Cargando…
Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice
INTRODUCTION: Controlled mechanical ventilation and endotoxemia are associated with diaphragm muscle atrophy and dysfunction. Oxidative stress and activation of inflammatory pathways are involved in the pathogenesis of diaphragmatic dysfunction. Levosimendan, a cardiac inotrope, has been reported to...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355991/ https://www.ncbi.nlm.nih.gov/pubmed/25888356 http://dx.doi.org/10.1186/s13054-015-0798-8 |
_version_ | 1782360938795499520 |
---|---|
author | Schellekens, Willem-Jan M van Hees, Hieronymus WH Linkels, Marianne Dekhuijzen, PN Richard Scheffer, Gert Jan van der Hoeven, Johannes G Heunks, Leo MA |
author_facet | Schellekens, Willem-Jan M van Hees, Hieronymus WH Linkels, Marianne Dekhuijzen, PN Richard Scheffer, Gert Jan van der Hoeven, Johannes G Heunks, Leo MA |
author_sort | Schellekens, Willem-Jan M |
collection | PubMed |
description | INTRODUCTION: Controlled mechanical ventilation and endotoxemia are associated with diaphragm muscle atrophy and dysfunction. Oxidative stress and activation of inflammatory pathways are involved in the pathogenesis of diaphragmatic dysfunction. Levosimendan, a cardiac inotrope, has been reported to possess anti-oxidative and anti-inflammatory properties. The aim of the present study was to investigate the effects of levosimendan on markers for diaphragm nitrosative and oxidative stress, inflammation and proteolysis in a mouse model of endotoxemia and mechanical ventilation. METHODS: Three groups were studied: (1) unventilated mice (CON, n =8), (2) mechanically ventilated endotoxemic mice (MV LPS, n =17) and (3) mechanically ventilated endotoxemic mice treated with levosimendan (MV LPS + L, n =17). Immediately after anesthesia (CON) or after 8 hours of mechanical ventilation, blood and diaphragm muscle were harvested for biochemical analysis. RESULTS: Mechanical ventilation and endotoxemia increased expression of inducible nitric oxide synthase (iNOS) mRNA and cytokine levels of interleukin (IL)-1β, IL-6 and keratinocyte-derived chemokine, and decreased IL-10, in the diaphragm; however, they had no effect on protein nitrosylation and 4-hydroxy-2-nonenal protein concentrations. Levosimendan decreased nitrosylated proteins by 10% (P <0.05) and 4-hydroxy-2-nonenal protein concentrations by 13% (P <0.05), but it augmented the rise of iNOS mRNA by 47% (P <0.05). Levosimendan did not affect the inflammatory response in the diaphragm induced by mechanical ventilation and endotoxemia. CONCLUSIONS: Mechanical ventilation in combination with endotoxemia results in systemic and diaphragmatic inflammation. Levosimendan partly decreased markers of nitrosative and oxidative stress, but did not affect the inflammatory response. |
format | Online Article Text |
id | pubmed-4355991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43559912015-03-12 Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice Schellekens, Willem-Jan M van Hees, Hieronymus WH Linkels, Marianne Dekhuijzen, PN Richard Scheffer, Gert Jan van der Hoeven, Johannes G Heunks, Leo MA Crit Care Research INTRODUCTION: Controlled mechanical ventilation and endotoxemia are associated with diaphragm muscle atrophy and dysfunction. Oxidative stress and activation of inflammatory pathways are involved in the pathogenesis of diaphragmatic dysfunction. Levosimendan, a cardiac inotrope, has been reported to possess anti-oxidative and anti-inflammatory properties. The aim of the present study was to investigate the effects of levosimendan on markers for diaphragm nitrosative and oxidative stress, inflammation and proteolysis in a mouse model of endotoxemia and mechanical ventilation. METHODS: Three groups were studied: (1) unventilated mice (CON, n =8), (2) mechanically ventilated endotoxemic mice (MV LPS, n =17) and (3) mechanically ventilated endotoxemic mice treated with levosimendan (MV LPS + L, n =17). Immediately after anesthesia (CON) or after 8 hours of mechanical ventilation, blood and diaphragm muscle were harvested for biochemical analysis. RESULTS: Mechanical ventilation and endotoxemia increased expression of inducible nitric oxide synthase (iNOS) mRNA and cytokine levels of interleukin (IL)-1β, IL-6 and keratinocyte-derived chemokine, and decreased IL-10, in the diaphragm; however, they had no effect on protein nitrosylation and 4-hydroxy-2-nonenal protein concentrations. Levosimendan decreased nitrosylated proteins by 10% (P <0.05) and 4-hydroxy-2-nonenal protein concentrations by 13% (P <0.05), but it augmented the rise of iNOS mRNA by 47% (P <0.05). Levosimendan did not affect the inflammatory response in the diaphragm induced by mechanical ventilation and endotoxemia. CONCLUSIONS: Mechanical ventilation in combination with endotoxemia results in systemic and diaphragmatic inflammation. Levosimendan partly decreased markers of nitrosative and oxidative stress, but did not affect the inflammatory response. BioMed Central 2015-03-02 2015 /pmc/articles/PMC4355991/ /pubmed/25888356 http://dx.doi.org/10.1186/s13054-015-0798-8 Text en © Schellekens et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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 Schellekens, Willem-Jan M van Hees, Hieronymus WH Linkels, Marianne Dekhuijzen, PN Richard Scheffer, Gert Jan van der Hoeven, Johannes G Heunks, Leo MA Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice |
title | Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice |
title_full | Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice |
title_fullStr | Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice |
title_full_unstemmed | Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice |
title_short | Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice |
title_sort | levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355991/ https://www.ncbi.nlm.nih.gov/pubmed/25888356 http://dx.doi.org/10.1186/s13054-015-0798-8 |
work_keys_str_mv | AT schellekenswillemjanm levosimendanaffectsoxidativeandinflammatorypathwaysinthediaphragmofventilatedendotoxemicmice AT vanheeshieronymuswh levosimendanaffectsoxidativeandinflammatorypathwaysinthediaphragmofventilatedendotoxemicmice AT linkelsmarianne levosimendanaffectsoxidativeandinflammatorypathwaysinthediaphragmofventilatedendotoxemicmice AT dekhuijzenpnrichard levosimendanaffectsoxidativeandinflammatorypathwaysinthediaphragmofventilatedendotoxemicmice AT scheffergertjan levosimendanaffectsoxidativeandinflammatorypathwaysinthediaphragmofventilatedendotoxemicmice AT vanderhoevenjohannesg levosimendanaffectsoxidativeandinflammatorypathwaysinthediaphragmofventilatedendotoxemicmice AT heunksleoma levosimendanaffectsoxidativeandinflammatorypathwaysinthediaphragmofventilatedendotoxemicmice |