Reentrant Wave Front Research Articles

Effects of procainamide on wave-front dynamics during ventricular fibrillation in open-chest dogs.

There is increasing evidence that both functional reentrant wave fronts and multiple wavelets are present during ventricular fibrillation (VF). However, the effects of procainamide on the characteristics of activation waves during VF are poorly understood. Seven dogs were studied; six underwent subendocardial chemical ablation procedures. A plaque with 317 to 480 bipolar electrodes was sutured to the right ventricular free wall, and the patterns of activation were registered with a computerized mapping system. VF was electrically induced, and the patterns of activation were registered at baseline and during procainamide infusion (serum concentration, 9.3+/-1.9 microg/mL). Among the six dogs that had their subendocardium ablated, reentrant wave fronts were present in 6 of the 108 runs of VF at baseline and in 6 of the 100 runs of VF during procainamide infusion. By analyzing the wave fronts, we found that the cycle length, refractory period, conduction velocity, and wavelength at baseline were 101+/-9 ms, 54+/-5 ms, 0.93+/-0.21 mm/ms, and 51+/-16 mm, respectively, and during procainamide infusion, values became 125+/-11 ms (P<.001), 119+/-7 ms (P<.001), 0.42+/-0.02 mm/ms (P<.001), and 50+/-4 mm (P=.8), respectively. The vast majority of the activation waves do not form organized reentry. These activation waves broke up more frequently at baseline than during procainamide administration. The number of activation waves was 7.25+/-1.39 s(-1) x cm(-2) at baseline and 4.45+/-1.80 s(-1) x cm(-2) during procainamide administration (P<.001). The dog without subendocardial ablation had similar results. Procainamide decreases the number of wavelets during VF by preventing spontaneous wave breaks. This represents a novel mechanism of antiarrhythmic drug action.

Computerized mapping of fibrillation in normal ventricular myocardium.

It is well known that the ability to fibrillate is intrinsic to a normal ventricle that exceeds a critical mass. The questions we address are how is ventricular fibrillation (VF) initiated and perpetuated in normal myocardium, and why is VF not seen more often in the general population if all ventricles have the ability to fibrillate. To study the mechanisms of VF, we used computerized mapping techniques with up to 512 channels of simultaneous multisite recordings for data acquisition. The data were then processed for dynamic display of the activation patterns and for mathematical analyses of the activation intervals. The results show that in normal ventricles, VF can be initiated by a single strong premature stimulus given during the vulnerable period of the cardiac cycle. The initial activations form a figure-eight pattern. Afterward, VF will perpetuate itself without any outside help. The self-perpetuation itself is due to at least two factors. One is that single wave fronts spontaneously break up into two or more wavelets. The second is that when two wavelets intersect perpendicular to each other, the second wavelet is broken by the residual refractoriness left over from the first wavelet. Mathematical analyses of the patterns of activation during VF revealed that VF is a form of chaos, and that transition from ventricular tachycardia (VT) to VF occurs via the quasiperiodic route. In separate experiments, we found that we can convert VF to VT by tissue size reduction. The physiological mechanism associated with the latter transition appears to be the reduction of the number of reentrant wave fronts and wandering wavelets. Based on these findings, we propose that the reentrant wave fronts and the wandering wavelets serve as the physiological equivalent of coupled oscillators. A minimal number of oscillators is needed for VF to perpetuate itself, and to generate chaotic dynamics; hence a critical mass is required to perpetuate VF. We conclude that VF in normal myocardium is a form of reentrant cardiac arrhythmia. A strong electrical stimulus initiates single or dual reentrant wave fronts that break up into multiple wavelets. Sometimes short-lived reentry is also generated during the course of VF. These organized reentrant and broken wavelets serve as coupled oscillators that perpetuate VF and maintain chaos. Although the ability to support these oscillators exists in a normal ventricle, the triggers required to generate them are nonexistent in the normal heart. Therefore, VF and sudden death do not happen to most people with normal ventricular myocardium. (c) 1998 American Institute of Physics.

