@article {2117, title = {Visualizing excitation waves inside cardiac muscle using transillumination.}, journal = {Biophys J}, volume = {80}, year = {2001}, month = {01/2001}, pages = {516-30}, abstract = {

Voltage-sensitive fluorescent dyes have become powerful tools for the visualization of excitation propagation in the\ heart. However, until recently they were used exclusively for surface recordings. Here we demonstrate the possibility of visualizing the electrical activity from inside cardiac muscle via fluorescence measurements in the transillumination mode (in which the light source and photodetector are on opposite sides of the preparation). This mode enables the detection of light escaping from layers deep within the tissue. Experiments were conducted in perfused (8 mm thick) slabs of sheep right ventricular wall stained with the voltage-sensitive dye di-4-ANEPPS. Although the amplitude and signal-to-noise ratio recorded in the transillumination mode were significantly smaller than those recorded in the epi-illumination mode, they were sufficient to reliably determine the activation sequence. Penetration depths (spatial decay constants) derived from measurements of light attenuation in cardiac muscle were 0.8 mm for excitation (520 +/- 30 nm) and 1.3 mm for emission wavelengths (640 +/- 50 nm). Estimates of emitted fluorescence based on these attenuation values in 8-mm-thick tissue suggest that 90\% of the transillumination signal originates from a 4-mm-thick layer near the illuminated surface. A 69\% fraction of the recorded signal originates from \> or =1 mm below the surface. Transillumination recordings may be combined with endocardial and epicardial surface recordings to obtain information about three-dimensional propagation in the thickness of the myocardial wall. We show an example in which transillumination reveals an intramural reentry, undetectable in surface recordings.

}, keywords = {Animals, Biophysical Phenomena, Biophysics, Electrophysiology, Endocardium, Fluorescent Dyes, Heart, Models, Cardiovascular, Myocardium, Optics and Photonics, Perfusion, Pericardium, Pyridinium Compounds, Sheep}, issn = {0006-3495}, doi = {10.1016/S0006-3495(01)76034-1}, url = {http://www.ncbi.nlm.nih.gov/pubmed/11159422}, author = {Baxter, Bill and Mironov, S F and Zaitsev, A V and Jalife, J and Pertsov, A V} } @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 {2118, title = {Technical features of a CCD video camera system to record cardiac fluorescence data.}, journal = {Ann Biomed Eng}, volume = {25}, year = {1997}, month = {07/1997}, pages = {713-25}, abstract = {

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.

}, keywords = {Action Potentials, Algorithms, Animals, Body Surface Potential Mapping, Calibration, Computer Simulation, Electric Conductivity, Fluorescent Dyes, Image Processing, Computer-Assisted, Models, Cardiovascular, Sheep, Ventricular Function, Video Recording}, issn = {0090-6964}, doi = {10.1007/BF02684848}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9236983}, author = {Baxter, Bill and Davidenko, J M and Loew, L M and Wuskell, J P and Jalife, J} } @article {2121, title = {Vortex shedding as a precursor of turbulent electrical activity in cardiac muscle.}, journal = {Biophys J}, volume = {70}, year = {1996}, month = {03/1996}, pages = {1105-11}, abstract = {

In cardiac tissue, during partial blockade of the membrane sodium channels, or at high frequencies of excitation, inexcitable obstacles with sharp edges may destabilize the propagation of electrical excitation waves, causing the formation of self-sustained vortices and turbulent cardiac electrical activity. The formation of such vortices, which visually resembles vortex shedding in hydrodynamic turbulent flows, was observed in sheep epicardial tissue using voltage-sensitive dyes in combination with video-imaging techniques. Vortex shedding is a potential mechanism leading to the spontaneous initiation of uncontrolled high-frequency excitation of the heart.

}, keywords = {Animals, Biophysical Phenomena, Biophysics, Cell Membrane, Computer Simulation, Electric Stimulation, Electrochemistry, Electrophysiology, Heart, Models, Cardiovascular, Myocardial Contraction, Myocardium, Sheep, Sodium Channels}, issn = {0006-3495}, doi = {10.1016/S0006-3495(96)79691-1}, url = {http://www.ncbi.nlm.nih.gov/pubmed/8785270}, author = {Cabo, C and Pertsov, A V and Davidenko, J M and Baxter, Bill and Gray, R A and Jalife, J} } @article {2122, title = {Effects of pacing on stationary reentrant activity. Theoretical and experimental study.}, journal = {Circ Res}, volume = {77}, year = {1995}, month = {12/1995}, pages = {1166-79}, abstract = {

