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Biol Res Nurs. 2019 Jul 4:1099800419861694. doi: 10.1177/1099800419861694. [Epub ahead of print]

Effects of Levosimendan on Inflammation and Oxidative Stress Pathways in a Lipopolysaccharide-Stimulated Human Endothelial Cell Model.

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1 Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, School of Nursing, University of Santiago de Compostela, Santiago de Compostela, Spain.
2 Health Research Institute of Santiago de Compostela (IDIS), Galician Health System, Clinical University Hospital, Santiago de Compostela, Spain.
3 Critical Care, Orion Pharma, Espoo, Finland.
4 Department of Surgery, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.


Levosimendan is a myocardial Ca2+ sensitizer and opener of ATP-dependent potassium channels with inotropic, vasodilating, and cardioprotective properties. It was originally developed for the treatment of acute decompensated heart failure, but its complex mechanism of action means that it could also play a role in organ protection in response to infection. Using an in vitro approach, we explored whether levosimendan administration influenced cell responses to lipopolysaccharide (LPS). Primary human umbilical vein endothelial cells were stimulated with 1 µg/ml LPS from Escherichia coli (E. coli). Cells were treated with levosimendan at 0, 0.1, 1, or 10 µM 3 hr later. Samples were taken 24 hr after treatment to measure cell necrosis, apoptosis, pro-inflammatory mediators (interleukin 6 [IL-6] and toll-like receptor 4 [TLR4]), and oxidative stress (total reactive oxygen species/reactive nitrogen species [ROS/RNS]). Levosimendan at 1 and 10 µM protected against LPS-induced endothelial cell death and reduced TLR4 expression (p < .05). All doses reduced levels of IL-6 and ROS/RNS (p < .05). Findings suggest that levosimendan may exert protective effects against endothelial cell death in this model via attenuation of inflammation and oxidative stress pathways. Future studies might explore the potential beneficial role of levosimendan in modulating molecular mechanisms triggered by infections.


TLR4; cytoprotection; inflammation; levosimendan; oxidative stress


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