Dronedarone Versus Amiodarone in Preventing Premature Ventricular Contractions in an In Vitro Model of "Border Zone"

作者：Alexandre Joachim^*; Rouet Rene; Puddu Paolo Emilio; Beygui Farzin; Manrique Alain; Milliez Paul

来源：Journal of Cardiovascular Pharmacology, 2014, 63(1): 49-57.

DOI：10.1097/fjc.0000000000000023

• antiarrhythmic drugs
• ischemia
• reperfusion
• ventricular myocardium

Objective: To compare the acute ability of amiodarone and dronedarone (a noniodinated benzofuran derivative with a pharmacologic profile similar to amiodarone) to prevent premature ventricular contractions (PVCs) occurrence.
Methods: We used an in vitro model of rabbit right ventricle mimicking the "border zone" existing between normal and ischemic/reperfused regions to test acute electrophysiological effects of dronedarone and amiodarone both at 1 and 10 mu mol/L.
Results: Similar to amiodarone, dronedarone affected action potential parameters with multichannel blocking properties. Dronedarone at both concentrations was equivalent to amiodarone regarding PVCs occurrence, except regarding extrasystoles occurrence during the reperfusion period (dronedarone, 10 mu mol/L, was superior to amiodarone with extrasystoles incidence at 33% and 50%, respectively vs. 92% in controls, P < 0.05). Both dronedarone and amiodarone systematically induced conduction blocks during simulated ischemia (in 100% of preparations vs. 42% in controls, P < 0.05) and a marked decrease of V-max (to 24 and 23 V/s at 10 minutes of ischemia with 1 and 10 mu mol/L dronedarone versus 65 V/s in controls, P < 0.05), thus indicating class 1 antiarrhythmic effects. Both dronedarone and amiodarone at 10 mu mol/L induced an increase of APD(90) dispersion between normal and ischemic regions, without pro-arrhythmic effects.
Conclusions: Dronedarone and amiodarone have very similar electrophysiological effects in this in vitro model of border zone and were both efficient in preventing PVCs occurrence particularly through a class 1 antiarrhythmic effect.

• 出版日期2014-1