• Konstantin A Krychtiuk, Lukas Watzke, Christoph Kaun, Elisabeth Buchberger, Renate Hofer-Warbinek, Svitlana Demyanets, Julia Pisoni, Stefan P Kastl, Sabine Rauscher, Marion Gröger, Arezu Aliabadi, Andreas Zuckermann, Gerald Maurer, Rainer de Martin, Kurt Huber, Johann Wojta, and Walter S Speidl.
• Johann Wojta, PhD, Department of Internal Medicine II, Medical University of Vienna, Austria, Tel.: +43 1 4040073500, Fax: +43 1 4040073586, E-mail: johann.wojta@meduniwien.ac.at.
• Thromb Haemostasis. 2015 Feb 1; 113 (2): 350-62.

AbstractLevosimendan is a positive inotropic drug for the treatment of acute decompensated heart failure (HF). Clinical trials showed that levosimendan was particularly effective in HF due to myocardial infarction. Myocardial necrosis induces a strong inflammatory response, involving chemoattractants guiding polymorphonuclear neutrophils (PMN) into the infarcted myocardial tissue. Our aim was to examine whether levosimendan exhibits anti-inflammatory effects on human adult cardiac myocytes (HACM) and human heart microvascular endothelial cells (HHMEC). Cardiac myocytes and endothelial cells were stimulated with interleukin-1β (IL)-1β (200 U/ml) and treated with levosimendan (0.1-10 µM) for 2-48 hours. IL-1β strongly induced expression of IL-6 and IL-8 in HACM and E-selectin and intercellular adhesion molecule-1 (ICAM-1) in HHMEC and human umbilical vein endothelial cells (HUVEC). Treatment with levosimendan strongly attenuated IL-1β-induced expression of IL-6 and IL-8 in HACM as well as E-selectin and ICAM-1 in ECs. Levosimendan treatment further reduced adhesion of PMN to activated endothelial cells under both static and flow conditions by approximately 50 %. Incubation with 5-hydroxydecanoic acid, a selective blocker of mitochondrial ATP-dependent potassium channels, partly abolished the above seen anti-inflammatory effects. Additionally, levosimendan strongly diminished IL-1β-induced reactive oxygen species and nuclear factor-κB (NF-κB) activity through inhibition of S536 phosphorylation. In conclusion, levosimendan exhibits anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro. These findings could explain, at least in part, the beneficial effects of levosimendan after myocardial infarction.

55 keywords...

hide…