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Effects of Levosimendan on the Energy Balance: Preclinical and Clinical Evidence

Nieminen, Markku S MD, PhD*; Pollesello, Piero PhD; Vajda, Gusztáv MD; Papp, Zoltán MD, PhD

Journal of Cardiovascular Pharmacology: April 2009 - Volume 53 - Issue 4 - p 302-310
doi: 10.1097/FJC.0b013e31819c9a17
Review Article

Levosimendan is a novel inodilator agent, which enhances myocardial performance without substantial changes in oxygen consumption. The combination of positive inotropic and vasodilator effects of levosimendan relates to its Ca2+-sensitizing and K+ channel opening effects. Levosimendan is one of the best documented pharmacological agents used in the management of acute heart failure syndromes. Interest in levosimendan has recently been renewed owing to its potential in supporting cardiac function in patients with ischemic heart disease and cardiogenic or septic shock. It has been also demonstrated that levosimendan can be used as a bridge therapy for the perioperative phase of cardiac surgery. The ability of levosimendan to improve myocardial function without substantially increasing oxygen consumption may appear paradoxical but is indeed possible via improved efficacy, not only with regard to the effects on the contractile apparatus of the cardiomyocytes but also when its composite hemodynamic effects are considered. The energy balance equation, therefore, should take into account the effect of levosimendan on all energy-consuming and energy-producing paths. Moreover, levosimendan-evoked KATP channel opening may possess favorable effects on mitochondrial adenosine triphosphate synthesis conferring cardioprotection during ischemic insults.

From the *Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland; †Cardiovascular and Critical Care, Orion Pharma, Espoo, Finland; and ‡Division of Clinical Physiology, Institute of Cardiology, University of Debrecen Medical School and Health Science Center, Debrecen, Hungary.

Received for publication October 3, 2008; accepted January 14, 2009.

Supported by a Hungarian research fund (OTKA grant K 68363).

Dr P. Pollesello is employed by Orion Pharma, the manufacturer of levosimendan in Europe.

Z. Papp holds a Bolyai Fellowship of the Hungarian Academy of Sciences. The other authors report no conflicts of interest.

Reprints: Zoltán Papp, MD, PhD, Division of Clinical Physiology, Institute of Cardiology, University of Debrecen Medical School and Health Science Center, H-4028 Debrecen, Móricz Zs. krt. 22, Hungary (e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.