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

Papp Z., Edes I., Fruhwald S., De Hert S. G., Salmenpera M., Leppikangas H., ...More

INTERNATIONAL JOURNAL OF CARDIOLOGY, vol.159, no.2, pp.82-87, 2012 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 159 Issue: 2
  • Publication Date: 2012
  • Doi Number: 10.1016/j.ijcard.2011.07.022
  • Journal Name: INTERNATIONAL JOURNAL OF CARDIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.82-87
  • Keywords: Levosimendan, Mechanism of action, Ca2+-sensitization, Positive inotropy, Vasodilation, Cardioprotection, ADVANCED HEART-FAILURE, CARDIAC TROPONIN-C, GUINEA-PIG HEART, PERCUTANEOUS CORONARY INTERVENTION, RANDOMIZED CONTROLLED-TRIALS, LEFT-VENTRICULAR DYSFUNCTION, ACUTE MYOCARDIAL-INFARCTION, FAILING HUMAN MYOCARDIUM, IMPROVES RENAL-FUNCTION, K-ATP CHANNELS
  • Dokuz Eylül University Affiliated: No

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.