Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat.
BACKGROUND: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 w...
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doaj-a6cdcbfc01ca42e28a7792316ed570ea2020-11-24T21:35:37ZengPublic 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 DemouleBACKGROUND: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. METHOD: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. RESULTS: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). CONCLUSIONS:Prolonged (12 h) MV exacerbated sepsis-induced decrease in diaphragm performance. Systemic and diaphragmatic overproduction of pro-inflammatory cytokines may contribute to diaphragm weakness.http://europepmc.org/articles/PMC6070213?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthieu Le Dinh Serge Carreira Julie Obert Ghislaine Gayan-Ramirez Bruno Riou Maud Beuvin Thomas Similowski Catherine Coirault Alexandre Demoule |
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 |
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 |
title |
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_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_sort |
prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2018-01-01 |
description |
BACKGROUND: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. METHOD: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. RESULTS: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). CONCLUSIONS:Prolonged (12 h) MV exacerbated sepsis-induced decrease in diaphragm performance. Systemic and diaphragmatic overproduction of pro-inflammatory cytokines may contribute to diaphragm weakness. |
url |
http://europepmc.org/articles/PMC6070213?pdf=render |
work_keys_str_mv |
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