@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 {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 {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} } @article {2128, title = {Stationary and drifting spiral waves of excitation in isolated cardiac muscle.}, journal = {Nature}, volume = {355}, year = {1992}, month = {01/1992}, pages = {349-51}, abstract = {

Excitable media can support spiral waves rotating around an organizing centre. Spiral waves have been discovered in different types of autocatalytic chemical reactions and in biological systems. The so-called {\textquoteright}re-entrant excitation{\textquoteright} of myocardial cells, causing the most dangerous cardiac arrhythmias, including ventricular tachycardia and fibrillation, could be the result of spiral waves. Here we use a potentiometric dye in combination with CCD (charge-coupled device) imaging technology to demonstrate spiral waves in the heart muscle. The spirals were elongated and the rotation period, Ts, was about 180 ms (3-5 times faster than normal heart rate). In most episodes, the spiral was anchored to small arteries or bands of connective tissue, and gave rise to stationary rotations. In some cases, the core drifted away from its site of origin and dissipated at a tissue border. Drift was associated with a Doppler shift in the local excitation period, T, with T ahead of the core being about 20\% shorter than T behind the core.

}, keywords = {Animals, Dogs, Heart, Mathematics, Membrane Potentials, Models, Biological, Myocardial Contraction, Sheep}, issn = {0028-0836}, doi = {10.1038/355349a0}, url = {http://www.ncbi.nlm.nih.gov/pubmed/1731248}, author = {Davidenko, J M and Pertsov, A V and Salomonsz, R and Baxter, Bill and Jalife, J} }