Characteristics of the Temporal and Spatial Excitable Gap in Anisotropic Reentrant Circuits Causing Sustained Ventricular Tachycardia

The excitable gap of a reentrant circuit has both temporal (time during the cycle length that the circuit is excitable) and spatial (length of the circuit that is excitable at a given time) properties. We determined the temporal and spatial properties of the excitable gap in reentrant circuits caused by nonuniform anisotropy. Myocardial infarction was produced in canine hearts by ligation of the left anterior descending coronary artery. Four days later, reentrant circuits were mapped in the epicardial border zone of the infarcts with a multielectrode array during sustained ventricular tachycardia induced by programmed stimulation. During tachycardia, premature impulses were initiated by stimulation at sites around and in the reentrant circuits, and their conduction characteristics in the circuit were mapped. All circuits had a temporal excitable gap in at least part of the circuit, which allowed premature impulses to enter the circuit. Completely and partially excitable segments of the temporal gap were identified by measuring conduction velocity of the premature impulses; conduction was equal to the native reentrant wave front in completely excitable regions and slower than the reentrant wave front in partially excitable regions. In some circuits, a temporal gap existed throughout the circuit, permitting the entire circuit to be reset over a range of premature coupling intervals, although the size of the gap varied at different sites. In other circuits, the gap became so small at local sites that even though premature impulses could enter the circuit, the circuit could not be reset. Premature impulses could terminate reentry in circuits that could be reset or not. We also found a significant spatial gap, which was identified by determining the distance between the head of the circulating wave front, which could be located on the activation map, and its tail, which was the site most distal from the head as located by the site of entry of the premature wave front into the circuit. The spatial gap could also vary in different parts of the circuit. Therefore, nonuniform anisotropic reentrant circuits have both a temporal and spatial excitable gap with fully and partially excitable components that change in different parts of the circuit.

Mechanisms for Spontaneous Termination of Monomorphic, Sustained Ventricular Tachycardia: Results of Activation Mapping of Reentrant Circuits in the Epicardial Border Zone of Subacute Canine Infarcts

Objectives. The objective of this study was to determine why sustained ventricular tachycardias (VT) sometimes stop without outside intervention.Background. Sustained, monomorphic VT in patients with ischemic heart disease is often caused by reentrant excitation. These tachycardias can degenerate into rapid polymorphic rhythms or occasionally terminate spontaneously.Methods. Sustained VT was induced by programmed stimulation in dog hearts 4 to 5 days after ligation of the left anterior descending coronary artery. Activation in reentrant circuits in the epicardial border zone of the infarct was mapped using 192 to 312 bipolar electrodes.Results. Spontaneous termination of sustained VT always occurred when the reentrant wave front blocked in the central common pathway in reentrant circuits with a figure-of-eight configuration. Two major patterns of termination were identified from activation maps of the circuits that were not distinguishable from each other on the surface electrocardiogram: 1) Abrupt termination was not preceded by any change in the pattern of activation or cycle length. It could occur at different locations within the central common pathway, was not related to the directions of the muscle fiber orientation and was not caused by a short excitable gap. 2) Termination caused by premature activation (after a short cycle) either resulted from shortening of the functional lines of block around which the reentrant impulse circulated or was caused by wave fronts originating outside the reentrant circuit. In only one episode were oscillations of cycle length associated with termination.Conclusions. The mechanisms for termination of reentry in functional circuits causing VT are different from those in anatomic circuits where oscillatory behavior precedes termination.

Mechanisms causing sustained ventricular tachycardia with multiple QRS morphologies: results of mapping studies in the infarcted canine heart.

