Author + information
- Received July 10, 1996
- Revision received December 11, 1996
- Accepted December 11, 1996
- Published online March 15, 1997.
- Yukio Asano, MDA,
- Jorge M. Davidenko, MDA,
- William T. Baxter, MSA,
- Richard A. Gray, PhDA and
- José Jalife, MD, FACCA,* ()
- ↵*Dr. José Jalife, Department of Pharmacology, SUNY Health Science Center, 766 Irving Avenue, Syracuse, New York 13210.
Objectives. This study sought to 1) test the hypothesis that in the setting of bradycardia and drug-induced action potential prolongation, multiple foci of early afterdepolarizations (EADs) result in beat to beat changes in the origin and direction of the excitation wave front and are responsible for polymorphic arrhythmias; and 2) determine whether 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 electrocardiographic (ECG) patterns of TDP.
Methods. A voltage-sensitive dye was used for high resolution video imaging of electrical waves on the epicardial and endocardial surface of the Langendorff-perfused rabbit heart. ECG and monophasic action potentials from the right septal region were also recorded. Bradycardia was induced by ablation of the atrioventricular node.
Results. Perfusion of low potassium chloride Tyrode solution plus quinidine led to prolongation of the action potential and the QT interval. Eventually, EADs and triggered activity ensued, giving rise to intermittent episodes of polymorphic arrhythmia. In one experiment, triggered activity was followed by a long episode of vortex-like reentry with an ECG pattern characteristic of TDP. However, in most experiments, focal activity of varying origins and propagation patterns was observed. Triggered responses also showed varying degrees of local block. Similar results were obtained with E-4031. Burst pacing both 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).
Conclusions. Drug-induced polymorphic ventricular arrhythmias may result from beat to beat changes in wave propagation patterns initiated by EADs or EAD-induced nonstationary reentrant activity. In contrast, burst pacing–induced polymorphic tachycardia in the presence or absence of drugs is the result of nonstationary reentrant activity.
(J Am Coll Cardiol 1997;29:831–42)
☆ This study was supported in part by Grant P01-HL39707 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Dr. Asano is a Fellow of the American Heart Association, New York State Affiliate. Dr. Davidenko is an Established Investigator of the American Heart Association, Dallas, Texas.
- Received July 10, 1996.
- Revision received December 11, 1996.
- Accepted December 11, 1996.
- The American College of Cardiology