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Open Access 01-12-2015 | Research

Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice

Authors: Willem-Jan M Schellekens, Hieronymus WH van Hees, Marianne Linkels, PN Richard Dekhuijzen, Gert Jan Scheffer, Johannes G van der Hoeven, Leo MA Heunks

Published in: Critical Care | Issue 1/2015

Abstract

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.

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Title: Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice
Authors: Willem-Jan M Schellekens
Hieronymus WH van Hees
Marianne Linkels
PN Richard Dekhuijzen
Gert Jan Scheffer
Johannes G van der Hoeven
Leo MA Heunks
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/s13054-015-0798-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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