TY - JOUR
T1 - Levosimendan: Molecular mechanisms and clinical implications Consensus of experts on the mechanisms of action of levosimendan
AU - Papp, Zoltan
AU - Edes, Istvan
AU - Fruhwald, Sonja
AU - De Hert, Stefan G.
AU - Salmenpera, Markku
AU - Leppikangas, Heli
AU - Mebazaa, Alexandre
AU - Landoni, Giovanni
AU - Grossini, Elena
AU - Caimmi, Philippe
AU - Morelli, Andrea
AU - Guarracino, Fabio
AU - Schwinger, Robert H. G.
AU - Meyer, Sven
AU - Algotsson, Lars
AU - Wikstrom, Bernt Gerhard
AU - Jorgensen, Kirsten
AU - Filippatos, Gerasimos
AU - Parissis, John T.
AU - Garcia Gonzalez, Martin J.
AU - Parkhomenko, Alexander
AU - Yilmaz, Mehmet Birhan
AU - Kivikko, Matti
AU - Pollesello, Piero
AU - Follath, Ferenc
PY - 2012
Y1 - 2012
N2 - The molecular background of the Ca2+-sensitizing effect of levosimendan relates to its specific interaction with the Ca2+-sensor troponin C molecule in the cardiac myofilaments. Over the years, significant preclinical and clinical evidence has accumulated and revealed a variety of beneficial pleiotropic effects of levosimendan and of its long-lived metabolite, OR-1896. First of all, activation of ATP-sensitive sarcolemmal K+ channels of smooth muscle cells appears as a powerful vasodilator mechanism. Additionally, activation of ATP-sensitive K+ channels in the mitochondria potentially extends the range of cellular actions towards the modulation of mitochondrial ATP production and implicates a pharmacological mechanism for cardioprotection. Finally, it has become evident, that levosimendan possesses an isoform-selective phosphodiesterase-inhibitory effect. Interpretation of the complex mechanism of levosimendan action requires that all potential pharmacological interactions are analyzed carefully in the framework of the currently available evidence. These data indicate that the cardiovascular effects of levosimendan are exerted via more than an isolated drug-receptor interaction, and involve favorable energetic and neurohormonal changes that are unique in comparison to other types of inodilators. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
AB - The molecular background of the Ca2+-sensitizing effect of levosimendan relates to its specific interaction with the Ca2+-sensor troponin C molecule in the cardiac myofilaments. Over the years, significant preclinical and clinical evidence has accumulated and revealed a variety of beneficial pleiotropic effects of levosimendan and of its long-lived metabolite, OR-1896. First of all, activation of ATP-sensitive sarcolemmal K+ channels of smooth muscle cells appears as a powerful vasodilator mechanism. Additionally, activation of ATP-sensitive K+ channels in the mitochondria potentially extends the range of cellular actions towards the modulation of mitochondrial ATP production and implicates a pharmacological mechanism for cardioprotection. Finally, it has become evident, that levosimendan possesses an isoform-selective phosphodiesterase-inhibitory effect. Interpretation of the complex mechanism of levosimendan action requires that all potential pharmacological interactions are analyzed carefully in the framework of the currently available evidence. These data indicate that the cardiovascular effects of levosimendan are exerted via more than an isolated drug-receptor interaction, and involve favorable energetic and neurohormonal changes that are unique in comparison to other types of inodilators. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
KW - Levosimendan
KW - Mechanism of action
KW - Ca2+-sensitization
KW - Positive
KW - inotropy
KW - Vasodilation
KW - Cardioprotection
U2 - 10.1016/j.ijcard.2011.07.022
DO - 10.1016/j.ijcard.2011.07.022
M3 - Review article
C2 - 21784540
SN - 0167-5273
VL - 159
SP - 82
EP - 87
JO - International Journal of Cardiology
JF - International Journal of Cardiology
IS - 2
ER -