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Journal of Cardiovascular Pharmacology and Therapeutics
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Effect of Levosimendan and Milrinone on Regional Myocardial Ischemia/Reperfusion-Induced Arrhythmias in Dogs

Julius Gy. Papp, MD, PhD, DSc

Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, University of Szeged, Szeged, Hungary, Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary

Piero Pollesello, PhD

Cardiovascular and Critical Care, Orion Pharma, Espoo, Finland, Papp{at}phcol.szote.u-szeged.hu

András F. Varró, MD, PhD, DSc

Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, University of Szeged, Szeged, Hungary

Ágnes S. Végh, PhD, DSc

Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, University of Szeged, Szeged, Hungary

Phosphodiesterase inhibitors as inodilators in heart failure are associated with promotion of arrhythmias. Calcium sensitizers have been proposed for the treatment of severe decompensated heart failure. The effect of levosimendan, a calcium sensitizer, and milrinone, a phosphodiesterase inhibitor, on ventricular arrhythmias was compared in a model of acute regional myocardial ischemia and reperfusion. The left anterior descending coronary artery in dogs was occluded for 25 minutes, followed by reperfusion. The 2 drugs were administered in a hemodynamically equieffective dose (0.1 µmol/kg) 10 minutes before coronary occlusion. Levosimendan, but not milrinone, significantly attenuated the pronounced increase in the number of ventricular premature beats (-63%), tachycardia (-50%), fibrillation (-70%), and inhomogeneity of ventricular electrical activation. Levosimendan significantly improved the overall survival rate. Levosimendan has a more beneficial profile than milrinone regarding the development of ventricular arrhythmias during and after regional myocardial ischemia

Key Words: myocardial ischemia/reperfusion • ventricular arrhythmias • levosimendan

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 11, No. 2, 129-135 (2006)
DOI: 10.1177/1074248406289286
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