Activation Wavefront Research Articles

Wavefront-based models for inverse electrocardiography

We introduce two wavefront-based methods for the inverse problem of electrocardiography, which we term wavefront-based curve reconstruction (WBCR) and wavefront-based potential reconstruction (WBPR). In the WBCR approach, the epicardial activation wavefront is modeled as a curve evolving on the heart surface, with the evolution governed by factors derived phenomenologically from prior measured data. The body surface potential/wavefront relationship is modeled via an intermediate mapping of wavefront to epicardial potentials, again derived phenomenologically. In the WBPR approach, we iteratively construct an estimate of epicardial potentials from an estimated wavefront curve according to a simplified model and use it as an initial solution in a Tikhonov regularization scheme. Initial simulation results using measured canine epicardial data show considerable improvement in reconstructing activation wavefronts and epicardial potentials with respect to standard Tikhonov solutions. In particular the WBCR method accurately finds the anisotropic propagation early after epicardial pacing, and the WBPR method finds the wavefront (regions of sharp gradient of the potential) both accurately and with minimal smoothing.

Anodal Capture in Cardiac Resynchronization Therapy Implications for Device Programming

Right ventricular (RV) anodal capture (AC) has been reported in cardiac resynchronization therapy (CRT), when left ventricular (LV) pacing uses pseudobipolar (LV tip to RV proximal electrode) configuration. The aim of the study was to analyze the prevalence of AC and its implications for device programming. When AC occurred, the resulting QRS morphology was evaluated with the following pacing modes: (1) LV tip pacing plus RV AC, (2) Biventricular (BiV) pacing (i.e., both LV and RV tip pacing), and (3) BiV pacing plus RV AC. Several interventricular pacing (VV) intervals from 50 ms of LV preactivation to 30 ms of RV preactivation were tested in modes 2 and 3. From 38 consecutive patients, AC was achieved in 14 (in 74% of the pacemakers and in none of the defibrillators). LV tip pacing plus RV AC obtained narrower QRS than BiV pacing at all VV intervals in seven of the patients with AC (50%). When BiV pacing is combined with RV AC, it produced a ventricular depolarization through two wave fronts (one from the LV tip and the second from either the ring or the tip of the RV lead depending on the VV interval programmed). AC obtained the narrowest QRS of all tested pacing modes in a significant proportion of patients undergoing CRT. Though the stimulus was delivered from three sites (BiV pacing plus RV AC mode), only two wave fronts of ventricular activation were seen by ECG.

High‐Resolution Mapping Around the Eustachian Ridge During Typical Atrial Flutter

Although the reentrant circuit of typical atrial flutter (AFL) has been well recognized, the activation around the Eustachian ridge (ER) has not been fully characterized. The aim of this study was to delineate the activation patterns around the ER during typical AFL using high-resolution noncontact mapping. Fifty-three patients (M/F = 43/10, 62 +/- 14 years) with typical AFL were included. The high-resolution mapping of the right atrium using a noncontact mapping system during AFL and pacing from the coronary sinus (CS) was performed to evaluate the conduction through the ER. Three types of activation patterns around the ER could be classified according to the ER conduction during AFL and CS pacing. Type I (n = 21, M/F = 16/5, 61 +/- 13 years) exhibited conduction block at the ER during AFL and CS pacing. The local unipolar electrograms at the ER exhibited long double potentials (DPs) (109 +/- 12 ms, range 77-153 ms) during AFL and CS pacing (84 +/- 18 ms, range 48-129 ms). Type II (n = 8, M/F = 7/1, 61 +/- 15 years) exhibited conduction block at the ER during AFL, but conduction through the ER during CS pacing. The unipolar electrograms exhibited long DPs (119 +/- 12 ms, range 97-141 ms) at the ER during the tachycardia and an rS pattern during CS pacing. Type III (n = 24, M/F = 20/4, 61 +/- 16 years) exhibited an activation wavefront that passed along the ER, with the sinus venosa as the posterior barrier during AFL. During CS pacing, all cases exhibited conduction through the ER with an rS pattern. This study is the first to demonstrate the three patterns of activation along the ER during AFL and CS pacing. This finding suggested that the ER is an anatomic and functional barrier during typical AFL.