It is well known that electrical pacing may either terminate or change the rate and/or ECG appearance of reentrant ventricular tachycardia. However, the dynamics of interaction of reentrant waves with waves initiated by external pacing are poorly understood. Prevailing concepts are based on simplistic models in which propagation occurs in one-dimensional rings of cardiac tissue. Since reentrant activation in the ventricles occurs in two or three dimensions, such concepts might be insufficient to explain the mechanisms of pacing-induced effects. We used numerical and biological models of cardiac excitation to explore the phenomena, which may take place as a result of electrical pacing during functionally determined reentry. Computer simulations of a two-dimensional array of electrically coupled FitzHugh-Nagumo cells were used to predict the response patterns expected from thin slices of sheep ventricular epicardial muscle, in which self-sustaining reentrant activity in the form of spiral waves was consistently initiated by premature stimulation and monitored by means of video mapping techniques. The results show that depending on their timing and shape, externally induced waves may collide with the self-sustaining spiral and result in one of three possible outcomes: (1) direct annihilation of the spiral, (2) multiplication of the spiral, or (3) shift of the spiral center (ie, core). Multiplication and shift of the spiral core were attended by changes in rate and morphology of the arrhythmia as seen by "pseudo-ECGs." Furthermore, delayed termination (ie, termination of the activity one to three cycles after the stimulus) occurred after both multiplication and shift of the spiral center. Both numerical predictions and experimental results support the hypothesis that whether a pacing stimulus will terminate a reentrant arrhythmia or modify its ECG appearance depends on whether the interactions between the externally induced wave and the spiral wave result in the de novo formation of one or more "wavebreaks." The final outcome depends on the stimulus parameters (ie, position and size of the electrodes and timing of the stimulus) as well as on the position of the newly formed wavebreak(s) in relation to that of the original wave.

}, keywords = {Acceleration, Animals, Cardiac Pacing, Artificial, Computer Simulation, Deceleration, Electrocardiography, Models, Cardiovascular, Sheep, Tachycardia, Ventricular}, issn = {0009-7330}, doi = {10.1161/01.RES.77.6.1166}, url = {http://www.ncbi.nlm.nih.gov/pubmed/7586230}, author = {Davidenko, J M and Salomonsz, R and Pertsov, A V and Baxter, Bill and Jalife, J} } @article {2123, title = {Mechanisms of cardiac fibrillation.}, journal = {Science}, volume = {270}, year = {1995}, month = {11/1995}, pages = {1222-3; author reply 1224-5}, keywords = {Animals, Computer Simulation, Electrocardiography, Heart Ventricles, Models, Cardiovascular, Rabbits, Ventricular Fibrillation}, issn = {0036-8075}, doi = {10.1126/science.270.5239.1222}, url = {http://www.ncbi.nlm.nih.gov/pubmed/7502055}, author = {Gray, R A and Jalife, J and Panfilov, A and Baxter, Bill and Cabo, C and Davidenko, J M and Pertsov, A V} } @article {2124, title = {Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart.}, journal = {Circulation}, volume = {91}, year = {1995}, month = {05/1995 }, pages = {2454-69}, abstract = {

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.

}, keywords = {Animals, Electrocardiography, Heart, Image Processing, Computer-Assisted, Models, Cardiovascular, Perfusion, Rabbits, Tachycardia, Ventricular}, issn = {0009-7322}, doi = {10.1161/01.CIR.91.9.2454}, url = {http://www.ncbi.nlm.nih.gov/pubmed/7729033}, author = {Gray, R A and Jalife, J and Panfilov, A and Baxter, Bill and Cabo, C and Davidenko, J M and Pertsov, A V} } @article {2125, title = {Wave-front curvature as a cause of slow conduction and block in isolated cardiac muscle.}, journal = {Circ Res}, volume = {75}, year = {1994}, month = {12/1994}, pages = {1014-28}, abstract = {

We have investigated the role of wave-front curvature on propagation by following the wave front that was diffracted through a narrow isthmus created in a two-dimensional ionic model (Luo-Rudy) of ventricular muscle and in a thin (0.5-mm) sheet of sheep ventricular epicardial muscle. The electrical activity in the experimental preparations was imaged by using a high-resolution video camera that monitored the changes in fluorescence of the potentiometric dye di-4-ANEPPS on the surface of the tissue. Isthmuses were created both parallel and perpendicular to the fiber orientation. In both numerical and biological experiments, when a planar wave front reached the isthmus, it was diffracted to an elliptical wave front whose pronounced curvature was very similar to that of a wave front initiated by point stimulation. In addition, the velocity of propagation was reduced in relation to that of the original planar wave. Furthermore, as shown by the numerical results, wave-front curvature changed as a function of the distance from the isthmus. Such changes in local curvature were accompanied by corresponding changes in velocity of propagation. In the model, the critical isthmus width was 200 microns for longitudinal propagation and 600 microns for transverse propagation of a single planar wave initiated proximal to the isthmus. In the experiments, propagation depended on the width of the isthmus for a fixed stimulation frequency. Propagation through an isthmus of fixed width was rate dependent both along and across fibers. Thus, the critical isthmus width for propagation was estimated in both directions for different frequencies of stimulation. In the longitudinal direction, for cycle lengths between 200 and 500 milliseconds, the critical width was \< 1 mm; for 150 milliseconds, it was estimated to be between 1.3 and 2 mm; and for the maximum frequency of stimulation (117 +/- 15 milliseconds), it was \> 2.5 mm. In the transverse direction, critical width was between 1.78 and 2.32 mm for a basic cycle length of 200 milliseconds. It increased to values between 2.46 and 3.53 mm for a basic cycle length of 150 milliseconds. The overall results demonstrate that the curvature of the wave front plays an important role in propagation in two-dimensional cardiac muscle and that changes in curvature may cause slow conduction or block.

}, keywords = {Animals, Computer Simulation, Electric Conductivity, Heart, Heart Block, Heart Conduction System, Humans, Models, Cardiovascular, Motion Pictures as Topic, Sheep, Staining and Labeling}, issn = {0009-7330}, url = {http://www.ncbi.nlm.nih.gov/pubmed/7525101}, author = {Cabo, C and Pertsov, A V and Baxter, Bill and Davidenko, J M and Gray, R A and Jalife, J} }