Mother Rotor Research Articles

Electrophysiology of Hypokalemia and Hyperkalemia.

Electrophysiology of Hypokalemia and Hyperkalemia.

49-02: Arrhythmia dynamics in heterogeneous fibrotic tissue is determined by the regions with the highest degree of fibrosis

Fibrosis is an important consequence of tissue remodeling and occurs in many forms of heart disease. Fibrosis is considered as an important risk factor for cardiac arrhythmias. It was also suggested that spatial distribution of fibrosis may play an important role in arrhythmia onset. Here, we investigate how spatial heterogeneity of fibrosis affects arrhythmia onset using numerical methods. Methods: We used a TNNP,TP06 (Ten Tusscher, Panfilov 2006) model for human ventricular cells. We generate various tissue textures that differ by the mean amount of fibrosis, the degree of heterogeneity and the spatial size of heterogeneity. We study the onset of arrhythmias using a burst pacing protocol. We also study dynamics of existing spiral waves in heterogeneous fibrotic tissue. Results: We show that the onset of arrhythmias increases with increased degree and spatial size of heterogeneity. The observed dependency can be explained by the presence of patches with maximal fibrosis in heterogeneous fibrotic tissue. Similarly, the period of arrhythmia increases with the increase in the degree of heterogeneity and is also determined by the patches with maximal fibrosis. The observed effects can be explained by attraction of rotors to the regions with maximal degree of fibrosis. To show that such attraction occurs we simulated behaviour of a spiral wave rotating at some distance from a fibrotic region mimicking the situation in a peri-infarct zone. We found that the spiral wave will always be attracted by the fibrotic region. We provide data on characteristic time of attraction and necessary size of the heterogeneity. We also study the mechanism of arrhythmia in fibrotic tissue by performing ablations of the induced fibrillatory patterns. We show that the fibrillation is mostly of the mother rotor type. However, if the tissue size increases it can become of the a multiple wavelet type as well. Conclusions: The most important factor determining the formation and dynamics of arrhythmia in heterogeneous fibrotic tissue is the value of maximal local fibrosis. The patches with maximal fibrosis in heterogeneous tissue attract rotors.

Electrophysiological Rotor Ablation in In-Silico Modeling of Atrial Fibrillation: Comparisons with Dominant Frequency, Shannon Entropy, and Phase Singularity.

BackgroundAlthough rotors have been considered among the drivers of atrial fibrillation (AF), the rotor definition is inconsistent. We evaluated the nature of rotors in 2D and 3D in- silico models of persistent AF (PeAF) by analyzing phase singularity (PS), dominant frequency (DF), Shannon entropy (ShEn), and complex fractionated atrial electrogram cycle length (CFAE-CL) and their ablation.MethodsMother rotor was spatiotemporally defined as stationary reentries with a meandering tip remaining within half the wavelength and lasting longer than 5 s. We generated 2D- and 3D-maps of the PS, DF, ShEn, and CFAE-CL during AF. The spatial correlations and ablation outcomes targeting each parameter were analyzed.Results1. In the 2D PeAF model, we observed a mother rotor that matched relatively well with DF (>9 Hz, 71.0%, p<0.001), ShEn (upper 2.5%, 33.2%, p<0.001), and CFAE-CL (lower 2.5%, 23.7%, p<0.001). 2. The 3D-PeAF model also showed mother rotors that had spatial correlations with DF (>5.5 Hz, 39.7%, p<0.001), ShEn (upper 8.5%, 15.1%, p <0.001), and CFAE (lower 8.5%, 8.0%, p = 0.002). 3. In both the 2D and 3D models, virtual ablation targeting the upper 5% of the DF terminated AF within 20 s, but not the ablations based on long-lasting PS, high ShEn area, or lower CFAE-CL area.ConclusionMother rotors were observed in both 2D and 3D human AF models. Rotor locations were well represented by DF, and their virtual ablation altered wave dynamics and terminated AF.

Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism.

