Levosimendan exerts anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro

Levosimendan 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-1 beta (IL)-1 beta (200 U/ml) and treated with levosimendan (0.1-10 mu M) for 2-48 hours. IL-1 beta 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-1 beta-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-10-induced reactive oxygen species and nuclear factor-kappa B (NF-kappa B) activity through inhibition of 5536 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.