Simulation study of the effects of flecainide on ventricular muscle cells

Flecainide is a synthetic drug that blocks Na channels and can be classified as a class IC antiarrhythmic agent. In spite of its potent activity, there exists a great concern for its possible proarrhythmic consequences. The main objective of the present work is to study the effects of this drug on ventricular muscle cells, searching for possible mechanisms of proarrhythmia of the drug, and using mathematical models and computer simulations. At increasing concentrations of flecainide and increasing frequencies of stimulation, the authors' results show decreases in the maximum rate of rise of phase 0 of the action potential (4P), also decreases in the propagation velocity of APs, and very slight increases in the AP duration (APD). The authors' results suggest that a possible mechanism responsible for the proarrhythmic effects of flecainide may be based on the combination of potent reductions of AP velocity and an almost absent effect on APD and effective refractory period. This combination may favor the establishment of reentry, specially at increasing frequencies of stimulation.