Evidence for Multiple Mechanisms in Human Ventricular Fibrillation

The mechanisms that sustain ventricular fibrillation (VF) in the human heart remain unclear. Experimental models have demonstrated either a periodic source (mother rotor) or multiple wavelets as the mechanism underlying VF. The aim of this study was to map electrical activity from the entire ventricular epicardium of human hearts to establish the relative roles of these mechanisms in sustaining early human VF. In 10 patients undergoing cardiac surgery, VF was induced by burst pacing, and 20 to 40 seconds of epicardial activity was sampled (1 kHz) with a sock containing 256 unipolar contact electrodes connected to a UnEmap system. Signals were interpolated from the electrode sites to a fine regular grid (100x100 points), and dominant frequencies (DFs) were calculated with a fast Fourier transform with a moving 4096-ms window (10-ms increments). Epicardial phase was calculated at each grid point with the Hilbert transform, and phase singularities and activation wavefronts were identified at 10-ms intervals. Early human VF was sustained by large coherent wavefronts punctuated by periods of disorganized wavelet behavior. The initial fitted DF intercept was 5.11 +/- 0.25 (mean +/- SE) Hz (P < 0.0001), and DF increased at a rate of 0.018 +/- 0.005 Hz/s (P < 0.01) during VF, whereas combinations of homogeneous, heterogeneous, static, and mobile DF domains were observed for each of the patients. Epicardial reentry was present in all fibrillating hearts, typically with low numbers of phase singularities. In some cases, persistent phase singularities interacted with multiple complex wavelets; in other cases, VF was driven at times by a single reentrant wave that swept the entire epicardium for several cycles. Our data support both the mother rotor and multiple wavelet mechanisms of VF, which do not appear to be mutually exclusive in the human heart.

P5-12: Wavefront width during human ventricular fibrillation

The mechanisms that sustain human ventricular fibrillation (VF) are controversial. The aim of this study was to determine the widths of activation wavefronts in the fibrillating human heart by mapping the entire ventricular epicardial surface.

The sequence of regional ventricular motion

The chronology of electrical events that mechanically activate the myocardium has been described as initiating at the level of the septum, spreading to the apex, then to the bodies of both ventricles and eventually to the base of the heart (apex-to base activation). It has recently been suggested that the myocardium is a single muscular band that conforms a double-loop helicoid. Contraction of the myocardium would follow the trajectory of the muscular fibers that originate at the pulmonary artery towards the body of the left ventricle and to the aorta (base-to apex contraction). This would explain the movements of the base of the heart and the twisting motion of the ventricles seen at magnetic resonance studies. Temporal Fourier analysis of equilibrium radionucleide angiocardiography, by studying the topography of the regional myocardial mechanical displacement corresponding to the wave front of electro-mechanical activation, provides information on the sequence of regional ventricular contraction was used in 29 normal individuals to observe the sequence of myocardial motion. Analysis disclosed that the base of the heart first moves (right then left ventricle) and mechanical movement later descends to involve the apex and the septum. These findings are in concordance with the proposed activation of the helical myocardium and open the way to more complex studies. Although electrical activation of the myocardium (QRS complex) follows a septum-apex-body-base of the left ventricle sequence, mechanical activation follows a base-to-apex sequence. This is likely to be related to anisotropic propagation of the electromechanical stimulus throughout the myocardial band once the electrical stimulus has been delivered at the base of the heart.

Spatial Light Modulators Based on Reflective Micro-Displays (Auf reflektiven Mikrodisplays basierende SMLs (Spatial Light Modulators))

Summary Spatial Light Modulator (SLM) systems for phase modulation of coherent light sources are mainly MEMS- (Micro-Electro-Mechanical Systems) or LCD- (Liquid Crystal Display) based. Driving forces for this technology are mainly the consumer electronics industry leading to high-resolution reflective micro-displays. These days panels with 1920 × 1200 pixel are available. The pixel pitch goes down to 8 microns, the devices can handle also high power applications and show an almost analogue modulation of the light either in amplitude or phase. The phase modulating properties of these devices enable a light efficient optical reconstruction of digital holographic data or active wave front control.