Sustained reentrant ventricular tachycardias (VTs) with different QRS morphologies have been observed to occur spontaneously and during programmed stimulation in human hearts. We determined mechanisms that can cause tachycardias with multiple morphologies in a canine model of myocardial infarction by mapping reentrant circuits. Reentrant VT with multiple QRS morphologies was induced in 11 canine hearts with 4-day-old infarcts. Comparison of activation maps of the reentrant circuits in the epicardial border zone associated with each morphology indicated two basic mechanisms. Less frequently, VTs of different morphologies in the same heart were caused by reentrant circuits in different regions of the infarct. Most commonly, the reentrant circuits associated with different morphologies were in the same region. Three different factors caused different exit routes from circuits in the same region, leading to the multiple morphologies. (1) The reentrant wave front for each morphology rotated around the same line of block but in different directions. (2) Reentrant circuits associated with each morphology were similar, but there were small changes in the extent of the central line of block. (3) Reentrant circuits with completely different sizes and shapes caused different morphologies. In this canine model, tachycardias with multiple morphologies most commonly arise from reentrant circuits in the same region of the infarct, suggesting that most often only one area has electrophysiological properties necessary to sustain reentry.

Spatiotemporal complexity of ventricular fibrillation revealed by tissue mass reduction in isolated swine right ventricle. Further evidence for the quasiperiodic route to chaos hypothesis.

We have presented evidence that ventricular fibrillation is deterministic chaos arising from quasiperiodicity. The purpose of this study was to determine whether the transition from chaos (ventricular fibrillation, VF) to periodicity (ventricular tachycardia) through quasiperiodicity could be produced by the progressive reduction of tissue mass. In isolated and perfused swine right ventricular free wall, recording of single cell transmembrane potentials and simultaneous mapping (477 bipolar electrodes, 1.6 mm resolution) were performed. The tissue mass was then progressively reduced by sequential cutting. All isolated tissues fibrillated spontaneously. The critical mass to sustain VF was 19.9 +/- 4.2 g. As tissue mass was decreased, the number of wave fronts decreased, the life-span of reentrant wave fronts increased, and the cycle length, the diastolic interval, and the duration of action potential lengthened. There was a parallel decrease in the dynamical complexity of VF as measured by Kolmogorov entropy and Poincaré plots. A period of quasiperiodicity became more evident before the conversion from VF (chaos) to a more regular arrhythmia (periodicity). In conclusion, a decrease in the number of wave fronts in ventricular fibrillation by tissue mass reduction causes a transition from chaotic to periodic dynamics via the quasiperiodic route.

Induction of meandering functional reentrant wave front in isolated human atrial tissues.

The purpose of this study was to test the hypothesis that a single meandering functional reentrant wave front can result in rapid and irregular electrogram activity in human atrial tissues. The study used the explanted hearts of five human cardiac transplant recipients. Three right and two left atrial tissue samples, 3.4+/-0.3 mm thick, were excised and trimmed to 3.5x3.0 cm. The isolated atrium was placed endocardial surface down in a chamber with a 477 bipolar recording electrode array built into the bottom of the tissue bath. The interelectrode distance was 1.6 mm. The tissue was constantly superfused with 36.5 degrees C oxygenated Tyrode's solution at a rate of 10 mL/min. After eight baseline stimuli (S1) delivered at 400- or 600-ms cycle length from the edge of the tissue, a single premature stimulus (S2) was given at the center of the tissue to induce reentry. A total of nine episodes of reentry were induced with S1-S2 coupling intervals of 232+/-29 ms (range, 190 to 290 ms) and an S2 strength of 10+/-3 mA (range, 5 to 15 mA). In all samples, a single meandering reentrant wave front was induced, causing irregular and rapid bipolar electrogram activity. These wave fronts had a mean cycle length of 229+/-45 ms (160 to 290 ms) and persisted for 1.1+/-0.3 seconds (0.6 seconds to 2.5 seconds), or 5.2+/-1.4 (3 to 9) cycles, before spontaneous termination. A single meandering functional reentrant wave front can be induced in human atrial tissues and produce rapid and irregular electrical activity.

Attachment of meandering reentrant wave fronts to anatomic obstacles in the atrium. Role of the obstacle size.

