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-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.