Method to predict isthmus location in ventricular tachycardia caused by reentry with a double-loop pattern

Method to Predict Isthmus Location. Background: During electrophysiologic study, induction and mapping of clinical reentrant ventricular tachycardia can be difficult. Hence, analysis of sinus-rhythm electrograms for reentry localization is of potential clinical relevance. Herein is described a method of sinus-rhythm electrogram shape analysis, that does not require arbitrary threshold values, for localization of double-loop reentrant circuits that drive clinical tachycardias. Methods and Results: Reentrant ventricular tachycardia was induced by premature stimulation in 23 postinfarction canine hearts 4-5 days after left anterior descending (LAD) ligation. Sinus-rhythm activation maps were constructed from bipolar electrograms acquired at 196-312 sites in the epicardial border zone. The timing of all electrogram peak deflections during one cycle of sinus rhythm was determined, and the mean (MPD) and deviation (DPD) were taken, respectively, as estimates of the time of activation wavefront crossing, and the duration of local electrical activity. These variables were then mapped on a computerized grid. The line of most uniform and sharp MPD gradient predicted the propagation direction through the double-loop reentrant circuit isthmus that would occur upon tachycardia induction. The sharpest transitions in DPD bounding this line predicted the positions of arcs of block that would border the reentrant circuit isthmus during tachycardia. The actual and estimated isthmuses overlapped by a mean of 84.1 ′ 3.8%. In six experiments lacking inducible reentrant tachycardia, no line of sharp MPD gradient was present in the MPD maps. Conclusions: Analysis of multiple sinus-rhythm deflections can localize the reentrant ventricular tachycardia isthmus without introduction of arbitrary threshold points and peak choices that may lead to error.

A Model of the Reflection of Activation Wavefronts in the Heart Ventricles of the Sheep onto the Epicardium and Body Surface

A Model of the Reflection of Activation Wavefronts in the Heart Ventricles of the Sheep onto the Epicardium and Body Surface

Runaway Pacemakers in Ventricular Fibrillation

Arunaway pacemaker is a malfunctioning pacemaker that paces the heart at rapid rates. A report from Australia 30 years ago1 described a patient with runaway pacemaker that paced the ventricles at 280 bpm. The patient survived only because one of the coauthors alertly cut the pacemaker wires to disconnect the high-frequency focal source from the myocardium. In this issue of Circulation , Thomas et al2 report that they occasionally detected sustained high-frequency sources during ventricular fibrillation (VF) in sheep with myocardial infarction (MI). Specifically, in 3 of 12 hearts, they detected periodic high-frequency activations at 1.3% of the intramural electrodes sampled. The authors propose that these findings support the hypothesis3 that a relatively stable periodic source (“mother rotor”), with fibrillatory conduction block occurring in the remainder of the ventricle, may be the mechanism of VF in this model. This mother rotor mechanism of fibrillation contrasts with the multiple wavelet mechanism, in which all rotors are unstable and wavebreak is the engine driving fibrillation. Both mechanisms of fibrillation have been documented in various settings,4 but controversy exists over which is the most common in and clinically relevant to diseased human hearts. This issue has therapeutic implications because it has been suggested that ablation of the mother rotor may be a strategy to abolish VF. At the same time, ablation of the mother rotor may just allow the next-fastest daughter rotor to take its place because fibrillatory wavebreaks act as niduses for new rotors. In any case, however, to even test this intriguing therapeutic strategy, it is first necessary to identify the location of the mother rotor, which has been elusive to date, especially in large animals.5 The findings of the present study, in a large-animal diseased heart model, are therefore significant. They also raise important questions. …

Ventricular Tachycardia Duration and Form Are Associated with Electrical Discontinuities Bounding the Core of the Reentrant Circuit

Successful prediction of reentrant ventricular tachycardia duration and form from sinus-rhythm electrogram signals in canine hearts is relevant to clinical studies, to potentially improve catheter ablation treatment during EP study. Following LAD ligation of canine hearts, activation maps were constructed from 312 border zone sites 4-5 days postinfarction. When reentrant ventricular tachycardia was inducible via programmed stimulation, the core of the circuit was defined on the maps as the enclosed area formed by the adjoining lines of slowest conduction and block bounding the protected region of the reentrant circuit. The number, location, and width of points of entrance or exit of the activation wavefront about the core were determined. Core perimeter location was then marked on the sinus-rhythm activation map, and the difference in activation time at opposite recording sites along the core perimeter was measured. Mean sinus-rhythm activation was highly discontinuous along the core perimeter in 10 transient reentry experiments (30.1 +/- 4.4 ms), moderately discontinuous in 13 sustained experiments (16.7 +/- 1.8 ms), and only slightly discontinuous in 5 noninducible experiments (9.7 +/- 1.7 ms). For transient versus sustained experiments, the entrance/exit points were narrower (mean: 6.5 +/- 1.0 mm vs 9.5 +/- 1.8 mm) with larger sinus-rhythm discontinuity across them (mean: 23.8 +/- 6.0 ms vs 11.8 +/- 2.1 ms). As core size increased, so did the number of entrance/exits present during reentry (P < 0.001). With increasing core size, four-loop (quatrefoil) reentry was frequently observed. Whether reentrant ventricular tachycardia will be inducible in the canine infarct border zone, and its duration and form, is associated with the characteristics of electrical discontinuities present about the core perimeter.