Myocardial fibrosis is an important risk factor for cardiac arrhythmias. Previous experimental and numerical studies have shown that the texture and spatial distribution of fibrosis may play an important role in arrhythmia onset. Here, we investigate how spatial heterogeneity of fibrosis affects arrhythmia onset using numerical methods. We generate various tissue textures that differ by the mean amount of fibrosis, the degree of heterogeneity and the characteristic size of heterogeneity. We study the onset of arrhythmias using a burst pacing protocol. We confirm that spatial heterogeneity of fibrosis increases the probability of arrhythmia induction. This effect is more pronounced with the increase of both the spatial size and the degree of heterogeneity. The induced arrhythmias have a regular structure with the period being mostly determined by the maximal local fibrosis level. We perform ablations of the induced fibrillatory patterns to classify their type. We show that in fibrotic tissue fibrillation is usually of the mother rotor type but becomes of the multiple wavelet type with increase in tissue size. Overall, we conclude that the most important factor determining the formation and dynamics of arrhythmia in heterogeneous fibrotic tissue is the value of maximal local fibrosis.

Electrical wave propagation in an anisotropic model of the left ventricle based on analytical description of cardiac architecture.

We develop a numerical approach based on our recent analytical model of fiber structure in the left ventricle of the human heart. A special curvilinear coordinate system is proposed to analytically include realistic ventricular shape and myofiber directions. With this anatomical model, electrophysiological simulations can be performed on a rectangular coordinate grid. We apply our method to study the effect of fiber rotation and electrical anisotropy of cardiac tissue (i.e., the ratio of the conductivity coefficients along and across the myocardial fibers) on wave propagation using the ten Tusscher–Panfilov (2006) ionic model for human ventricular cells. We show that fiber rotation increases the speed of cardiac activation and attenuates the effects of anisotropy. Our results show that the fiber rotation in the heart is an important factor underlying cardiac excitation. We also study scroll wave dynamics in our model and show the drift of a scroll wave filament whose velocity depends non-monotonically on the fiber rotation angle; the period of scroll wave rotation decreases with an increase of the fiber rotation angle; an increase in anisotropy may cause the breakup of a scroll wave, similar to the mother rotor mechanism of ventricular fibrillation.

Drifting Through the Beehive

Spiral waves are thought to underliemany heart arrhythmias, includingfibrillation (1,2). Some of the earliestexperimental recordings of spiralwaves indicated that sometimes theydrift (3), meaning that the core of thespiral wave not only meanders in aspirographlike pattern but also amblesalong, on average, in one direction.This is not unlike the motion of anelectron in a copper wire, with arandom thermal motion—akin to themeandering of a spiral wave, but lessorganized—and a slower drift speed inthedirectionofanappliedelectricfield.What causes the drift of a spiral wave?One important factor is heterogeneityof tissue properties. The resulting drifthas two components: one along thedirection of the heterogeneity, andanother perpendicular to it. Consider aspiral wave rotating in the x-y plane. Ifthe tissue properties vary with x, thenthecoreofthespiralwavecandriftpar-allel to the y axis. Whether it is in thepositive or negative direction alongthis axis depends on whether the spiralwave rotates clockwise or counter-clockwise (4). The core can also driftparallel to the x axis, usually towardthe region of longest action potentialduration (5). In this issue of theBiophysical Journal, Calvo et al. (6)use computer simulations to analyzethe drift of a spiral wave in the atrium,where there exists a marked gradientof tissue properties.In their title, Calvo et al. (6) labeltheirmodelasrepresentingatrialfibril-lation,althoughperhaps‘‘atrialflutter’’is the more appropriate term. Youropinion about the importance of thissimulation for atrial fibrillation maydepend on your point of view abouthow fibrillation is sustained. Rogersand Ideker (7) compare the competinghypothesesbyinvokingtwometaphors:a rabbit warren and a beehive. In therabbit warren analogy, parent wave-fronts break up into daughter wave-fronts, which break up again andagain, like ‘‘rabbits breeding in awarren’’ (7). Fenton et al. (8) have pre-formed elegant simulations illustratingthis type of behavior. The alternativeview is that there exists a mother rotor,the‘‘queenbee’’governingthebeehive,acting as the source of wave fronts thatsometimesfailorbreakupastheyprop-agate outward (8). This academicdebate over the mechanism that sus-tains atrial fibrillation has a transla-tional counterpart: investigators haveobtained clinical data that supportboth the rabbit warren (9) and thebeehive (10) hypotheses. If you favorthe second metaphor, then for you, thestudy of Calvo et al. (6) examines howthe mother rotor drifts through thebeehive.The most important membrane cur-rent distributed heterogeneously in thestudy of Calvo et al. is the time-inde-pendent inward rectifier, I

