Mechanisms of Chemical Atrial Defibrillation by Flecainide and Ibutilide.

BACKGROUND: Effective and safe pharmacological approaches for atrial defibrillation offer several potential advantages over techniques like ablation. Pharmacological therapy is noninvasive, involving no risk associated with the procedure or resulting complications. Moreover, acute drug intervention with existing drugs is likely to be low cost and broadly accessible, thereby addressing a central tenet of health equity. OBJECTIVES: This study aims to investigate ibutilide-mediated action potential prolongation to promote use-dependent effects of flecainide on Na(+) channels by reducing the diastolic interval and, consequently, drug unbinding to reduce action potential excitability in atrial tissue and terminate re-entrant arrhythmia. METHODS: The authors utilize a modeling and simulation approach to predict the specific combinations of sodium- and potassium-channel blocking drugs to chemically terminate atrial re-entry. RESULTS: Computational modeling and simulation show that acute application of flecainide and ibutilide is a promising example of drug repurposing that may constitute a promising combination for chemical atrial defibrillation. CONCLUSIONS: We predict the drug concentrations that promote efficacy of flecainide and ibutilide used in combination for atrial chemical defibrillation. We also predict the potential safety pharmacology impact of this drug combination on ventricular electrophysiology.