EFFECTS OF THE ENANTIOMERS OF FLECAINIDE ON ACTION-POTENTIAL CHARACTERISTICS IN THE GUINEA-PIG PAPILLARY-MUSCLE

The enantiomers of flecainide, a Class Ic antiarrhythmic agent, were tested in the guinea-pig papillary muscle using the standard microelectrode technique. In 5.4 mM external K+ and at a stimulation frequency of 1 Hz, significant differences were observed in the effect of the enantiomers on maximal rate of depolarization, action potential amplitude and action potential duration. Maximal rate of depolarization and action potential amplitude were more suppressed in the presence of (+)flecainide. Maximal rate of depolarization was reduced to 54.4 +/- 1.4% (n = 23) (mean +/- S.E.M.) of maximum in the presence of 7.2-mu-M (+)flecainide and to 60.5 +/- 1.1% (n = 24) in the presence of the same concentration of (-)flecainide. The stimulation interval used had a pronounced influence on maximal rate of depolarization for both enantiomers. At almost all stimulation intervals tested, block was larger for (+)flecainide than for (-)flecainide. When the stimulation interval was shortened from 10 sec to 0.25 sec, the maximal rate of depolarization was reduced from 89.8 +/- 0.8% (n = 13) to 37.4 +/- 2.3% (n = 10) of the control in the presence of 7.2-mu-M of (+)flecainide and from 91.7 +/- 0.8% (n = 14) to 44.9 +/- 1.6% (n = 12) when the same concentration of (-)flecainide was used. The effect on maximal rate of depolarization was also voltage-dependent. For both enantiomers, inactivation curves, recorded at a frequency of 0.6/min, were shifted to more negative potentials. There was no significant difference in magnitude of shift between the two enantiomers.