Different types of long-duration ventricular fibrillation: Can they be identified by electrocardiography

We tested the hypothesis that after 2 minutes of ventricular fibrillation (VF), periods of highly organized activations occur on the endocardium, arising from an intramural mother rotor or triggered activity originating in the Purkinje fibers. In 6 anesthetized dogs, we recorded electrically induced VF from two-thirds of the endocardium with a 64-electrode basket catheter. In another 12 dogs, the study was repeated with the addition of the early afterdepolarization blocker pinacidil in 6 animals and the delayed afterdepolarization blocker flunarizine in the other 6 animals. We found that, in addition to periods of disorganized chaotic activation (type I pattern), at between 3 and 7 minutes of VF, 2 highly organized patterns were observed (type II pattern, regular activity and type III pattern, triggered activity). When present, these patterns were observed in all 64 electrodes simultaneously. Type II arises from the apex and may be an intramural mother rotor and type III arises focally in Purkinje fibers and may be caused by early afterdepolarizations. The optimal defibrillation strategy may be different for the 3 different VF patterns. Therefore, it is important to determine if these 3 patterns can be differentiated from the body surface electrocardiogram.

Epicardial Ablation of Rotors Suppresses Inducibility of Acetylcholine-Induced Atrial Fibrillation in Left Pulmonary Vein–Left Atrium Preparations in a Beagle Heart Failure Model

The purpose of this study was to provide direct evidences that rotor ablation suppresses atrial fibrillation (AF) inducibility. Micro-re-entrant wavefronts have been suggested to serve as sources of rapid activations during AF. Whether AF inducibility is suppressed by elimination of rotors remains unknown. We used optical mapping to study Langendorff-perfused left pulmonary vein (PV)-left atrium (LA) preparations from 13 dogs with pacing-induced heart failure. Atrial arrhythmias were induced by pacing and mapped during acetylcholine infusion (1 μmol/l). Rotors were identified from optical recordings. Epicardial ablation was performed targeting the rotor anchoring sites in preparations with sustained (>10 min) or incessant spontaneous AF. Non-rotor ablation was performed in 4 preparations. Repeated pacing was performed to test the AF inducibility after ablation. Sustained AF (n = 12) and incessant spontaneous AF (n = 1) were induced after acetylcholine infusion. Pulmonary vein focal discharge was found in 9 preparations (9.2 ± 4.2 beats/s), and rotor anchoring was found at the left superior PV-LA junction in 13 preparations (9.1 ± 4.6 beats/s) and at the ligament of Marshall-PV-LA junction in 1 preparation. Epicardial rotor ablation successfully inhibited the inducibility of sustained AF in 12 of 13 preparations (p < 0.01), including 4 with the maximal dominant frequency sites located on the PV-LA junctional rotor zones (direct elimination of mother rotors). The longest AF duration was shortened significantly by rotor ablation (Wilcoxon Z = 3.60, p = 0.002, n = 13), but not by non-rotor ablation (Wilcoxon Z = 1.00, p = 0.317, n = 4). Epicardial ablation of the rotor anchoring sites suppresses AF inducibility. The arrhythmogenicity at the maximal dominant frequency sites is directly/indirectly suppressed by the rotor ablation.

17 Quantification of spatial dynamics of cardiac arrhythmias

The 1987 Lambeth conventions identify an arrhythmia from time series recordings of cardiac electrical activity. All cardiac arrhythmias are spatio-temporal and involve anisotropic and orthotropic propagation in heterogeneous tissue. Spatial...

Mechanisms of Fibrillation: Neurogenic or Myogenic? Reentrant or Focal? Multiple or Single?: Still Puzzling After 160 Years of Inquiry

Mechanisms of Fibrillation: Neurogenic or Myogenic? Reentrant or Focal? Multiple or Single?: Still Puzzling After 160 Years of Inquiry

Termination of atrial fibrillation by flecainide: mechanistic insights from spectral analysis

