Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart
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Updated: Oct 13, 2026
Multiparametric Optical Mapping of the Langendorff-perfused Rabbit Heart
Published on: September 13, 2011
Y Asano1, J M Davidenko, W T Baxter
1Department of Pharmacology, State University of New York Health Science Center, Syracuse 13210, USA.
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.
Insights
Early afterdepolarizations (EADs) can cause polymorphic arrhythmias by altering wave propagation. Nonstationary reentry, initiated by EADs or burst pacing, underlies torsade de pointes (TDP) and other polymorphic tachycardias.
Area of Science:
- Cardiac Electrophysiology
- Arrhythmogenesis
- Computational Biology
Background:
- The electrocardiographic (ECG) patterns of torsade de pointes (TDP) have historically been difficult to link directly to early afterdepolarizations (EADs) or reentry mechanisms.
- Understanding the precise mechanisms initiating polymorphic arrhythmias remains a challenge.
Purpose of the Study:
- To investigate if multiple foci of early afterdepolarizations (EADs) cause beat-to-beat variations in cardiac excitation wavefronts during bradycardia and drug-induced action potential prolongation, leading to polymorphic arrhythmias.
- To determine if EADs can initiate nonstationary reentry, generating the characteristic torsade de pointes (TDP) ECG pattern.
Main Methods:
- Utilized voltage-sensitive dye for high-resolution video imaging of electrical wave propagation on rabbit heart surfaces (epicardial and endocardial).
- Recorded electrocardiograms (ECG) and monophasic action potentials from the septal region.
- Induced bradycardia via atrioventricular node ablation.
Main Results:
- Drug administration (quinidine, E-4031) with low potassium Tyrode solution induced action potential prolongation, EADs, triggered activity, and intermittent polymorphic arrhythmias.
- Observed focal activity with varying origins and propagation patterns, and local block in triggered responses.
- Burst pacing induced vortex-like reentry resembling TDP, with longer cycle lengths in the presence of quinidine.
Conclusions:
- Drug-induced polymorphic ventricular arrhythmias may arise from EADs or EAD-induced nonstationary reentry, causing dynamic changes in wave propagation.
- Burst pacing-induced polymorphic tachycardia, with or without drugs, results from nonstationary reentrant activity.
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