Pulmonary vein triggers, focal sources, rotors and atrial cardiomyopathy: implications for the choice of the most effective ablation therapy.

Understanding of the pathophysiological mechanism(s) underlying atrial fibrillation (AF) is the foundation on which current ablation strategies are built. In the vast majority of patients with paroxysmal AF, the ablation procedure should target the pulmonary veins. In patients with nonparoxysmal AF, however, pulmonary vein isolation alone seems to be insufficient to prevent the arrhythmia. Several recent clinical trials have investigated the concept that rotors (re-entry based on a meandering central core from which spiral waves emanate) might be the mechanism responsible for sustaining AF. Ablation of these localized AF sources is an important step towards substrate-driven procedures in persistent AF. Hybrid AF ablation procedures, based on the integration of endocardial transcatheter and epicardial off-pump surgical techniques, have been introduced to overcome their mutual shortcomings. The long-term results are encouraging, especially in currently challenging settings such as nonparoxysmal AF and failed endocardial catheter ablation procedures.

Phase resetting and annihilation of pacemaker activity in cardiac tissue.

Spontaneous rhythmic activity in isolated cardiac pacemaker cells can be terminated by a brief, subthreshold, depolarizing or hyperpolarizing perturbation of the proper magnitude applied at a specific point in the pacemaker cycle. Evidence is provided in support of a topological theory of the existence of a "singular" point in cardiac oscillators.

Action potential characteristics and arrhythmogenic properties of the cardiac conduction system of the murine heart.

Studies have characterized conduction velocity in the right and left bundle branches (RBB, LBB) of normal and genetically engineered mice. However, no information is available on the action potential characteristics of the specialized conduction system (SCS). We have used microelectrode techniques to characterize action potential properties of the murine SCS, as well as epicardial and endocardial muscle preparations for comparison. In the RBB, action potential duration at 50%, 70%, and 90% repolarization (APD(50,70,90)) was 6+/-0.7, 35+/-6, and 90+/-7 ms, respectively. Maximum upstroke velocity (dV/dt(max)) was 153+/-14 V/s, and conduction velocity averaged 0.85+/-0.2 m/s. APD(90) was longer in the Purkinje network of fibers (web) than in the RBB (P<0.01). Web APD(50) was longer in the left than in the right ventricle (P<0.05). Yet, web APD(90) was longer in the right than in the left ventricle (P<0.001). APD(50,70) was significantly longer in the endocardial than in the epicardial (P<0.001; P<0.003). APD(90) in the epicardial and endocardial was shorter than in the RBB ( approximately 36 ms versus approximately 100 ms). Spontaneous electrical oscillations in phase 2 of the SCS occasionally resulted in early afterdepolarizations. These results demonstrate that APDs in the murine SCS are significantly ( approximately 2-fold) longer than in the myocardium and implicate the role of the murine SCS in arrhythmias. The differences should have important implications in the use of the mouse heart to study excitation, propagation, and arrhythmias.

High-resolution optical mapping of the right bundle branch in connexin40 knockout mice reveals slow conduction in the specialized conduction system.

Connexin40 (Cx40) is a major gap junction protein that is expressed in the His-Purkinje system and thought to be a critical determinant of cell-to-cell communication and conduction of electrical impulses. Video maps of the ventricular epicardium and the proximal segment of the right bundle branch (RBB) were obtained using a high-speed CCD camera while simultaneously recording volume-conducted ECGs. In Cx40(-/-) mice, the PR interval was prolonged (47.4+/-1.4 in wild-type [WT] [n=6] and 57.5+/-2.8 in Cx40(-/-) [n=6]; P<0.01). WT ventricular epicardial activation was characterized by focused breakthroughs that originated first on the right ventricle (RV) and then the left ventricle (LV). In Cx40(-/-) hearts, the RV breakthrough occurred after the LV breakthrough. Additionally, Cx40(-/-) mice showed RV breakthrough times that were significantly delayed with respect to QRS complex onset (3.7+/-0.7 ms in WT [n=6] and 6.5+/-0.7 ms in Cx40(-/-) [n=6]; P<0.01), whereas LV breakthrough times did not change. Conduction velocity measurements from optical mapping of the RBB revealed slow conduction in Cx40(-/-) mice (74.5+/-3 cm/s in WT [n=7] and 43.7+/-6 cm/s in Cx40(-/-) [n=7]; P<0.01). In addition, simultaneous ECG records demonstrated significant delays in Cx40(-/-) RBB activation time with respect to P time (P-RBB time; 41.6+/-1.9 ms in WT [n=7] and 55.1+/-1.3 ms in [n=7]; P<0.01). These data represent the first direct demonstration of conduction defects in the specialized conduction system of Cx40(-/-) mice and provide new insight into the role of gap junctions in cardiac impulse propagation.

