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Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan.

Abstract：

:The molecular background of the Ca(2+)-sensitizing effect of levosimendan relates to its specific interaction with the Ca(2+)-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.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

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 RH,Meyer S,Algotsson L,Wikström BG,Jörgensen K,Filippatos G,Parissis JT,Gonzále

doi

10.1016/j.ijcard.2011.07.022

subject

Has Abstract

pub_date

2012-08-23 00:00:00

pages

82-7

issue

2

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(11)00708-X

journal_volume

159

pub_type

杂志文章,评审

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