Comparative study on the proarrhythmic effects of some antiarrhythmic agents

Area of Science:

• Cardiovascular Pharmacology
• Cardiac Electrophysiology
• Drug Safety Assessment

Background:

• Antiarrhythmic drugs can paradoxically promote arrhythmias (proarrhythmic activity).
• A lack of standardized in vitro models hindered the assessment of proarrhythmic drug effects.
• Sparse data existed for quantitative comparison of proarrhythmic drug activities.

Purpose of the Study:

• To quantitatively analyze and compare the arrhythmogenic risk of common antiarrhythmic drugs.
• To establish an in vitro model for assessing drug-induced proarrhythmia.
• To investigate the potential of propranolol in mitigating proarrhythmic effects.

Main Methods:

• Isolated perfused rabbit hearts were treated with varying concentrations of antiarrhythmic drugs.
• Epicardial mapping (256 unipolar leads) analyzed activation times, breakthrough points (BTP), and activation vectors (VEC).
• Beat similarity, activation-recovery interval (ARI), and ARI dispersion were evaluated.

Main Results:

• All tested antiarrhythmic agents disturbed the epicardial activation process, with flecainide and propafenone showing significant effects.
• Propafenone, quinidine, and disopyramide prolonged the activation-recovery interval (ARI); flecainide greatly enhanced ARI dispersion.
• Propranolol demonstrated a potential to reduce flecainide's proarrhythmic action by decreasing ARI dispersion.

Conclusions:

• A rank order of arrhythmogenic risk was established: flecainide > propafenone > quinidine > ajmaline > disopyramide > procainamide > mexiletine, lidocaine > sotalol.
• Propranolol may be beneficial in reducing the proarrhythmic risk associated with flecainide.
• The developed model provides a quantitative method for comparing drug-induced proarrhythmia.