This editorial refers to ‘Increase in organization index predicts atrial fibrillation termination with flecainide post-ablation: spectral analysis of intracardiac electrograms’ by J. Tuan et al ., on page 488. The pathophysiology of atrial fibrillation (AF) is complex and remains incompletely understood. Atrial fibrillation is usually initiated by rapidly discharging foci, often from within the pulmonary veins, which is then maintained by an abnormal left atrial substrate. Experimental evidence suggests that AF is driven by rapidly discharging foci and waves rotating around fixed structures (mother rotors).1 These drivers give rise to daughter wavelets which propagate around the atria giving the appearance of ‘fibrillatory conduction’. Recurrent paroxysms of AF cause structural and electrophysiological remodelling of the left atrium eventually allowing it to persist.2 Within hours, there are changes in ion channel expression which shorten action potential duration (APD) and effective refractory period (ERP).2 Ultrastructural changes beginning within days of onset of AF include left atrial fibrosis, accumulation of extracellular matrix, and reduced expression of connexin 40 reducing conduction velocity.2 Heterogeneity of refractory periods and zones of slow conduction promote re-entry and support wavelets propagating around the atria. Flecainide exerts its effect through blockade of sodium channels ( I Na) and potassium channels ( I K1 and I KAch), which reduces conduction velocity and increases APD and ERP, respectively.3 These changes have opposing effects on wavelength, which is a product of conduction velocity and ERP. An increase in ERP and AF cycle length was demonstrated in response to flecainide in a canine model of AF.4 A concomitant increase in size and decrease in the number of re-entry wavelets was observed on high-density epicardial mapping. The authors assumed that the prolongation of ERP was the predominant effect, and that re-entry was … *Corresponding author. Tel: +44 207 601 8639; fax: +44 207 601 8627, Email: r.schilling{at}qmul.ac.uk

A computational study of mother rotor VF in the human ventricles.

Sudden cardiac death is one of the major causes of death in the industrialized world. It is most often caused by a cardiac arrhythmia called ventricular fibrillation (VF). Despite its large social and economical impact, the mechanisms for VF in the human heart yet remain to be identified. Two of the most frequently discussed mechanisms observed in experiments with animal hearts are the multiple wavelet and mother rotor hypotheses. Most recordings of VF in animal hearts are consistent with the multiple wavelet mechanism. However, in animal hearts, mother rotor fibrillation has also been observed. For both multiple wavelet and mother rotor VF, cardiac heterogeneity plays an important role. Clinical data of action potential restitution measured from the surface of human hearts have been recently published. These in vivo data show a substantial degree of spatial heterogeneity. Using these clinical restitution data, we studied the dynamics of VF in the human heart using a heterogeneous computational model of human ventricles. We hypothesized that this observed heterogeneity can serve as a substrate for mother rotor fibrillation. We found that, based on these data, mother rotor VF can occur in the human heart and that ablation of the mother rotor terminates VF. Furthermore, we found that both mother rotor and multiple wavelet VF can occur in the same heart depending on the initial conditions at the onset of VF. We studied the organization of these two types of VF in terms of filament numbers, excitation periods, and frequency domains. We conclude that mother rotor fibrillation is a possible mechanism in the human heart.

Mechanisms of VF maintenance: Wandering wavelets, mother rotors, or foci

Ventricular fibrillation (VF), despite its declining incidence as a cause of sudden cardiac death, is still a major health problem. The underlying mechanisms for the maintenance of VF are still disputed. Studies suggest that VF is unlikely one static mechanism but rather a dynamic process of electrical derangement that changes with duration. The 2 principal proposed mechanisms of VF are multiple wavelets and mother rotors. Most studies of these proposed mechanisms for VF maintenance have been during the first minute of VF. However, the time to external defibrillation in the community and pre-hospital settings, where the majority of sudden cardiac death occurs, ranges from 4 to 10 min and the time to defibrillation seems crucial because the odds of survival worsen with delay. Recent studies during the first 10 min of VF suggest that Purkinje fibers are important in maintaining VF after the first 1 to 2 min, either as a part of a reentrant circuit or as a source of focal activations.

Isolated focus of ventricular fibrillation

Mechanisms underlying the initiation of ventricular tachycardia have been described as either rapidly firing focus initiated by triggered activity or automaticity, or a reentrant wavefront initiated by a premature ventricular depolarization. Ventricular fibrillation can occur after ventricular tachycardia; however, uncertainty exists concerning its mechanism, whether it is caused by multiple wavelets, mother rotor, or a combination of both. This report describes the finding of a spontaneously isolated focus of ultrarapid ventricular activity recorded and ablated in a patient with nonischemic cardiomyopathy and ventricular tachycardia.

