Factors affecting epicardial dispersion of repolarization: a mapping studyin the isolated porcine heart

Objective: Non-uniform drug-induced prolongation of repolarization predomin ating in the midmyocardial (M) cell layers has been shown to be responsible for perpetuation of reentry, giving rise to torsade de pointes. However, t he absence of M cells in immature animals, especially the pig, suggests oth er possible underlying mechanisms. We sought to examine, in this species, t he effects of predisposing factors to torsade de pointes on the dispersion of epicardial repolarization and their contribution to arrhythmogenesis. Me thods: Computerized mapping of repolarization and activation was conducted on the epicardial surface in 29 Langendorff-perfused hearts of eight-week-o ld pigs. Activation-recovery intervals were measured simultaneously from 12 8 unipolar electrograms. Results: Baseline iso-interval maps were dipolar ( 41%) or multipolar (59%). Dispersion of repolarization was reverse frequenc y-dependent but was unaffected by lowering [K+](o). DL-Sotalol (0.1 mmol/l) reinforced local gradients and thus increased epicardial dispersion, where as intramural recordings did not demonstrate any predominant effect in midm yocardial layers. Phenylephrine (1 mu mol/l) notably augmented DL-sotalol e ffects. After [Mg++](o) lowering, although dispersion was not significantly increased, or-sotalol was associated with the spontaneous occurrence of po lymorphic ventricular tachycardia in seven out of nine experiments. When ma ps of repolarization of escape beats were compared with activation maps of first arrhythmic beats, an are of functional dissociation was observed in t he vicinity of a steep gradient of repolarization in two out of nine tachyc ardias. Conclusion: Epicardial dispersion of repolarization is increased by slow rates, DL-sotalol and phenylephrine but is not the only requirement f or initiation of polymorphic ventricular tachycardia. In combination with o ther factors, it helps continuation of the arrhythmia in this model. (C) 19 99 Elsevier Science B.V. All rights reserved.