Method to Predict Isthmus Location in Ventricular Tachycardia Caused by Reentry with a Double‐Loop Pattern

During electrophysiologic study, induction and mapping of clinical reentrant ventricular tachycardia can be difficult. Hence, analysis of sinus-rhythm electrograms for reentry localization is of potential clinical relevance. Herein is described a method of sinus-rhythm electrogram shape analysis, that does not require arbitrary threshold values, for localization of double-loop reentrant circuits that drive clinical tachycardias. Reentrant ventricular tachycardia was induced by premature stimulation in 23 postinfarction canine hearts 4-5 days after left anterior descending (LAD) ligation. Sinus-rhythm activation maps were constructed from bipolar electrograms acquired at 196-312 sites in the epicardial border zone. The timing of all electrogram peak deflections during one cycle of sinus rhythm was determined, and the mean (MPD) and deviation (DPD) were taken, respectively, as estimates of the time of activation wavefront crossing, and the duration of local electrical activity. These variables were then mapped on a computerized grid. The line of most uniform and sharp MPD gradient predicted the propagation direction through the double-loop reentrant circuit isthmus that would occur upon tachycardia induction. The sharpest transitions in DPD bounding this line predicted the positions of arcs of block that would border the reentrant circuit isthmus during tachycardia. The actual and estimated isthmuses overlapped by a mean of 84.1 +/- 3.8%. In six experiments lacking inducible reentrant tachycardia, no line of sharp MPD gradient was present in the MPD maps. Analysis of multiple sinus-rhythm deflections can localize the reentrant ventricular tachycardia isthmus without introduction of arbitrary threshold points and peak choices that may lead to error.

Comparative effects of single- and linear triple-site rapid bipolar pacing on atrial activation in canine models

Nonuniform conduction may cause block and/or delay, thereby providing a substrate for the onset and maintenance of reentrant atrial arrhythmias. We tested the hypothesis that linear triple-site, bipolar, rapid pacing (LTSBRP) of the right atrium generates more uniform wave-front propagation compared with single-site, bipolar, rapid pacing (SSBRP), thereby reducing and/or eliminating conduction block and delay that is otherwise present. Five dogs with pericarditis and three normal dogs were studied. Three plunge-wire electrode pairs were placed 5-7 mm apart in both perpendicular and parallel configurations at the superior aspect of the crista terminalis and were used to pace at 200- and 300-ms cycle lengths for < or =6 s. During pacing, 380 electrograms were recorded simultaneously from electrode arrays placed epicardially on the atria, which produced activation sequence maps for each pacing episode. Local conduction-velocity vectors were computed for each site during each episode. Histograms of absolute velocity vector angles from the x-axis (of the crista terminalis) were plotted to assess uniformity of wave-front propagation, and the magnitude of each vector was computed to assess the local speed. LTSBRP showed 1) more uniform linear activation wave fronts compared with SSBRP, 2) velocity vectors with a more uniform magnitude and direction compared with SSBRP, 3) a predominant absolute velocity vector angle vs. a scattered angle distribution with SSBRP, and 4) shorter right atrial activation time and faster mean epicardial speed than SSBRP for each pacing cycle length. LTSBRP created a more uniform wave-front propagation with less or no conduction block and/or delay compared with SSBRP.

100-kHz diffraction-limited femtosecond laser micromachining

We demonstrate active and adaptive wavefront correction of a 100-kHz amplified femtosecond laser chain, and investigate the subsequent improvement for micromachining applications. Thanks to a non-pixelated liquid-crystal modulator, phase-front distortions are decreased down to λ/15 peak–valley and λ/100 rms. Clean 1.7-μm diffraction-limited microholes are obtained, both on low-threshold metallic and high-threshold dielectric materials. This high beam quality femtosecond source enables diffraction-limited high-speed micromachining.

