@article {2120, title = {Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart.}, journal = {J Am Coll Cardiol}, volume = {29}, year = {1997}, month = {03/1997}, pages = {831-42}, abstract = {

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\ videoimaging\ of electrical waves on the\ epicardial\ and endocardial\ surface\ of the Langendorff-perfused\ rabbitheart. 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.

}, keywords = {Action Potentials, Animals, Anti-Arrhythmia Agents, Arrhythmias, Cardiac, Electrocardiography, Heart, Heart Conduction System, Image Processing, Computer-Assisted, Models, Cardiovascular, Organ Culture Techniques, Perfusion, Piperidines, Pyridines, Quinidine, Rabbits, Torsades de Pointes}, issn = {0735-1097}, doi = {10.1016/S0735-1097(96)00588-8}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9091531}, author = {Asano, Y and Davidenko, J M and Baxter, Bill and Gray, R A and Jalife, J} } @article {2126, title = {Spiral waves of excitation underlie reentrant activity in isolated cardiac muscle.}, journal = {Circ Res}, volume = {72}, year = {1993}, month = {03/1993 }, pages = {631-50}, abstract = {

The mechanism of reentrant ventricular tachycardia was studied in computer simulations and in thin (approximately 20 x 20 x 0.5-mm) slices of dog and sheep ventricular epicardial muscle. A two-dimensional matrix consisting of 96 x 96 electrically coupled cells modeled by the FitzHugh-Nagumo equations was used to analyze the dynamics of self-sustaining reentrant activity in the form of elliptical spiral waves induced by premature stimulation. In homogeneous anisotropic media, spirals are stationary and may last indefinitely. However, the presence of small parameter gradients may lead to drifting and eventual termination of the spiral at the boundary of the medium. On the other hand, spirals may anchor and rotate around small discontinuities within the matrix. Similar results were obtained experimentally in 10 preparations whose electrical activity was monitored by means of a potentiometric dye and high-resolution optical mapping techniques; premature stimulation triggered reproducible episodes of sustained or nonsustained reentrant tachycardia in the form of spiral waves. As a rule, the spirals were elongated, with the major hemiaxis parallel to the longitudinal axis of the cells. The period of rotation (183 +/- 68 msec [mean +/- SD]) was longer than the refractory period (131 +/- 38 msec) and appeared to be determined by the size of the spiral{\textquoteright}s core, which was measured using a newly devised "frame-stack" plot. Drifting of spiral waves was also observed experimentally. Drift velocity was 9.8\% of the velocity of wave propagation. In some cases, the core became stationary by anchoring to small arteries or other heterogeneities, and the spiral rotated rhythmically for prolonged periods of time. Yet, when drift occurred, spatiotemporal variations in the excitation period were manifested as a result of a Doppler effect, with the excitation period ahead of the core being 20 +/- 6\% shorter than the excitation period behind the core. As a result of these coexisting frequencies, a pseudoelectrocardiogram of the activity in the presence of a drifting spiral wave exhibited "QRS complexes" with an undulating axis, which resembled those observed in patients with torsade de pointes. The overall results show that spiral wave activity is a property of cardiac muscle and suggest that such activity may be the common mechanism of a number of monomorphic and polymorphic tachycardias.

}, keywords = {Animals, Computer Simulation, Disease Models, Animal, Dogs, Electrophysiology, Sheep, Tachycardia, Atrioventricular Nodal Reentry, Torsades de Pointes}, issn = {0009-7330}, doi = {10.1161/01.RES.72.3.631}, url = {http://www.ncbi.nlm.nih.gov/pubmed/8431989}, author = {Pertsov, A V and Davidenko, J M and Salomonsz, R and Baxter, Bill and Jalife, J} }