OPTICAL MAPPING OF DRUG-INDUCED POLYMORPHIC ARRHYTHMIAS AND TORSADE-DE-POINTES IN THE ISOLATED RABBIT HEART

Objectives. This study sought to 1) test the hypothesis that in the se tting of bradycardia and drug-induced action potential prolongation, m ultiple foci of early afterdepolarizations (EADs) result in beat to be at changes in the origin and direction of the excitation wave front an d are responsible for polymorphic arrhythmias; and 2) determine whethe r EADs may initiate nonstationary reentry, giving rise to the typical torsade de pointes (TDP) pattern. Background. In the past, it has been difficult to associate EADs or reentry with the undulating electrocar diographic (EGG) pat terns of TDP. Methods. A voltage-sensitive dye wa s used for high resolution video imaging of electrical waves on the ep icardial and endocardial surface of the Langendorff-perfused rabbit he art. ECG and monophasic action potentials from the right septal region were also recorded. Bradycardia was induced by ablation of the atriov entricular node. Results. Perfusion of low potassium chloride Tyrode s olution plus quinidine led to prolongation of the action potential and the QT interval, Eventually, EADs and triggered activity ensued, givi ng rise to intermittent episodes of polymorphic arrhythmia. In one exp eriment, triggered activity was followed by a long episode of vortex l ike reentry with an ECG pattern characteristic of TDP. However, in mos t experiments, focal activity of varying origins and propagation patte rns was observed. Triggered responses also showed varying degrees of l ocal block. Similar results were obtained with E-4031. Burst pacing bo th at control conditions and in the presence of quinidine consistently led to vortex-like reentry whose ECG pattern resembled TDP. However, the cycle length of the arrhythmia with quinidine was longer than that for control ([mean +/- SEM] 194 +/- 12 vs. 132 +/- 8 ms, p < 0.03). C onclusions. Drug induced polymorphic ventricular arrhythmias may resul t from beat to beat changes in wave propagation patterns initiated by EADs or EAD-induced nonstationary reentrant activity. In contrast, bur st pacing-induced polymorphic tachycardia in the presence or absence o f drugs is the result of nonstationary reentrant activity. (C) 1997 by the American College of Cardiology.