The fine-scale architecture of defibrillation

See article by Sharifov et al. (pages 448–456) in this issue Ventricular fibrillation is fatal, unless it self-terminates or is terminated by an intervention. It probably is partially responsible for most non-violent deaths and is the immediate cause of death in most sudden cardiac deaths, which form up to a fifth of adult premature deaths in the developed world [1]. The only effective treatment is prompt defibrillation by a brief, large-amplitude electrical shock that produces a field of more than 5 V/cm in the myocardium. Since DC cardiac defibrillation/cardioversion was pioneered by Lown [2] in the 1960s, there have been substantial improvements in the engineering of defibrillators, leading to implantable devices for high-risk patients and public access automatic defibrillators in public areas [1,3]. However, the cellular and tissue electrophysiological mechanisms that underlie defibrillation remain poorly understood and controversial. Improvement in the spatial resolution of optical recording of the spatio-temporal pattern of activity across the ventricular wall produced by electrical shocks has helped to clarify these mechanisms. Fibrillation is produced by irregular, self-sustained propagation of activation wave fronts through the ventricle. The wave front will propagate into tissue that has recovered its excitability (the excitable gap), with a velocity that depends on both its local curvature and the relative refractoriness of the tissue (determined by the time since the previous activation, or the rate of activity). During normal sinus rhythm, the ventricular activation wave front forms a continuous surface, propagating from the sub-endocardial Purkinje fibers towards the epicardium. At a line break in the activation surface, produced by some heterogeneity, propagation may curl back on itself and … *Tel.: +44 113 343 4251; fax: +44 113 343 4230. Email address: arun{at}cbiol.leeds.ac.uk

A Theoretical Model of the High-Frequency Arrhythmogenic Depolarization Signal Following Myocardial Infarction

Theoretical body-surface potentials were computed from single, branching and tortuous strands of Luo-Rudy dynamic model cells, representing different areas of an infarct scar. When action potential (AP) propagation either in longitudinal or transverse direction was slow (3-12 cm/s), the depolarization signals contained high-frequency (100-300 Hz) oscillations. The frequencies were related to macroscopic propagation velocity and strand architecture by simple formulas. Next, we extended a mathematical model of the QRS-complex presented in our earlier work to simulate unstable activation wavefront. It combines signals from different strands with small timing fluctuations relative to a large repetitive QRS-like waveform and can account for dynamic changes of real arrhythmogenic micropotentials. Variance spectrum of wavelet coefficients calculated from the composite QRS-complex contained the high frequencies of the individual abnormal signals. We conclude that slow AP propagation through fibrotic regions after myocardial infarction is a source of high-frequency arrhythmogenic components that increase beat-to-beat variability of the QRS, and wavelet variance parameters can be used for ventricular tachycardia risk assessment.

Does cardiac pacing reproduce the mechanism of focal impulse initiation?

Stimulation of myocardium by either a native pacemaker or an artificial stimulus requires the initiation of a self-propagating wave of depolarization originating from the site of initial activation. In the present study we perform artificial stimulation at a site of focal discharge with the aim to compare the two mechanisms of impulse formation. High resolution epicardial mapping in senescent rat hearts provided examples of focal discharge during sinus rhythm at a single epicardial breakthrough (BKT) point emerging from an isolated Purkinje-ventricular muscle junction (PMJ) site. Stimulation was also performed at the same BKT point and potential distributions recorded during spontaneous and artificial stimulation were compared. During excitation latency, the negative potential pattern was elongated perpendicularly to fiber direction at both pacing and BKT point, in agreement with virtual cathode membrane polarization predicted by the bidomain model during point stimulation. During impulse initiation, activation wave fronts were initially circular around pacing site or BKT point and then elongated along local fiber direction. The similarity between impulse initiation during focal discharge and point stimulation in cardiac muscle suggests that high resolution pace mapping studies can help to elucidate the mechanism of abnormal impulse formation.

Non-contact mapping to guide radiofrequency ablation of atypical right atrial flutter

This study was aimed at evaluating the efficacy of non-contact mapping and ablation of non-incisional atypical right atrial (RA) flutters. The majority of atypical RA flutters were reported in patients after surgical incision of the RA. The study group consisted of 15 patients (61 +/- 13 years, 8 males) with atypical atrial flutter (AFL). The RA activation during AFL was delineated using a non-contact mapping system (EnSite 3000 with Precision Software, Endocardial Solutions, St. Paul, Minnesota). The narrowest part of each reentrant circuit was targeted using radiofrequency energy. In all 15 patients, non-contact mapping showed AFLs confined to the RA with RA activation time accounting for 100% of the cycle length (210 +/- 19 ms). During single-loop re-entry in seven patients, the activation wave front circulated around the central obstacle (CO) in the anterolateral wall with conduction through the channel between the CO and the crista terminalis (CT). During figure-of-eight re-entry in eight patients, simultaneous upper and lower loop re-entry through the conduction gap in the CT was found in four patients, and simultaneous upper loop and free-wall single-loop re-entry was observed in four patients. Radiofrequency ablation of the free-wall channel and/or CT gap was effective in eliminating these AFLs in 13 patients. During a follow-up of 16.8 +/- 3.8 months, two patients had recurrence of left AFL, and one had recurrence of atrial fibrillation. Atypical RA flutters could arise from single-loop or double-loop figure-of-eight re-entry. Radiofrequency ablation of the free-wall channel and/or the CT gap was effective in eliminating these arrhythmias.

