TY - JOUR T1 - Quantification of effects of global ischemia on dynamics of ventricular fibrillation in isolated rabbit heart. JF - Circulation Y1 - 1998 A1 - Mandapati, R A1 - Asano, Y A1 - Baxter, Bill A1 - Gray, R A A1 - Davidenko, J M A1 - Jalife, J KW - Animals KW - Electrocardiography KW - Linear Models KW - Myocardial Ischemia KW - Rabbits KW - Rotation KW - Sodium Channel Blockers KW - Tetrodotoxin KW - Ventricular Fibrillation KW - Video Recording AB -

BACKGROUND: 

Ventricular fibrillation (VF) leads to global ischemia of the heart. After 1 to 2 minutes of onset, the VF rate decreases and appears more organized. The objectives of this study were to determine the effects of no-flow global ischemia on nonlinear wave dynamics and establish the mechanism of ischemia-induced slowing of the VF rate.

METHODS AND RESULTS: 

Activation patterns of VF in the Langendorff-perfused rabbit heart were studied with the use of 2 protocols: (1) 15 minutes of no-flow global ischemia followed by reperfusion (n=7) and (2) decreased excitability induced by perfusion with 5 micromol/L of tetrodotoxin (TTX) followed by washout (n=3). Video imaging ( approximately 7500 pixels per frame; 240 frames per second) with a voltage-sensitive dye, ECG, and signal processing (fast Fourier transform) were used for analysis. The dominant frequency of VF decreased from 13.5+/-1.3 during control to 9.3+/-1.4 Hz at 5 minutes of global ischemia (P<0.02). The dominant frequency decreased from 13.9+/-1.1 during control to 7.0+/-0.3 Hz at 2 minutes of TTX infusion (P<0.001). The rotation period of rotors on the epicardial surface (n=27) strongly correlated with the inverse dominant frequency of the corresponding episode of VF (R2=0. 93). The core area, measured for 27 transiently appearing rotors, was 5.3+/-0.7 mm2 during control. A remarkable increase in core area was observed both during global ischemia (13.6+/-1.7 mm2; P<0.001) and TTX perfusion (16.8+/-3.6 mm2; P<0.001). Density of wave fronts decreased during both global ischemia (P<0.002) and TTX perfusion (P<0.002) compared with control.

CONCLUSIONS: 

This study suggests that rotating spiral waves are most likely the underlying mechanism of VF and contribute to its frequency content. Ischemia-induced decrease in the VF rate results from an increase in the rotation period of spiral waves that occurs secondary to an increase in their core area. Remarkably, similar findings in the TTX protocol suggest that reduced excitability during ischemia is an important underlying mechanism for the changes seen.

VL - 98 UR - http://www.ncbi.nlm.nih.gov/pubmed/9778336 IS - 16 ER - 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 - Mechanisms of cardiac fibrillation. JF - Science Y1 - 1995 A1 - Gray, R A A1 - Jalife, J A1 - Panfilov, A A1 - Baxter, Bill A1 - Cabo, C A1 - Davidenko, J M A1 - Pertsov, A V KW - Animals KW - Computer Simulation KW - Electrocardiography KW - Heart Ventricles KW - Models, Cardiovascular KW - Rabbits KW - Ventricular Fibrillation VL - 270 UR - http://www.ncbi.nlm.nih.gov/pubmed/7502055 IS - 5239 ER - TY - JOUR T1 - Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart. JF - Circulation Y1 - 1995 A1 - Gray, R A A1 - Jalife, J A1 - Panfilov, A A1 - Baxter, Bill A1 - Cabo, C A1 - Davidenko, J M A1 - Pertsov, A V KW - Animals KW - Electrocardiography KW - Heart KW - Image Processing, Computer-Assisted KW - Models, Cardiovascular KW - Perfusion KW - Rabbits KW - Tachycardia, Ventricular AB -

BACKGROUND: 

Ventricular tachycardia may result from vortexlike reentrant excitation of the myocardium. Our general hypothesis is that in the structurally normal heart, these arrhythmias are the result of one or two nonstationary three-dimensional electrical scroll waves activating the heart muscle at very high frequencies.

METHODS AND RESULTS: 

We used a combination of high-resolution video imaging, electrocardiography, and image processing in the isolated rabbit heart, together with mathematical modeling. We characterized the dynamics of changes in transmembrane potential patterns on the epicardial surface of the ventricles using optical mapping. Image processing techniques were used to identify the surface manifestation of the reentrant organizing centers, and the location of these centers was used to determine the movement of the reentrant pathway. We also used numerical simulations incorporating Fitzhugh-Nagumo kinetics and realistic heart geometry to study how stationary and nonstationary scroll waves are manifest on the epicardial surface and in the simulated ECG. We present epicardial surface manifestations (reentrant spiral waves) and ECG patterns of nonstationary reentrant activity that are consistent with those generated by scroll waves established at the right and left ventricles. We identified the organizing centers of the reentrant circuits on the epicardial surface during polymorphic tachycardia, and these centers moved during the episodes. In addition, the arrhythmias that showed the greatest movement of the reentrant centers displayed the largest changes in QRS morphology. The numerical simulations showed that stationary scroll waves give rise to monomorphic ECG signals, but nonstationary meandering scroll waves give rise to undulating ECGs characteristic of torsade de pointes.

CONCLUSIONS: 

Polymorphic ventricular tachycardia in the healthy, isolated rabbit heart is the result of either a single or paired ("figure-of-eight") nonstationary scroll waves. The extent of the scroll wave movement corresponds to the degree of polymorphism in the ECG. These results are consistent with our numerical simulations that showed monomorphic ECG patterns of activity for stationary scroll waves but polymorphic patterns for scroll waves that were nonstationary.

VL - 91 UR - http://www.ncbi.nlm.nih.gov/pubmed/7729033 IS - 9 ER -