Distribution of excitation frequencies on the epicardial and endocardial surfaces of fibrillating ventricular wall of the sheep heart.

Tissue heterogeneities may play an important role in the mechanism of ventricular tachycardia (VT) and fibrillation (VF) and can lead to a complex spatial distribution of excitation frequencies. Here we used optical mapping and Fourier analysis to determine the distribution of excitation frequencies in >20 000 sites of fibrillating ventricular tissue. Our objective was to use such a distribution as a tool to quantify the degree of organization during VF. Fourteen episodes of VT/VF were induced via rapid pacing in 9 isolated, coronary perfused, and superfused sheep ventricular slabs (3x3 cm(2)). A dual-camera video-imaging system was used for simultaneous optical recordings from the entire epi- and endocardial surfaces. The local frequencies of excitation were determined at each pixel and displayed as dominant frequency (DF) maps. A typical DF map consisted of several (8.2+/-3.6) discrete areas (domains) with a uniform DF within each domain. The DFs in adjacent domains were often in 1:2, 3:4, or 4:5 ratios, which was shown to be a result of an intermittent Wenckebach-like conduction block at the domain boundaries. The domain patterns were relatively stable and could persist from several seconds to several minutes. The complexity in the organization of the domains, the number of domains, and the dispersion of frequencies increased with the rate of the arrhythmia. Domain patterns on the epicardial and endocardial surfaces were not correlated. Sustained epicardial or endocardial reentry was observed in only 3 episodes. Observed frequency patterns during VT/VF suggest that the underlying mechanism may be a sustained intramural reentrant source interacting with tissue heterogeneities.

Rectification of the background potassium current: a determinant of rotor dynamics in ventricular fibrillation.

Ventricular fibrillation (VF) is the leading cause of sudden cardiac death. Yet, the mechanisms of VF remain elusive. Pixel-by-pixel spectral analysis of optical signals was carried out in video imaging experiments using a potentiometric dye in the Langendorff-perfused guinea pig heart. Dominant frequencies (peak with maximal power) were distributed throughout the ventricles in clearly demarcated domains. The fastest domain (25 to 32 Hz) was always on the anterior left ventricular (LV) wall and was shown to result from persistent rotor activity. Intermittent block and breakage of wavefronts at specific locations in the periphery of such rotors were responsible for the domain organization. Patch-clamping of ventricular myocytes from the LV and the right ventricle (RV) demonstrated an LV-to-RV drop in the amplitude of the outward component of the background rectifier current (I(B)). Computer simulations suggested that rotor stability in LV resulted from relatively small rectification of I(B) (presumably I(K1)), whereas instability, termination, and wavebreaks in RV were a consequence of strong rectification. This study provides new evidence in the isolated guinea pig heart that a persistent high-frequency rotor in the LV maintains VF, and that spatially distributed gradients in I(K1) density represent a robust ionic mechanism for rotor stabilization and wavefront fragmentation.

Null mutation of connexin43 causes slow propagation of ventricular activation in the late stages of mouse embryonic development.

