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European Heart Journal Advance Access published online on February 5, 2007
European Heart Journal, doi:10.1093/eurheartj/ehl487
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Levosimendan: Perpetuum mobile?

Stefan Agewall

Division of Cardiology
Aker University Hospital and Faculty of Medicine
University of Oslo
0514 Oslo
Norway
Tel: +47 22 89 46 55
Fax: +47 22 89 42 59
E-mail address: stefan.agewall{at}medisin.uio.no

Dan Atar

Division of Cardiology
Aker University Hospital and Faculty of Medicine
University of Oslo
0514 Oslo
Norway

We read with great interest the well-written review about levosimendan by De Luca et al.1 Levosimendan is certainly an interesting drug that appears to deliver favourable effects in patients with acute heart failure. Numerous studies have demonstrated the positive inotropic action of levosimendan. In 1998, Lilleberg et al.2 published in this journal an interesting article, which is quoted very often in articles dealing with levosimendan. These authors reported that levosimendan increases cardiac output and stroke volume in patients after coronary bypass surgery, neither increasing myocardial oxygen consumption nor changing myocardial substrate utilization. This observation has been accepted as a fact and has not been challenged.

Cardiac excitation–contraction coupling (EC coupling) is an energy-consuming process.3 Changes in cardiac contractile force can be effected at each of three distinct levels: (i) the modulation of intracellular calcium; (ii) the alteration of the contractile protein response to intracellular calcium; and (iii) changes in loading conditions. Of note, regardless at which level of EC coupling levosimendan exerts its action, it will always act at the expense of energy substrate.

Based on these considerations we do believe that a drug which increases myocardial contractility certainly also increases energy consumption, otherwise levosimedan is the driving force of a cardiac ‘perpetuum mobile’.

References

  1. De Luca L, Colucci WS, Nieminen M, Massie BM, Gheorghiade M. (2006) Evidence-based use of levosimedan in different clinical settings. Eur Heart J 27:1908–1920.[Abstract/Free Full Text]
  2. Lilleberg J, Nieminen MS, Akkila J, Heikkila L, Kuitunen A, Lehtonen L, Verkkala K, Mattila S, Salmenpera M. (1998) Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting. Eur Heart J 19:660–668.[Abstract/Free Full Text]
  3. Bers DM. (1991) Excitation-Contraction Coupling and Cardiac Contractile Force(Kluwer Academic Publishers, Dordrecht, NL).

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This Article
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ehl487v1
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Right arrow Articles by Agewall, S.
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