirez Bruno Riou Maud Beuvin Thomas Similowski Catherine Coirault Alexandre Demoule Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat. PLoS ONE |
| title | Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat. |
| title_full | Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat. |
| title_fullStr | Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat. |
| title_full_unstemmed | Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat. |
| title_short | Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat. |
| title_sort | prolonged mechanical ventilation worsens sepsis induced diaphragmatic dysfunction in the rat |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0200429&type=printable |
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