Connexin43 (Cx43) is the principal connexin isoform in the mouse ventricle, where it is thought to provide electrical coupling between cells. Knocking out this gene results in anatomic malformations that nevertheless allow for survival through early neonatal life. We examined electrical wave propagation in the left (LV) and right (RV) ventricles of isolated Cx43 null mutated (Cx43(-/-)), heterozygous (Cx43(+/)(-)), and wild-type (WT) embryos using high-resolution mapping of voltage-sensitive dye fluorescence. Consistent with the compensating presence of the other connexins, no reduction in propagation velocity was seen in Cx43(-/-) ventricles at postcoital day (dpc) 12.5 compared with WT or Cx43(+/)(-) ventricles. A gross reduction in conduction velocity was seen in the RV at 15.5 dpc (in cm/second, mean [1 SE confidence interval], WT 9.9 [8.7 to 11.2], Cx43(+/)(-) 9.9 [9.0 to 10.9], and Cx43(-/-) 2.2 [1.8 to 2.7; P<0.005]) and in both ventricles at 17.5 dpc (in RV, WT 8.4 [7.6 to 9.3], Cx43(+/)(-) 8.7 [8.1 to 9.3], and Cx43(-/-) 1.1 [0.1 to 1.3; P<0.005]; in LV, WT 10.1 [9.4 to 10.7], Cx43(+/)(-) 8.3 [7.8 to 8.9], and Cx43(-/-) 1.7 [1.3 to 2.1; P<0.005]) corresponding with the downregulation of Cx40. Cx40 and Cx45 mRNAs were detectable in ventricular homogenates even at 17.5 dpc, probably accounting for the residual conduction function. Neonatal knockout hearts were arrhythmic in vivo as well as ex vivo. This study demonstrates the contribution of Cx43 to the electrical function of the developing mouse heart and the essential role of this gene in maintaining heart rhythm in postnatal life.

Stable microreentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart.

BACKGROUND: Atrial fibrillation (AF) has traditionally been described as aperiodic or random. Yet, ongoing sources of high-frequency periodic activity have recently been suggested to underlie AF in the sheep heart. Our objective was to use a combination of optical and bipolar electrode recordings to identify sites of periodic activity during AF and elucidate their mechanism. METHODS AND RESULTS: AF was induced by rapid pacing in the presence of 0.1 to 0.5 micromol/L acetylcholine in 7 Langendorff-perfused sheep hearts. We used simultaneous optical mapping of the right and left atria (RA and LA) and frequency sampling of optical and bipolar electrode recordings (including a roving electrode) to identify sites having the highest dominant frequency (DF). Rotors were identified from optical recordings, and their rotation period, core area, and perimeter were measured. In all, 35 AF episodes were analyzed. Mean LA and RA DFs were 14.7+/-3.8 and 10.3+/-2.1 Hz, respectively. Spatiotemporal periodicity was seen in the LA during all episodes. In 5 of 7 experiments, a single site having periodic activity at the highest DF was localized. The highest DF was most often (80%) localized to the posterior LA, near or at the pulmonary vein ostium. Rotors (n=14) were localized on the LA. The mean core perimeter and area were 10.4+/-2.8 mm and 3.8+/-2.8 mm(2), respectively. CONCLUSIONS: Frequency sampling allows rapid identification of discrete sites of high-frequency periodic activity during AF. Stable microreentrant sources are the most likely underlying mechanism of AF in this model.

Left-to-right gradient of atrial frequencies during acute atrial fibrillation in the isolated sheep heart.

BACKGROUND: Recent studies demonstrated spatiotemporal organization in atrial fibrillation (AF). We hypothesized that waves emanating from sources in the left atrium (LA) undergo fragmentation, resulting in left-to-right frequency gradient. Our objective was to characterize impulse propagation across Bachmann's bundle (BB) and the inferoposterior pathway (IPP) during AF. METHODS AND RESULTS: In 13 Langendorff-perfused sheep hearts, AF was induced in the presence of acetylcholine (ACh). Fast Fourier transform of optical and bipolar electrode recordings was performed. Frequency-dependent changes in the left-to-right dominant frequency (DF) gradient were studied by perfusing D600 (2 micromol/L) and by increasing ACh concentration from 0.2 to 0.5 micromol/L. BB and IPP were subsequently ablated. At baseline, a left-to-right decrease in DFs occurred along BB and IPP, resulting in an LA-right atrium (RA) frequency gradient of 5.7+/-1.4 HZ: Left-to-right impulse propagation was present in 81+/-5% and 80+/-10% of cases along BB and IPP, respectively. D600 decreased the highest LA frequency from 19.7+/-4.4 to 16.2+/-3.9 Hz (P<0.01) and raised RA DF from 8.6+/-2.0 to 10.7+/-1.8 Hz (P<0.05). An increase in ACh concentration increased the LA-RA frequency gradient from 4.9+/-1.8 to 8.9+/-1.8 Hz (P<0.05). Ablation of BB and IPP decreased RA DF from 10.9+/-1.2 to 9.0+/-1.5 Hz (P<0.01) without affecting LA DF (16.8+/-1.5 versus 16.9+/-1.8 Hz, P=NS). CONCLUSIONS: Left-to-right impulse propagation and frequency-dependent changes in the LA-RA frequency gradient during AF strongly support the hypothesis that this arrhythmia is the result of high-frequency periodic sources in the LA, with fibrillatory conduction away from such sources.

Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart.

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.

Spatial and temporal organization in ventricular fibrillation.

Ventricular fibrillation (VF) is the leading heart rhythm alteration that results in sudden cardiac death, yet the detailed mechanisms of the arrhythmia remain elusive. Fibrillation has been defined as "turbulent" cardiac electrical activity, which conjures up the idea of totally random and disorganized activation of the ventricles. I review theoretical concepts and recently published results based on a newly developed algorithm, "two-dimensional phase mapping," which demonstrates that VF is not random and may be analyzed quantitatively. The approach is based on video imaging of voltage-sensitive dye fluorescence to record transmembrane potential simultaneously from 20,000 sites on the epicardial surface of rabbit and sheep ventricles. During VF, activity shows a strong periodic component centered near approximately 500 beats/min. Phase maps reveal that VF depends on the organization of electrical waves around a small number of "phase singularities" that have relatively short lifespans and form as a result of interactions of wavefronts with obstacles in their paths. Overall, the evidence demonstrates that there is a high degree of temporal and spatial organization in cardiac fibrillation. The results may pave the way for a better understanding of the mechanisms of VF in normal, as well as in diseased, hearts.

Mechanisms underlying ventricular tachycardia and its transition to ventricular fibrillation in the structurally normal heart.

Reentrant ventricular tachycardia (VT) is the most common sustained arrhythmia leading to ventricular fibrillation (VF). However, despite more than a century of research, the mechanism(s) of the conversion from reentrant VT to VF have not been elucidated. Based on their different electrocardiographic appearance, reentrant VT and VF have traditionally been thought of as resulting from two widely different mechanisms. Whereas VT is seen as a rapid but well organized process whereby the excitation wave rotates about a single well-defined circuit, fibrillation has been described as turbulent cardiac electrical activity, resulting from the random and aperiodic propagation of multiple independent wavelets throughout the cardiac muscle. Recently, the application of concepts derived from the theory of non-linear dynamics to the problem of wave propagation in the heart and the advent of modern high-resolution mapping techniques, have led some investigators to view VT and VF in terms of a single mechanism, whereby the self-organization of electrical waves forms 'rotors' that give rise to rapidly rotating spiral waves and results in either VT or VF, depending on the frequency of rotation and on the interaction of wave fronts with the cardiac muscle. As such, monomorphic VT is thought to result from a stationary rotor, whose frequency of rotation is within a range that allows 1:1 excitation of both ventricles. On the other hand, VF is thought to result from either a single rapidly drifting rotor, or a stationary rotor whose frequency of excitation is exceedingly high, thus resulting in multiple areas of intermittent block and giving rise to complex patterns of propagation with both deterministic and stochastic components. This article reviews the prevailing theories for the maintenance of VF, and discusses recently proposed mechanisms underlying transitions between VT and VF.

Effects of diacetyl monoxime on the electrical properties of sheep and guinea pig ventricular muscle.