Epicardial mapping of ventricular fibrillation over the posterior descending artery and left posterior papillary muscle of the swine heart

Recent studies suggest that during ventricular fibrillation (VF) epicardial vessels may be a site of conduction block and the posterior papillary muscle (PPM) in the left ventricle (LV) may be the location of a "mother rotor." The goal of this study was to obtain evidence to support or refute these possibilities. Epicardial activation over the posterior LV and right ventricle (RV) was mapped during the first 20 s of electrically induced VF in six open-chest pigs with a 504 electrode plaque covering a 20 cm(2) area centered over the posterior descending artery (PDA). The locations of epicardial breakthrough as well as reentry clustered in time and space during VF. Spatially, reentry occurred significantly more frequently over the LV than the RV in all 48 episodes, and breakthrough clustered near the PPM (p < 0.001). Significant temporal clustering occurred in 79% of breakthrough episodes and 100% of reentry episodes. These temporal clusters occurred at different times so that there was significantly less breakthrough when reentry was present (p < 0.0001). Conduction block occurred significantly more frequently near the PDA than elsewhere. The PDA is a site of epicardial block which may contribute to VF maintenance. Epicardial breakthrough clusters near the PPM. Reentry also clusters in space but at a separate site. The fact that breakthrough and reentry cluster at different locations and at different times supports the possibility of a drifting filament at the PPM so that at times reentry is present on the surface but at other times the reentrant wavefront breaks through to the epicardium.

Panoramic imaging reveals basic mechanisms of induction and termination of ventricular tachycardia in rabbit heart with chronic infarction: Implications for low-voltage cardioversion

Sudden cardiac death due to arrhythmia in the settings of chronic myocardial infarction (MI) is an important clinical problem. Arrhythmic risk post-MI continues indefinitely even if heart failure and acute ischemia are not present due to the anatomic substrate of the scar and border zone (BZ) tissue. The purpose of this study was to determine mechanisms of arrhythmia initiation and termination in a rabbit model of chronic MI. Ligation of the lateral division of the left circumflex artery was performed 72 +/- 29 days before acute experiments (n = 11). Flecainide (2.13 +/- 0.64 microM) was administered to promote sustained arrhythmias, which were induced with burst pacing or a multiple shock protocol (four pulses, 140-200 ms coupling interval). Panoramic optical mapping with blebbistatin (5 microM) revealed monomorphic ventricular tachycardia (VT) maintained by a single mother rotor (cycle length [CL] = 174.7 +/- 38.4 ms) as the primary mechanism of arrhythmia. Mother rotors were anchored to the scar or BZ for 16 of the 19 rotor locations recorded. Cardioversion thresholds (CVTs) were determined at various phases throughout the VT CL from external shock electrodes. CVTs were found to be phase dependent, and the maximum versus minimum CVT was 7.8 +/- 1.9 vs. 4.1 +/- 1.6 V/cm, respectively (P = .005). Antitachycardia pacing was found to be effective in only 2.7% of cases in this model. These results indicate that scar and BZ tissue heterogeneity provide the substrate for VT by attracting and stabilizing rotors. Additionally, a significant reduction in CVT may be achieved by appropriately timed shocks in which the shock-induced virtual electrode polarization interacts with the rotor to destabilize VT.

The Long and the Short of Long and Short Duration Ventricular Fibrillation

See related article, pages 1256–1264 The mechanisms behind the complex activation sequences during ventricular fibrillation (VF) have been the topic of intense research over many years. Experimental studies in animal models of VF, as well as clinical studies of human VF,1–8 have provided a wealth of data on the nature of electric activity in the fibrillating heart. Supplemented by computer simulations and a theoretical framework of wave propagation in excitable media,9,10 our community has amassed significant insights into the mechanisms that lead to the degradation of electric activity into VF and of VF maintenance. However, the majority of these studies have been devoted to VF mechanisms in the short time period after VF onset (short-duration VF, lasting less than 1 minute). In an episode of cardiac arrest outside of the hospital, the median time to delivery of the first defibrillation shock is 4.4 minutes,11 with VF episodes often lasting as long as 10 minutes (long-duration VF); over this period, the heart becomes ischemic while being subjected to excessively high excitation rates. Changes in the electrophysiological properties of the myocardium take place over these long-duration VF episodes. This is reflected in the altered outcome of a defibrillation shock, with survival rates decreasing rapidly with the increase in minutes spent in VF.12 Similarly, the guidelines for optimal resuscitation therapy differ depending on VF duration: immediate defibrillation is prescribed if time from VF onset is less than 4 or …

