Effect of levosimendan and milrinone on regional myocardial ischemia/reperfusion-induced arrhythmias in dogs.
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.
Papp
Julius Gy
JG
Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, University of Szeged, Szeged, Hungary. Papp@phcol.szote.u-szeged.hu
Pollesello
Piero
P
Varró
András F
AF
Végh
Agnes S
AS
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
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D020105:Milrinone