OBJECTIVE: Diacetyl monoxime (DAM), a nucleophilic agent with "phosphatase-like" activity, has been found to effectively and reversibly block cardiac muscle contraction, while the cells remain capable of generating transmembrane action potentials. The aim of this study was to characterise the effects of DAM on the electrical properties of cardiac muscle. METHODS: Sheep epicardial muscle, guinea pig papillary muscle, and guinea pig ventricular myocytes were studied using conventional microelectrode techniques as well as single electrode current and voltage clamp techniques. RESULTS: DAM (5-20 mM) decreased action potential duration at 50% and 90% repolarisation levels (APD50, APD90) and refractory period in a dose dependent manner without causing significant changes in action potential amplitude, maximum upstroke velocity, or resting membrane potential. DAM induced a slight decrease in action potential conduction velocity in both the longitudinal and transverse directions, but on average the conduction velocity recorded in the presence of the drug was not significantly different from control. The time course of the APD restitution curve was not significantly changed but the frequency dependent APD variations were reduced. The ionic bases for these changes were studied in guinea pig ventricular myocytes. As with the results obtained in tissue preparations, DAM 15 mM decreased APD50 and APD90 by 35% and 29%, respectively. Under voltage clamp conditions, DAM led to a 35% reduction of ICa. The delayed rectifier IK current and the inward rectifier background current were also partially depressed by DAM but to a lesser extent. All of these effects were reversible upon washout. CONCLUSIONS: Aside from its well known effect as an electromechanical uncoupler, DAM causes a small, reversible, and non-selective reduction of several membrane conductances. Provided such effects are taken into consideration, DAM is a valuable tool in electrophysiological studies.

Dynamics of wavelets and their role in atrial fibrillation in the isolated sheep heart.

BACKGROUND: The multiple wavelet hypothesis is the most commonly accepted mechanism underlying atrial fibrillation (AF). However, high frequency periodic activity has recently been suggested to underlie atrial fibrillation in the isolated sheep heart. We hypothesized that in this model, multiple wavelets during AF are generated by fibrillatory conduction away from periodic sources and by themselves may not be essential for AF maintenance. METHODS AND RESULTS: We have used a new method of phase mapping that enables identification of phase singularities (PSs), which flank individual wavelets during sustained AF. The approach enabled characterization of the initiation, termination, and lifespan of wavelets formed as a result of wavebreaks, which are created by the interaction of wave fronts with functional and anatomical obstacles in their path. AF was induced in six Langendorff-perfused sheep hearts in the presence of acetylcholine. High resolution video imaging was utilized in the presence of a voltage sensitive dye; two-dimensional phase maps were constructed from optical recordings. The major results were as follows: (1) the critical inter-PS/wavelet distance for the formation of rotors was 4 mm, (2) the spatial distribution of wavelets/PSs was non-random. (3) the lifespan of PSs/wavelets was short; 98% of PSs/wavelets existed for < 1 rotation, and (4) the mean number of waves that entered our mapping field (15.7 +/- 1.6) exceeded the mean number of waves that exited it (9.7 +/- 1.5; P < 0.001). CONCLUSIONS: Our results strongly suggest that multiple wavelets may result from breakup of high frequency organized waves in the isolated Langendorff-perfused sheep heart, and as such are not a robust mechanism for the maintenance of AF in our model.

A biologic model of parasystole.

The electrotonic interactions of a parasystolic pacemaker with ventricular responses to the normal pacemaker across an area of depressed excitability were simulated in a model consisting of strands of canine Purkinje fibers mounted in a sucrose gap preparation. Experiments were conducted to study the patterns of ectopic activity that result from entrainment of the "ectopic" pacemaker (EP) on one side of the sucrose gap by evoked responses (sn) on the other side of the gap. When one-way conduction ("entrance block") was established, manipulations of the SN frequency and of the impedance between the two outer chambers resulted in periods of silence, concealed or manifest bigeminy, trigeminy and quadrigeminy, and periods of more complex patterns of group beating as the entrainment ratios changed. The results confirm the predictions of the previously described mathematical model that these patterns depend on the magnitude of the electrotonic influence of SN on the EP cycle length and also on the ratio of the intrinsic frequencies. These studies should help to distinguish between reentrant and parasystolic mechanisms in clinical arrhythmias.

Modulated parasystole as a mechanism of ventricular ectopic activity leading to ventricular fibrillation.

