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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...

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Detalles Bibliográficos
Autores principales: Schellekens, Willem-Jan M, van Hees, Hieronymus WH, Linkels, Marianne, Dekhuijzen, PN Richard, Scheffer, Gert Jan, van der Hoeven, Johannes G, Heunks, Leo MA
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
Descripción
Sumario: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.