The spectrum of inter- and intraventricular conduction abnormalities in patients eligible for cardiac resynchronization therapy.

Although cardiac resynchronization therapy (CRT) has clearly demonstrated its clinical benefit in patients with congestive heart failure (CHF) and intraventricular conduction abnormalities, selection of eligible patients and/or optimal pacing site are still a matter of debate. The aim of the study was to analyze the spectrum of conduction abnormalities in CRT candidates. A total of 26 patients (mean age 62 +/- 9 years) with CHF and conduction disturbances (QRS > or = 130 ms) were studied. The underlying heart disease was dilated cardiomyopathy (DCM) (n = 12) or coronary artery disease (CAD) (n = 14). High density, left ventricular endocardial activation maps were constructed using an electroanatomic mapping system (CARTO). Based on endocardial activation patterns, left ventricular conduction abnormalities were classified as left bundle branch block (LBBB) (n = 9), nonspecific intraventricular conduction disturbances (n = 10), and the bifascicular block (n = 7). In DCM patients the endocardial activation sequences corresponded with a 12-lead ECG pattern with a homogeneous spread of activation wavefront and the latest activation laterally (LBBB) or anteriorly (bifascicular block), respectively. CAD patients presented with variable activation patterns that reflected the location of the postinfarct scar, and the 12-lead ECG was less predictive. Although there was a trend for longer QRS durations for DCM subjects (170 +/- 23 vs 156 +/- 23 ms, P = NS), left ventricular activation time was significantly longer in the CAD group (115 +/- 21 ms vs 134 +/- 23 ms, P < 0.05). CRT candidates represent a broad spectrum of conduction abnormality patterns with variable inter- and intraventricular activation delays. CAD subjects have more pronounced intraventricular conduction abnormality. The standard ECG is less reliable in the characterization of complex conduction abnormalities.

Role of gap junctions in the propagation of the cardiac action potential.

Gap junctions play a pivotal role for the velocity and the safety of impulse propagation in cardiac tissue. Under physiologic conditions, the specific subcellular distribution of gap junctions together with the tight packaging of the rod-shaped cardiomyocytes underlies anisotropic conduction, which is continuous at the macroscopic scale. However, when breaking down the three-dimensional network of cells into linear single cell chains, gap junctions can be shown to limit axial current flow and to induce 'saltatory' conduction at unchanged overall conduction velocities. In two- and three-dimensional tissue, these discontinuities disappear due to lateral averaging of depolarizing current flow at the activation wavefront. During gap junctional uncoupling, discontinuities reappear and are accompanied by slowed and meandering conduction. Critical gap junctional uncoupling reduces conduction velocities to a much larger extent than does a reduction of excitability, which suggests that the safety for conduction is higher at any given conduction velocity for gap junctional uncoupling. In uniformly structured tissue, gap junctional uncoupling is accompanied by a parallel decrease in conduction velocity. However, this is not necessarily the case for non-uniform structures like tissue expansion where partial uncoupling paradoxically increases conduction velocity and has the capacity to remove unidirectional conduction blocks. Whereas the impact of gap junctions on impulse conduction is generally assessed from the point of view of cell coupling among cardiomyocytes, it is possible that other cell types within the myocardium might be coupled to cardiomyocytes as well. In this context, it has been shown that fibroblasts establish successful conduction between sheets of cardiomyocytes over distances as long as 300 microm. This might not only explain electrical synchronization of heart transplants but might be of importance for cardiac diseases involving fibrosis. Finally, the intriguing fact that sodium channels are clustered at the intercalated disc recently rekindled the provocative question of whether gap junctions alone are responsible for impulse propagation or whether electric field mechanisms might account for conduction as well. Whereas computer simulations show the feasibility of conduction in the absence of gap junctional coupling, a definite answer to this question must await further investigations into the biophysical properties of the intercalated disc.