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Levosimendan: Molecular mechanisms and clinical implications Consensus of experts on the mechanisms of action of levosimendan

Papp, Zoltan; Edes, Istvan; Fruhwald, Sonja; De Hert, Stefan G.; Salmenpera, Markku; Leppikangas, Heli; Mebazaa, Alexandre; Landoni, Giovanni; Grossini, Elena and Caimmi, Philippe, et al. (2012) In International Journal of Cardiology 159(2). p.82-87
Abstract
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.... (More)
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. (Less)
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keywords
Levosimendan, Mechanism of action, Ca2+-sensitization, Positive, inotropy, Vasodilation, Cardioprotection
in
International Journal of Cardiology
volume
159
issue
2
pages
82 - 87
publisher
Elsevier
external identifiers
  • wos:000307827100011
  • scopus:84864990939
ISSN
0167-5273
DOI
10.1016/j.ijcard.2011.07.022
language
English
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f19e3455-c6ed-48b9-86a0-eee2844315ed (old id 3055789)
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2012-10-05 07:15:22
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2017-11-19 03:21:17
@article{f19e3455-c6ed-48b9-86a0-eee2844315ed,
  abstract     = {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.},
  author       = {Papp, Zoltan and Edes, Istvan and Fruhwald, Sonja and De Hert, Stefan G. and Salmenpera, Markku and Leppikangas, Heli and Mebazaa, Alexandre and Landoni, Giovanni and Grossini, Elena and Caimmi, Philippe and Morelli, Andrea and Guarracino, Fabio and Schwinger, Robert H. G. and Meyer, Sven and Algotsson, Lars and Wikstrom, Bernt Gerhard and Jorgensen, Kirsten and Filippatos, Gerasimos and Parissis, John T. and Garcia Gonzalez, Martin J. and Parkhomenko, Alexander and Yilmaz, Mehmet Birhan and Kivikko, Matti and Pollesello, Piero and Follath, Ferenc},
  issn         = {0167-5273},
  keyword      = {Levosimendan,Mechanism of action,Ca2+-sensitization,Positive,inotropy,Vasodilation,Cardioprotection},
  language     = {eng},
  number       = {2},
  pages        = {82--87},
  publisher    = {Elsevier},
  series       = {International Journal of Cardiology},
  title        = {Levosimendan: Molecular mechanisms and clinical implications Consensus of experts on the mechanisms of action of levosimendan},
  url          = {http://dx.doi.org/10.1016/j.ijcard.2011.07.022},
  volume       = {159},
  year         = {2012},
}