ELECTROPHYSIOLOGICAL EFFECTS OF FLECAINIDE ON ANISOTROPIC CONDUCTION AND REENTRY IN INFARCTED CANINE HEARTS

Background The class IC antiarrhythmic drug flecainide has been shown to be ineffective for the treatment of ventricular arrhythmias in some patients who have had a prior myocardial infarction and sometimes eve n provoke arrhythmias (proarrhythmic effect). Since some ventricular t achycardias may be caused by anisotropic reentry, we determined the ef fects of flecainide on this mechanism for reentry in infarcted canine hearts in order to determine possible causes for its clinical effects. Methods and Results The effects of flecainide were determined on vent ricular tachycardia induced by programmed electrical stimulation in do gs with healing myocardial infarction 4 days after coronary artery occ lusion. Activation in the reentrant circuits causing tachycardia was m apped with a 196-channel computerized mapping system. We found that fl ecainide converted inducible unsustained ventricular tachycardia to in ducible sustained ventricular tachycardia by modifying conduction in t he reentrant circuit. In general, by slowing conduction, the reentrant wave front did not block after flecainide, leading to perpetuation of reentrant excitation. When sustained ventricular tachycardia could be induced before the drug, flecainide prolonged the coupling interval o f premature impulses necessary to induce tachycardia by lengthening th e line of block and slowing conduction around it. Flecainide also slow ed the rate of the tachycardia but did not terminate it. The anisotrop ic reentrant circuits were modified so that the central common pathway of ''figure-of-eight'' circuits was narrowed and lengthened due to ex tension of the lines of block that bounded the pathways. Extension of the lines of block resulted from depression of conduction in the direc tion transverse to the long axis of the myocardial fiber bundles cause d by flecainide. Flecainide also slowed conduction in the longitudinal direction in part of the circuits. The depressant effects of flecaini de on both longitudinal and transverse anisotropic conduction were qua ntified by pacing from the center of the electrode array and it was fo und, contrary to predictions, that transverse conduction was depressed as much as longitudinal conduction. Conclusions Flecainide slows cond uction in both the longitudinal and transverse direction relative to t he orientation of the myocardial fibers. This enables sustained reentr y to occur more easily. Flecainide does not cause conduction block in crucial regions of reentrant circuits (central common pathway) and the refore does not prevent reentrant tachycardia in healing infarcts.