Mother rotor anchoring in branching tissue with heterogeneous membrane properties / Ankern von mother rotors in verzweigtem Gewebe mit inhomogenen Membraneigenschaften

Abstract Current understanding of atrial fibrillation is based on the co-existence of multiple re-entrant waves propagating randomly throughout the tissue. However, recent experimental results indicate that in many cases one or a small number of periodic, high-frequency re-entrant sources (mother rotors) can drive the arrhythmia. Owing to the high activation rate, mother rotors seem to be located in regions of shortened action potential duration. In this study a computer model of cardiac propagation was applied to investigate mechanisms leading to the formation and maintenance of such mother rotors. For this purpose, a region of short action potential duration was generated by varying the acetylcholine concentration across the tissue. A mother rotor initiated in the center of this region drifts away, and the activation terminates. If an additional heterogeneity such as a bundle is included into the model, a further drift mechanism directed to the bundle is observed and the rotor can be stabilized. Therefore, bundle insertions may play an important role in the maintenance of mother rotors. The influence of the driving rotor on the activation pattern was studied in a three-dimensional model of rectangular shape and a monolayer model of anatomically correct atrial geometry.

Spatial-temporal filter effect in a computer model study of ventricular fibrillation / Räumlicher und zeitlicher Filtereffekt in einer Computermodellstudie zum Herzkammerflimmern

Prediction of countershock success from ventricular fibrillation (VF) ECG is a major challenge in critical care medicine. Recent findings indicate that stable, high frequency mother rotors are one possible mechanism maintaining VF. A computer model study was performed to investigate how epicardiac sources are reflected in the ECG. In the cardiac tissues of two computer models - a model with cubic geometry and a simplified torso model with a left ventricle - a mother rotor was induced by increasing the potassium rectifier current. On the epicardium, the dominant frequency (DF) map revealed a constant DF of 23 Hz (cubic model) and 24.4 Hz (torso model) in the region of the mother rotor, respectively. A sharp drop of frequency (3-18 Hz in the cubic model and 12.4-18 Hz in the torso model) occurred in the surrounding epicardial tissue of chaotic fibrillatory conduction. While no organized pattern was observable on the body surface of the cubic model, the mother rotor frequency can be identified in the anterior surface of the torso model because of the chosen position of the mother rotor in the ventricle (shortest distance to the body surface). Nevertheless, the DFs were damped on the body surfaces of both models (4.6-8.5 Hz in the cubic model and 14.4-16.4 Hz in the torso model). Thus, it was shown in this computer model study that wave propagation transforms the spatial low pass filtering of the thorax into a temporal low pass. In contrast to the resistive-capacitive low pass filter formed by the tissue, this spatial-temporal low pass filter becomes effective at low frequencies (tens of Hertz). This effect damps the high frequency components arising from the heart and it hampers a direct observation of rapid, organized sources of VF in the ECGs, when in an emergency case an artifact-free recording is not possible.

Epicardial wavefronts arise from widely distributed transient sources during ventricular fibrillation in the isolated swine heart

It has been proposed that ventricular fibrillation (VF) waves emanate from stable localized sources, often called ‘mother rotors’. However, evidence for the existence of these rotors is conflicting. Using a new panoramic optical mapping system that can image nearly the entire ventricular epicardium, we recently excluded epicardial mother rotors as the drivers of Wiggers' stage II VF in the isolated swine heart. Furthermore, we were unable to find evidence that VF requires sustained intramural sources. The present study was designed to test the following hypotheses: (i) VF is driven by a specific region, and (ii) rotors that are long-lived, though not necessarily permanent, are the primary generators of VF wavefronts. Using panoramic optical mapping, we mapped VF wavefronts from six isolated swine hearts. Wavefronts were tracked to characterize their activation pathways and to locate their originating sources. We found that the wavefronts that participate in epicardial re-entry were not confined to a compact region; rather they activated the entire epicardial surface. New wavefronts feeding into the epicardial activation pattern were generated over the majority of the epicardium and almost all of them were associated with rotors or repetitive breakthrough patterns that lasted for less than 2 s. These findings indicate that epicardial wavefronts in this model are generated by many transitory epicardial sources distributed over the entire surface of the heart.