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Mechanical ventilation causes diaphragm dysfunction in newborn lambs

BACKGROUND: Diaphragm weakness occurs rapidly in adult animals treated with mechanical ventilation (MV), but the effects of MV on the neonatal diaphragm have not been determined. Furthermore, it is unknown whether co-existent lung disease exacerbates ventilator-induced diaphragmatic dysfunction (VID...

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Autores principales: Liang, Feng, Emeriaud, Guillaume, Rassier, Dilson E., Shang, Dong, Gusev, Ekaterina, Hussain, Sabah N. A., Sage, Michael, Crulli, Benjamin, Fortin-Pellerin, Etienne, Praud, Jean-Paul, Petrof, Basil J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469194/
https://www.ncbi.nlm.nih.gov/pubmed/30992039
http://dx.doi.org/10.1186/s13054-019-2409-6
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author Liang, Feng
Emeriaud, Guillaume
Rassier, Dilson E.
Shang, Dong
Gusev, Ekaterina
Hussain, Sabah N. A.
Sage, Michael
Crulli, Benjamin
Fortin-Pellerin, Etienne
Praud, Jean-Paul
Petrof, Basil J.
author_facet Liang, Feng
Emeriaud, Guillaume
Rassier, Dilson E.
Shang, Dong
Gusev, Ekaterina
Hussain, Sabah N. A.
Sage, Michael
Crulli, Benjamin
Fortin-Pellerin, Etienne
Praud, Jean-Paul
Petrof, Basil J.
author_sort Liang, Feng
collection PubMed
description BACKGROUND: Diaphragm weakness occurs rapidly in adult animals treated with mechanical ventilation (MV), but the effects of MV on the neonatal diaphragm have not been determined. Furthermore, it is unknown whether co-existent lung disease exacerbates ventilator-induced diaphragmatic dysfunction (VIDD). We investigated the impact of MV (mean duration = 7.65 h), either with or without co-existent respiratory failure caused by surfactant deficiency, on the development of VIDD in newborn lambs. METHODS: Newborn lambs (1–4 days) were assigned to control (CTL, non-ventilated), mechanically ventilated (MV), and MV + experimentally induced surfactant deficiency (MV+SD) groups. Immunoblotting and quantitative PCR assessed inflammatory signaling, the ubiquitin-proteasome system, autophagy, and oxidative stress. Immunostaining for myosin heavy chain (MyHC) isoforms and quantitative morphometry evaluated diaphragm atrophy. Contractile function of the diaphragm was determined in isolated myofibrils ex vivo. RESULTS: Equal decreases (25–30%) in myofibrillar force generation were found in MV and MV+SD diaphragms compared to CTL. In comparison to CTL, both MV and MV+SD diaphragms also demonstrated increased STAT3 transcription factor phosphorylation. Ubiquitin-proteasome system (Atrogin1 and MuRF1) transcripts and autophagy indices (Gabarapl1 transcripts and the ratio of LC3B-II/LC3B-I protein) were greater in MV+SD relative to MV alone, but fiber type atrophy was not observed in any group. Protein carbonylation and 4-hydroxynonenal levels (indices of oxidative stress) also did not differ among groups. CONCLUSIONS: In newborn lambs undergoing controlled MV, there is a rapid onset of diaphragm dysfunction consistent with VIDD. Superimposed lung injury caused by surfactant deficiency did not influence the severity of early diaphragm weakness. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-019-2409-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-64691942019-04-23 Mechanical ventilation causes diaphragm dysfunction in newborn lambs Liang, Feng Emeriaud, Guillaume Rassier, Dilson E. Shang, Dong Gusev, Ekaterina Hussain, Sabah N. A. Sage, Michael Crulli, Benjamin Fortin-Pellerin, Etienne Praud, Jean-Paul Petrof, Basil J. Crit Care Research BACKGROUND: Diaphragm weakness occurs rapidly in adult animals treated with mechanical ventilation (MV), but the effects of MV on the neonatal diaphragm have not been determined. Furthermore, it is unknown whether co-existent lung disease exacerbates ventilator-induced diaphragmatic dysfunction (VIDD). We investigated the impact of MV (mean duration = 7.65 h), either with or without co-existent respiratory failure caused by surfactant deficiency, on the development of VIDD in newborn lambs. METHODS: Newborn lambs (1–4 days) were assigned to control (CTL, non-ventilated), mechanically ventilated (MV), and MV + experimentally induced surfactant deficiency (MV+SD) groups. Immunoblotting and quantitative PCR assessed inflammatory signaling, the ubiquitin-proteasome system, autophagy, and oxidative stress. Immunostaining for myosin heavy chain (MyHC) isoforms and quantitative morphometry evaluated diaphragm atrophy. Contractile function of the diaphragm was determined in isolated myofibrils ex vivo. RESULTS: Equal decreases (25–30%) in myofibrillar force generation were found in MV and MV+SD diaphragms compared to CTL. In comparison to CTL, both MV and MV+SD diaphragms also demonstrated increased STAT3 transcription factor phosphorylation. Ubiquitin-proteasome system (Atrogin1 and MuRF1) transcripts and autophagy indices (Gabarapl1 transcripts and the ratio of LC3B-II/LC3B-I protein) were greater in MV+SD relative to MV alone, but fiber type atrophy was not observed in any group. Protein carbonylation and 4-hydroxynonenal levels (indices of oxidative stress) also did not differ among groups. CONCLUSIONS: In newborn lambs undergoing controlled MV, there is a rapid onset of diaphragm dysfunction consistent with VIDD. Superimposed lung injury caused by surfactant deficiency did not influence the severity of early diaphragm weakness. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-019-2409-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-04-16 /pmc/articles/PMC6469194/ /pubmed/30992039 http://dx.doi.org/10.1186/s13054-019-2409-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Liang, Feng
Emeriaud, Guillaume
Rassier, Dilson E.
Shang, Dong
Gusev, Ekaterina
Hussain, Sabah N. A.
Sage, Michael
Crulli, Benjamin
Fortin-Pellerin, Etienne
Praud, Jean-Paul
Petrof, Basil J.
Mechanical ventilation causes diaphragm dysfunction in newborn lambs
title Mechanical ventilation causes diaphragm dysfunction in newborn lambs
title_full Mechanical ventilation causes diaphragm dysfunction in newborn lambs
title_fullStr Mechanical ventilation causes diaphragm dysfunction in newborn lambs
title_full_unstemmed Mechanical ventilation causes diaphragm dysfunction in newborn lambs
title_short Mechanical ventilation causes diaphragm dysfunction in newborn lambs
title_sort mechanical ventilation causes diaphragm dysfunction in newborn lambs
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469194/
https://www.ncbi.nlm.nih.gov/pubmed/30992039
http://dx.doi.org/10.1186/s13054-019-2409-6
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