Levosimendan

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

Z. Papp, I. Édes, Sonja Fruhwald, Stefan G. De Hert, Markku Salmenperä, Heli Leppikangas, Alexandre Mebazaa, Giovanni Landoni, Elena Grossini, Philippe Caimmi, Andrea Morelli, Fabio Guarracino, Robert H G Schwinger, Sven Meyer, Lars Algotsson, Bernt Gerhard Wikström, Kirsten Jörgensen, Gerasimos Filippatos, John T. Parissis, Martín J García González & 5 others Alexander Parkhomenko, Mehmet Birhan Yilmaz, Matti Kivikko, Piero Pollesello, Ferenc Follath

Research output: Contribution to journalArticle

145 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)82-87
Number of pages6
JournalInternational Journal of Cardiology
Volume159
Issue number2
DOIs
Publication statusPublished - Aug 23 2012

Fingerprint

Adenosine Triphosphate
Pharmacology
Troponin C
Drug Receptors
Myofibrils
Phosphoric Diester Hydrolases
Vasodilator Agents
Drug Interactions
Smooth Muscle Myocytes
Mitochondria
Protein Isoforms
simendan
N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide

Keywords

  • Ca-sensitization
  • Cardioprotection
  • Levosimendan
  • Mechanism of action
  • Positive inotropy
  • Vasodilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Levosimendan : Molecular mechanisms and clinical implications: Consensus of experts on the mechanisms of action of levosimendan. / Papp, Z.; Édes, I.; Fruhwald, Sonja; De Hert, Stefan G.; Salmenperä, Markku; Leppikangas, Heli; Mebazaa, Alexandre; Landoni, Giovanni; Grossini, Elena; Caimmi, Philippe; Morelli, Andrea; Guarracino, Fabio; Schwinger, Robert H G; Meyer, Sven; Algotsson, Lars; Wikström, Bernt Gerhard; Jörgensen, Kirsten; Filippatos, Gerasimos; Parissis, John T.; González, Martín J García; Parkhomenko, Alexander; Yilmaz, Mehmet Birhan; Kivikko, Matti; Pollesello, Piero; Follath, Ferenc.

In: International Journal of Cardiology, Vol. 159, No. 2, 23.08.2012, p. 82-87.

Research output: Contribution to journalArticle

Papp, Z, Édes, I, Fruhwald, S, De Hert, SG, Salmenperä, M, Leppikangas, H, Mebazaa, A, Landoni, G, Grossini, E, Caimmi, P, Morelli, A, Guarracino, F, Schwinger, RHG, Meyer, S, Algotsson, L, Wikström, BG, Jörgensen, K, Filippatos, G, Parissis, JT, González, MJG, Parkhomenko, A, Yilmaz, MB, Kivikko, M, Pollesello, P & Follath, F 2012, 'Levosimendan: Molecular mechanisms and clinical implications: Consensus of experts on the mechanisms of action of levosimendan', International Journal of Cardiology, vol. 159, no. 2, pp. 82-87. https://doi.org/10.1016/j.ijcard.2011.07.022
Papp, Z. ; Édes, I. ; Fruhwald, Sonja ; De Hert, Stefan G. ; Salmenperä, Markku ; Leppikangas, Heli ; Mebazaa, Alexandre ; Landoni, Giovanni ; Grossini, Elena ; Caimmi, Philippe ; Morelli, Andrea ; Guarracino, Fabio ; Schwinger, Robert H G ; Meyer, Sven ; Algotsson, Lars ; Wikström, Bernt Gerhard ; Jörgensen, Kirsten ; Filippatos, Gerasimos ; Parissis, John T. ; González, Martín J García ; Parkhomenko, Alexander ; Yilmaz, Mehmet Birhan ; Kivikko, Matti ; Pollesello, Piero ; Follath, Ferenc. / Levosimendan : Molecular mechanisms and clinical implications: Consensus of experts on the mechanisms of action of levosimendan. In: International Journal of Cardiology. 2012 ; Vol. 159, No. 2. pp. 82-87.
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