@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 {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 {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 {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} } @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} }