Levosimendan: Molecular mechanisms and clinical implications Consensus of experts on the mechanisms of action of levosimendan
Tarih
2012Yazar
Papp, ZoltanEdes, Istvan
Fruhwald, Sonja
De Hert, Stefan G.
Salmenpera, Markku
Leppikangas, Heli
Mebazaa, Alexandre
Landoni, Giovanni
Grossini, Elena
Caimmi, Philippe
Morelli, Andrea
Guarracino, Fabio
Schwinger, Robert H. G.
Meyer, Sven
Algotsson, Lars
Wikstrom, Bernt Gerhard
Jorgensen, Kirsten
Filippatos, Gerasimos
Parissis, John T.
Garcia Gonzalez, Martin J.
Parkhomenko, Alexander
Yilmaz, Mehmet Birhan
Kivikko, Matti
Pollesello, Piero
Follath, Ferenc
Üst veri
Tüm öğe kaydını gösterÖzet
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.
Kaynak
INTERNATIONAL JOURNAL OF CARDIOLOGYCilt
159Sayı
2Koleksiyonlar
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