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Crit Care. 2015 Mar 2;19:69. doi: 10.1186/s13054-015-0798-8.

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

Author information

1
Department of Anesthesiology, Radboud University Medical Centre, Postbox 9101, Nijmegen, 6500 HB, the Netherlands. willem-jan.schellekens@radboudumc.nl.
2
Department of Pulmonary Diseases, Radboud University Medical Centre, Postbox 9101, Nijmegen, 6500 HB, the Netherlands. jeroen.vanhees@radboudumc.nl.
3
Department of Pulmonary Diseases, Radboud University Medical Centre, Postbox 9101, Nijmegen, 6500 HB, the Netherlands. marianne.linkels@radboudumc.nl.
4
Department of Pulmonary Diseases, Radboud University Medical Centre, Postbox 9101, Nijmegen, 6500 HB, the Netherlands. richard.dekhuijzen@radboudumc.nl.
5
Department of Anesthesiology, Radboud University Medical Centre, Postbox 9101, Nijmegen, 6500 HB, the Netherlands. gertjan.scheffer@radboudumc.nl.
6
Department of Intensive Care Medicine, Radboud University Medical Centre, Postbox 9101, Nijmegen, 6500 HB, the Netherlands. hans.vanderhoeven@radboudumc.nl.
7
Department of Intensive Care Medicine, Radboud University Medical Centre, Postbox 9101, Nijmegen, 6500 HB, the Netherlands. leo.heunks@radboudumc.nl.

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.

PMID:
25888356
PMCID:
PMC4355991
DOI:
10.1186/s13054-015-0798-8
[Indexed for MEDLINE]
Free PMC Article

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