Acetylcholine chloride (ACh) induces nonstationary meandering reentrant wave fronts in the atrium. We hypothesized that an anatomic obstacle of a suitable size prevents meandering by causing attachment of the reentrant wave front tip to the obstacle. Eight isolated canine right atrial tissues (area, 3.8 x 3.2 cm) were mounted in a tissue bath and superfused with Tyrode's solution containing 10 to 15 mumol/L ACh. Holes with 2- to 10-mm diameters were sequentially created in the center of the tissue with biopsy punches. Reentry was induced by a premature stimulus after eight regular stimuli at 400-ms cycle length. The endocardial activation maps and the motion of the induced reentry were visualized dynamically before and after each test lesion using 509 bipolar electrodes. In the absence of a lesion (n = 8), the induced single reentrant wave front, in the form of a spiral wave, meandered irregularly from one site to another before terminating at the tissue border. Holes with 2- to 4-mm diameters (n = 6) had no effect on meandering. However, when the hole diameters were increased to 6 mm (n = 8), 8 mm (n = 8), and 10 mm (n = 6), the tip of the spiral wave attached to the holes, and reentry became stationary. Transition from meandering to an attached state converted the irregular and polymorphic electrogram to a periodic and monomorphic activity with longer cycle lengths (101 +/- 11 versus 131 +/- 9 ms for no hole versus 10-mm hole, respectively; P < .001). Regression analysis showed a significant positive linear correlation between the cycle length of the reentry and the hole diameter (r = .89, P < .01) and between the cycle length of the reentry and the excitable gap (r = .89, P < .05). We conclude that a critically sized anatomic obstacle converts a nonstationary meandering reentrant wave front to a stationary one. This transition converts an irregular "fibrillation-like" activity into regular monomorphic activity.

Meandering and unstable reentrant wave fronts induced by acetylcholine in isolated canine right atrium.

The mechanism(s) by which acetylcholine (ACh) increases atrial vulnerability to reentry and maintains its activity for longer durations remains poorly defined. In the present study we used high-resolution activation maps to test the hypothesis that ACh promotes meandering of atrial reentrant wave fronts, resulting in breakup and the generation of new wave fronts that sustain the activity. Reentry was induced in 11 isolated canine right atrial tissues (3.8 x 3.2 cm) by a premature point stimulus (S2) before and after superfusion with ACh (15 x 10(-6) M). Endocardial isochronal activation maps were constructed with the use of 509 bipolar electrodes (1.6-mm spatial resolution), and the dynamics of the activation wave fronts were visualized with animation. A vulnerable period was found during which an S2 current strength > 4.4 +/- 2.5 mA [lower limit of vulnerability (LLV)] and < 26 +/- 13 mA [upper limit of vulnerability (ULV)] induced a single stationary reentrant wave front that lasted 3 +/- 2.5 s with a period of 159 +/- 17 ms (16 episodes). AC shortened the refractory period from 100 +/- 12 to 59 +/- 9 ms (P < 0.001) and increased vulnerability to reentry induction by simultaneous decrease in the LLV (0.7 +/- 0.2 mA, P < 0.001) and an increase in the ULV (82 +/- 24 mA, P < 0.01). ACh accelerated the rate (period of 110 +/- 16 ms, P < 0.001) and converted the stationary reentrant wave front to a nonstationary (meandering) reentrant wave front showing polymorphic electrograms, i.e., "fibrillation-like" activity (22 episodes). Rapid meandering of the reentry tip led to wave front breakup (18 episodes) and the generation of new wave fronts (19 episodes). These wave front dynamics also led to sustained (76 +/- 224 s, P < 0.001) fibrillation-like electrograms. We conclude that ACh increases the ULV and promotes meandering of a single reentrant wave front, leading to breakup and the generation of new wave fronts. Single meandering and complex wave front dynamics cause fibrillation-like activity and sustain the activity for longer duration.

Spirals, chaos, and new mechanisms of wave propagation.

