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Reduction of myocardial infarct size by dronedarone in pigs--a pleiotropic action?Skyschally A; Heusch GCardiovasc Drugs Ther 2011[Jun]; 25 (3): 197-201PURPOSE: Dronedarone is a first-line drug to prevent the recurrence of atrial fibrillation according to ESC guidelines. In the recent ATHENA trial, dronedarone reduced mortality and also hospitalization for acute coronary syndrome in patients with atrial fibrillation. This beneficial effect suggests that dronedarone might have also an impact on events associated with ischemia/reperfusion injury. METHODS: Fourteen anesthetized pigs received either dronedarone (2.5 mg/kg) or placebo. Effects of dronedarone on heart rate and blood pressure were reversed by atrial pacing and aortic constriction before pigs were subjected to 90 min regional low-flow myocardial ischemia and 2 h reperfusion. Regional myocardial blood flow was measured with microspheres and infarct size determined by TTC staining. RESULTS: With comparable heart rate and left ventricular pressure during ischemia, dronedarone reduced infarct size from 34 +/- 3% to 22 +/- 4% (p < 0.05) of the area at risk. Subendocardial blood flow during ischemia was not different between groups. The relationship between ischemic subendocardial blood flow in the area at risk and infarct size was displaced downwards, reflecting a direct cardioprotective action of dronedarone. CONCLUSION: The beneficial effect of dronedarone is attributed to cardioprotective properties, possibly through attenuation of calcium overload during myocardial ischemia/reperfusion.|Amiodarone/*analogs & derivatives/pharmacology[MESH]|Animals[MESH]|Anti-Arrhythmia Agents/pharmacology[MESH]|Blood Pressure/drug effects[MESH]|Calcium/metabolism[MESH]|Cardiotonic Agents/*pharmacology[MESH]|Coronary Circulation/drug effects[MESH]|Dronedarone[MESH]|Heart Rate/drug effects[MESH]|Myocardial Infarction/*drug therapy/physiopathology[MESH]|Myocardial Reperfusion Injury/*drug therapy/physiopathology[MESH]|Swine[MESH]|Swine, Miniature[MESH] |
