TY - JOUR T1 - Visualizing excitation waves inside cardiac muscle using transillumination. JF - Biophys J Y1 - 2001 A1 - Baxter, Bill A1 - Mironov, S F A1 - Zaitsev, A V A1 - Jalife, J A1 - Pertsov, A V KW - Animals KW - Biophysical Phenomena KW - Biophysics KW - Electrophysiology KW - Endocardium KW - Fluorescent Dyes KW - Heart KW - Models, Cardiovascular KW - Myocardium KW - Optics and Photonics KW - Perfusion KW - Pericardium KW - Pyridinium Compounds KW - Sheep AB -

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.

VL - 80 UR - http://www.ncbi.nlm.nih.gov/pubmed/11159422 IS - 1 ER - TY - JOUR T1 - Video imaging of re-entry on the epicardial surface of the isolated rabbit heart. JF - Computational Biology of the Heart Y1 - 1997 A1 - Baxter, Bill A1 - Gray, R A A1 - Cabo, C A1 - Davidenko, J M A1 - Pertsov, A V A1 - Jalife, J UR - http://www.researchgate.net/publication/266334442_Video_imaging_of_re-entry_on_the_epicardial_surface_of_the_isolated_rabbit_heart ER - TY - JOUR T1 - Vortex shedding as a precursor of turbulent electrical activity in cardiac muscle. JF - Biophys J Y1 - 1996 A1 - Cabo, C A1 - Pertsov, A V A1 - Davidenko, J M A1 - Baxter, Bill A1 - Gray, R A A1 - Jalife, J KW - Animals KW - Biophysical Phenomena KW - Biophysics KW - Cell Membrane KW - Computer Simulation KW - Electric Stimulation KW - Electrochemistry KW - Electrophysiology KW - Heart KW - Models, Cardiovascular KW - Myocardial Contraction KW - Myocardium KW - Sheep KW - Sodium Channels AB -

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.

VL - 70 UR - http://www.ncbi.nlm.nih.gov/pubmed/8785270 IS - 3 ER - TY - JOUR T1 - Effects of pacing on stationary reentrant activity. Theoretical and experimental study. JF - Circ Res Y1 - 1995 A1 - Davidenko, J M A1 - Salomonsz, R A1 - Pertsov, A V A1 - Baxter, Bill A1 - Jalife, J KW - Acceleration KW - Animals KW - Cardiac Pacing, Artificial KW - Computer Simulation KW - Deceleration KW - Electrocardiography KW - Models, Cardiovascular KW - Sheep KW - Tachycardia, Ventricular AB -

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.

VL - 77 UR - http://www.ncbi.nlm.nih.gov/pubmed/7586230 IS - 6 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 - TY - JOUR T1 - Wave-front curvature as a cause of slow conduction and block in isolated cardiac muscle. JF - Circ Res Y1 - 1994 A1 - Cabo, C A1 - Pertsov, A V A1 - Baxter, Bill A1 - Davidenko, J M A1 - Gray, R A A1 - Jalife, J KW - Animals KW - Computer Simulation KW - Electric Conductivity KW - Heart KW - Heart Block KW - Heart Conduction System KW - Humans KW - Models, Cardiovascular KW - Motion Pictures as Topic KW - Sheep KW - Staining and Labeling AB -

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.

VL - 75 UR - http://www.ncbi.nlm.nih.gov/pubmed/7525101 IS - 6 ER - TY - JOUR T1 - Spiral waves of excitation underlie reentrant activity in isolated cardiac muscle. JF - Circ Res Y1 - 1993 A1 - Pertsov, A V A1 - Davidenko, J M A1 - Salomonsz, R A1 - Baxter, Bill A1 - Jalife, J KW - Animals KW - Computer Simulation KW - Disease Models, Animal KW - Dogs KW - Electrophysiology KW - Sheep KW - Tachycardia, Atrioventricular Nodal Reentry KW - Torsades de Pointes AB -

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'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.

VL - 72 UR - http://www.ncbi.nlm.nih.gov/pubmed/8431989 IS - 3 ER - TY - JOUR T1 - Spatiotemporal irregularities of spiral wave activity in isolated ventricular muscle. JF - J Electrocardiol Y1 - 1992 A1 - Davidenko, J M A1 - Pertsov, A V A1 - Salomonsz, R A1 - Baxter, Bill A1 - Jalife, J KW - Animals KW - Cardiac Pacing, Artificial KW - Fluorescent Dyes KW - Heart Conduction System KW - Membrane Potentials KW - Optics and Photonics KW - Pericardium KW - Signal Processing, Computer-Assisted KW - Tachycardia KW - Ventricular Function AB -

Voltage-sensitive dyes and high resolution optical mapping were used to analyze the characteristics of spiral waves of excitation in isolated ventricular myocardium. In addition, analytical techniques, which have been previously used in the study of the characteristics of spiral waves in chemical reactions, were applied to determine the voltage structure of the center of the rotating activity (ie, the core). During stable spiral wave activity local activation occurs in a periodic fashion (ie, 1:1 stimulus: response activation ratio) throughout the preparation, except at the core, which is a small elongated area where the activity is of low voltage and the activation ratio is 1:0. The voltage amplitude increases gradually from the center of the core to the periphery. In some cases, however, regular activation patterns at the periphery may coexist with irregular local activation patterns near the core. Such a spatiotemporal irregularity is attended by variations in the core size and shape and results from changes in the core position. The authors conclude that functionally determined reentrant activity in the heart may be the result of spiral waves of propagation and that local spatiotemporal irregularities in the activation pattern are the result of changes in the core position.

VL - 24 Suppl UR - http://www.ncbi.nlm.nih.gov/pubmed/1552240 ER - TY - JOUR T1 - Stationary and drifting spiral waves of excitation in isolated cardiac muscle. JF - Nature Y1 - 1992 A1 - Davidenko, J M A1 - Pertsov, A V A1 - Salomonsz, R A1 - Baxter, Bill A1 - Jalife, J KW - Animals KW - Dogs KW - Heart KW - Mathematics KW - Membrane Potentials KW - Models, Biological KW - Myocardial Contraction KW - Sheep AB -

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 're-entrant excitation' 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.

VL - 355 UR - http://www.ncbi.nlm.nih.gov/pubmed/1731248 IS - 6358 ER -