No beneficial effects of levosimendan in acute porcine endotoxaemia

Chew, Michelle; Hawthorne, Wayne J.; Bendall, Jason C; Whereat, Sarah; Huang, Stephen; Ting, Iris; Simond, Denbigh; McLean, Anthony S.

doi:10.1111/j.1399-6576.2011.02436.x

Cited by 10 publications

(5 citation statements)

References 30 publications

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“…In the present study, levosimendan did not attenuate the proinflammatory response to endotoxemia and MV in either plasma or the diaphragm (Figures 3 and 4 ). The lack of effect of levosimendan on plasma inflammation after levosimendan exposure is in line with previous studies [ 45 , 46 ]. In apparent contrast, in experimental sepsis induced by cecal ligation and incision, levosimendan did reduce high plasma levels of IL-1β [ 24 ].…”

Section: Discussionsupporting

confidence: 92%

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

et al. 2015

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IntroductionControlled 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.MethodsThree 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.ResultsMechanical 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.ConclusionsMechanical 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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Section: Discussionsupporting

confidence: 92%

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

et al. 2015

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“…Additionally, it was found that levosimendan increased coronary blood flow 19 . In contrast to these beneficial studies, negative results were described in a study with levosimendan in endotoxin‐induced PH in rats 22 . In this experiment, no improvement in RV or LV function was found and levosimendan was associated with hyperlactatemia, acidosis, and an increase in plasma proinflammatory cytokines.…”

Section: Levosimendan In Phmentioning

confidence: 79%

Levosimendan in pulmonary hypertension and right heart failure

Hansen¹,

Andersen²,

Nielsen‐Kudsk³

2018

Pulm. circ.

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Pulmonary hypertension is a multifactorial disease with a high morbidity and mortality. Right ventricular function is the most important predictor of morbidity and mortality in patients suffering from pulmonary hypertension, but currently there are no approved treatments directly supporting the failing right ventricle. Levosimendan is a calcium sensitizing agent with inotropic, pulmonary vasodilatory, and cardioprotective properties. Given its pharmacodynamic profile, levosimendan could be a potential novel agent for the treatment of right ventricular failure caused by pulmonary hypertension. The aim of this review is to provide an overview of the current knowledge on the effects of levosimendan in pulmonary hypertension and right heart failure.

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“…The effects of levosimendan on outcome are controversial, particularly in sepsis [128]. However, in certain situations, it may be advantageous; for example, levosimendan is a Ca 2+ sensitizer and inodilator, with immunomodulatory and antiapoptotic properties.…”

Section: Inotropic Agentsmentioning

confidence: 97%