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...

Full description

Saved in:
Bibliographic Details
Main Authors: Matthieu Le Dinh, Serge Carreira, Julie Obert, Ghislaine Gayan-Ramirez, Bruno Riou, Maud Beuvin, Thomas Similowski, Catherine Coirault, Alexandre Demoule
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0200429&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850045018188808192
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
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
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
work_keys_str_mv AT matthieuledinh prolongedmechanicalventilationworsenssepsisinduceddiaphragmaticdysfunctionintherat
AT sergecarreira prolongedmechanicalventilationworsenssepsisinduceddiaphragmaticdysfunctionintherat
AT julieobert prolongedmechanicalventilationworsenssepsisinduceddiaphragmaticdysfunctionintherat
AT ghislainegayanramirez prolongedmechanicalventilationworsenssepsisinduceddiaphragmaticdysfunctionintherat
AT brunoriou prolongedmechanicalventilationworsenssepsisinduceddiaphragmaticdysfunctionintherat
AT maudbeuvin prolongedmechanicalventilationworsenssepsisinduceddiaphragmaticdysfunctionintherat
AT thomassimilowski prolongedmechanicalventilationworsenssepsisinduceddiaphragmaticdysfunctionintherat
AT catherinecoirault prolongedmechanicalventilationworsenssepsisinduceddiaphragmaticdysfunctionintherat
AT alexandredemoule prolongedmechanicalventilationworsenssepsisinduceddiaphragmaticdysfunctionintherat