TY - JOUR T1 - Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart. JF - J Am Coll Cardiol Y1 - 1997 A1 - Asano, Y A1 - Davidenko, J M A1 - Baxter, Bill A1 - Gray, R A A1 - Jalife, J KW - Action Potentials KW - Animals KW - Anti-Arrhythmia Agents KW - Arrhythmias, Cardiac KW - Electrocardiography KW - Heart KW - Heart Conduction System KW - Image Processing, Computer-Assisted KW - Models, Cardiovascular KW - Organ Culture Techniques KW - Perfusion KW - Piperidines KW - Pyridines KW - Quinidine KW - Rabbits KW - Torsades de Pointes AB -

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.

VL - 29 UR - http://www.ncbi.nlm.nih.gov/pubmed/9091531 IS - 4 ER - TY - JOUR T1 - Technical features of a CCD video camera system to record cardiac fluorescence data. JF - Ann Biomed Eng Y1 - 1997 A1 - Baxter, Bill A1 - Davidenko, J M A1 - Loew, L M A1 - Wuskell, J P A1 - Jalife, J KW - Action Potentials KW - Algorithms KW - Animals KW - Body Surface Potential Mapping KW - Calibration KW - Computer Simulation KW - Electric Conductivity KW - Fluorescent Dyes KW - Image Processing, Computer-Assisted KW - Models, Cardiovascular KW - Sheep KW - Ventricular Function KW - Video Recording AB -

A charge-coupled device (CCD) camera was used to acquire movies of transmembrane activity from thin slices of sheep ventricular epicardial muscle stained with a voltage-sensitive dye. Compared with photodiodes, CCDs have high spatial resolution, but low temporal resolution. Spatial resolution in our system ranged from 0.04 to 0.14 mm/pixel; the acquisition rate was 60, 120, or 240 frames/sec. Propagating waves were readily visualized after subtraction of a background image. The optical signal had an amplitude of 1 to 6 gray levels, with signal-to-noise ratios between 1.5 and 4.4. Because CCD cameras integrate light over the frame interval, moving objects, including propagating waves, are blurred in the resulting movies. A computer model of such an integrating imaging system was developed to study the effects of blur, noise, filtering, and quantization on the ability to measure conduction velocity and action potential duration (APD). The model indicated that blurring, filtering, and quantization do not affect the ability to localize wave fronts in the optical data (i.e., no systematic error in determining spatial position), but noise does increase the uncertainty of the measurements. The model also showed that the low frame rates of the CCD camera introduced a systematic error in the calculation of APD: for cutoff levels > 50%, the APD was erroneously long. Both noise and quantization increased the uncertainty in the APD measurements. The optical measures of conduction velocity were not significantly different from those measured simultaneously with microelectrodes. Optical APDs, however, were longer than the electrically recorded APDs. This APD error could be reduced by using the 50% cutoff level and the fastest frame rate possible.

VL - 25 UR - http://www.ncbi.nlm.nih.gov/pubmed/9236983 IS - 4 ER -