The electrocardiograms of 2 patients with frequent premature ventricular complexes characterized by variable coupling intervals and fusions with sinus activations were analyzed according to the modulated parasystole and reflection hypotheses of Moe et al. In addition, the ectopic activity was associated with couplets, tachycardia and ventricular fibrillation. Departures from the "classic" criteria of parasystole could not be explained satisfactorily if a completely protected (insulated) pacemaker was assumed. In each instance a triphasic response curve could be constructed, suggesting that modulated parasystole was the mechanism common to both patients. Couplets and runs of ventricular tachycardia were ascribed to single and repetitive reflection, respectively, in the presence of supernormal excitability of the ectopic pacemaker, the ventricle or both. In these patients, fibrillation probably resulted from spatial nonuniformity of the ventricular response to the reflected event during a phase of vulnerability. This study suggests that modulated parasystole in the presence of supernormal excitability may lead to very severe arrhythmias and trigger ventricular fibrillation. In the clinical setting, such patients may be misdiagnosed because of atypical features.

Irregular dynamics of excitation in biologic and mathematical models of cardiac cells.

Excitation and impulse propagation in cardiac tissues are dependent on the heart rate and can occur in extremely complex patterns. In this chapter we present the results of Purkinje fiber experiments and of computer simulations using an ionic (Beeler & Reuter) model for the ventricular cell. We have studied the global rate-dependent behavior of cardiac cells through a systematic analysis of their response to single as well as repetitive depolarizing stimuli, and determined the role of nonlinearity in the mechanism(s) of their behaviors. To this end, we devised an analytical difference equation model of cardiac cell excitation which could be used to predict simple as well as chaotic behavior of both the Purkinje fiber and the Beeler & Reuter cell, depending on the stimulation rate. Both experimental and modeling results suggest that the presence of supernormal recovery in cell excitability establishes sufficient nonlinearity so that, during repetitive stimulation, the dynamics of cell response may be regular and predictable when the stimulus magnitude is either very small or very large, or they may be chaotic and very unpredictable when the stimulus magnitude is intermediate. The overall results suggest that the application of nonlinear systems theory to electrophysiology may have importance in the understanding of cardiac rhythm and conduction disturbances, and may have clinical implications as well.

Shaping of a scroll wave filament by cardiac fibers.

Scroll waves of electrical excitation in heart tissue are implicated in the development of lethal cardiac arrhythmias. Here we study the relation between the geometry of myocardial fibers and the equilibrium shape of a scroll wave filament. Our theory accommodates a wide class of myocardial models with spatially varying diffusivity tensor, adjusted to fit fiber geometry. We analytically predict the exact equilibrium shapes of the filaments. The major conclusion is that the filament shape is a compromise between a straight line and full alignment with the fibers. The degree of alignment increases with the anisotropy ratio. The results, being purely geometrical, are independent of details of ionic membrane mechanisms. Our theoretical predictions have been verified to excellent accuracy by numerically simulating the stable equilibration of a scroll filament in a model of the FitzHugh-Nagumo type.

Ventricular fibrillation and atrial fibrillation are two different beasts.

Although the mechanisms of fibrillation are no doubt multi-faceted, the geometry of the heart may play a major role in the dynamics of wave propagation during fibrillation [A. T. Winfree, Science 266, 1003-1006 (1994)]. The ventricles are thick chambers made up of sheets of parallel muscle fibers with the direction of fibers rotating across the ventricular walls (rotational anisotropy). The thick walls of the ventricles allow reentry to develop transmurally, provided the wavelength is sufficiently small. Depending on the kinetics of heart cells, the dynamics of rotating waves in three dimensions may be fundamentally different than in two dimensions, leading to destabilization of reentry and ventricular fibrillation (VF) in thick ventricles. The atria have an intricate geometry comprised of a thin sheet of cardiac tissue attached to a very complex network of pectinate muscles. The branching geometry of the pectinate muscles may lead to destabilization of two-dimensional reentry via "long-distance" electrical connections giving rise to atrial fibrillation (AF). Therefore, although fibrillation occurs via complex three-dimensional wave propagation in the ventricles and the atria, the underlying mechanisms and factors that sustain VF and AF are probably different.(c) 1998 American Institute of Physics.