Electrophysiological effects of flecainide enantiomers in canine Purkinje fibres.

Since flecainide is a chiral class I antiarrhythmic agent, we examined the basic electrophysiological effects of its enantiomers (10-(6) - 3 x 10(-5) mol/l) in isolated canine Purkinje fibres using standard microelectrode techniques. Frequency-dependent block was studied by pacing at cycle lengths of 300 and 2000 ms. Both enantiomers produced a marked, concentration-dependent decrease in maximum upstroke velocity (Vmax), with greater depression occurring at a cycle length of 300 ms. The concentration causing a 50% decrease in Vmax (EC50) at this pacing rate were 5.0 +/- 0.6 x 10(-6) mol/l for (+)-flecainide and 6.2 +/- 0.8 x 10(-6) mol/l for (-)-flecainide, and were not significantly different. Both enantiomers also produced a concentration- and frequency-dependent decrease in action potential amplitude and an increase in conduction time with no significant differences between the enantiomers. However, at the highest concentration studied (3 x 10(-5) mol/l), none of the nine tissues exposed to (+)-flecainide could be paced at 300 ms cycle length while five of eight tissues exposed to (-)-flecainide could be paced, suggesting the possibility of a small difference between the effects of the enantiomers on membrane responsiveness. The effect of the enantiomers on action potential duration (APD) also depended on pacing rate. At the longer cycle length, ADP50 was shortened to a maximum of 61 +/- 7% and 67 +/- 7% from baseline by (+)- and (-)-flecainide, respectively, whereas APD95 was shortened by 30 +/- 6% and 32 +/- 3% from baseline by (+)- and (-)-flecainide, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)