Cellular electrophysiological effects of flecainide on human atrial fibres

Abstract

The aim of the study was to examine the electrophysiological characteristics of human atrial specimens collected during heart surgery and to investigate the effects of the class I antiarrhythmic agent flecainide on their electrical activity. Atrial specimens were studied using standard microelectrode techniques, with and without superfused flecainide (5 x 10(-7) M) or the transient outward current inhibitor 4-aminopyridine (0.5 mM). Atrial fragments 0.5-1.0 cm2 were obtained at operation from 34 patients, mean age 30 years. There was no history of previous atrial arrhythmia in any patient and drug therapy was stopped 24 h before surgery. Two types of transmembrane action potential were identified: (1) triangular shaped potentials (group A, classically found in animal models); (2) potentials with a large plateau preceded by a notch (group B). The effect of flecainide was compared on the the two types of action potential. In both, flecainide lessened the depolarisation rate. In group B, but not in group A, it increased the action potential duration at 50% and 90% repolarisation (APD50, APD90) and the effective refractory period. The notch in group B action potentials is generated by transient outward currents (Ito). Inhibition of these currents, either by increasing the pacing rate or by adding 4-aminopyridine, limited the increase in APD50, APD90, and effective refractory period generated by the presence of flecainide. The effects of flecainide on the atrial repolarisation process depend on the shape of the action potential. These effects are more marked in cells with a plateau, where Ito is activated.