title: Effect of levosimendan and milrinone on regional myocardial ischemia/reperfusion-induced arrhythmias in dogs.
abstract: 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 micromol/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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, University of Szeged, Szeged, Hungary. Papp@phcol.szote.u-szeged.hu
authors.forename: Julius Gy
authors.initials: JG
authors.lastname: Papp
authors.forename: Piero
authors.initials: P
authors.lastname: Pollesello
authors.forename: András F
authors.initials: AF
authors.lastname: Varró
authors.forename: Agnes S
authors.initials: AS
authors.lastname: Végh
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000627:therapeutic use*; D008297:Male; D020105:Milrinone / Q000627:therapeutic use*; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D011724:Pyridazines / Q000627:therapeutic use*; D000077464:Simendan; D016276:Ventricular Function
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D020105:Milrinone