The chaos theory is based on the idea that phenomena that appear disordered and random may actually be produced by relatively simple deterministic mechanisms. The disordered (aperiodic) activation that characterizes a chaotic motion is reached through one of a few well-defined paths that are characteristic of nonlinear dynamical systems. Our group has been studying VF using computerized mapping techniques. We found that in electrically induced VF, reentrant wavefronts (spiral waves) are present both in the initial tachysystolic stage (resembling VT) and the later tremulous incoordination stage (true VF). The electrophysiological characteristics associated with the transition from VT to VF is compatible with the quasiperiodic route to chaos as described in the Ruelle-Takens theorem. We propose that specific restitution of action potential duration (APD) and conduction velocity properties can cause a spiral wave (the primary oscillator) to develop additional oscillatory modes that lead to spiral meander and breakup. When spiral waves begin to meander and are modulated by other oscillatory processes, the periodic activity is replaced by unstable quasiperiodic oscillation, which then undergoes transition to chaos, signaling the onset of VF. We conclude that VF is a form of deterministic chaos. The development of VF is compatible with quasiperiodic transition to chaos. These results indicate that both the prediction and the control of fibrillation are possible based on the chaos theory and with the advent of chaos control algorithms.

Simultaneous multisite mapping studies during induced atrial fibrillation in the sterile pericarditis model. Insights into the mechanism of its maintenance.

Chronic atrial fibrillation (AF) is thought to be due to multiple, simultaneously circulating wavelets. In the canine sterile pericarditis model, the mechanisms of maintenance of AF are not yet understood. During six induced AF episodes in six dogs with sterile pericarditis, 372 unipolar electrograms were recorded simultaneously from an electrode array placed around both atrial free walls, along with 10 to 24 electrodes from the atrial septum, by use of a multiplexing system. Activation maps during 12 consecutive 100-ms windows were analyzed from an episode of sustained AF in each dog (mean duration, 32 +/- 24 minutes). In two dogs, two such activation maps during the same episode of AF were analyzed. During AF, multiple unstable reentrant circuits (mean number, 1.4 +/- 0.1 per 100-ms analysis window) with very short cycle lengths (mean, 111 +/- 8 ms) present primarily in the atrial septum and right atrium were responsible for maintenance of AF. The unstable reentrant circuits frequently disappeared and re-formed. Wave fronts traveling from one atrium to the other and/or from the atrial septum play an important role in re-formation of unstable reentrant wave fronts. In this model of paroxysmal AF, unstable reentrant circuits of very short cycle length principally involving the atrial septum appear to be critical for maintenance of AF. Some reentrant circuits disappear as others re-form, so that at least one reentrant circuit is always present. Because the atria cannot follow their very short cycle lengths in a 1:1 manner, AF is maintained.

Mechanism of spontaneous termination of functional reentry in isolated canine right atrium. Evidence for the presence of an excitable but nonexcited core.

According to the spiral wave hypothesis of reentry, the core of functional reentry remains excitable but not excited. We sought to determine whether the core remains excitable and whether excitation of the core by an outside wave front leads to termination of the reentry in the atrium. In nine isolated canine right endocardial atrial tissues (3.8 by 3.2 cm wide), reentry was induced by a premature point stimulus (S2). The isochronal activation maps and dynamics of the activation patterns were visualized with the use of 509 bipolar electrodes (1.6-mm resolution). The S2 applied after 8 regular beats induced reentry with a mean cycle length of 162 +/- 20 ms (15 episodes). Reentry had a large excitable gap (93 +/- 26 ms) as determined by early capture with twice the level of threshold stimuli. The central area (core) around which the wave fronts rotated had a mean surface area of 12 +/- 3 mm2. The electrograms located in the core of the reentry registered no or very low amplitude potentials. In 13 of 15 episodes, reentry terminated when an outside new wave front merged with the original wave front and excited the core. Core excitation caused disruption of the original wave front, and the newly formed wave front(s) vanished at the tissue border within 77 +/- 18 ms. In 2 episodes, reentry terminated abruptly when an outside new wave front propagating in a direction opposite to the reentrant wave front collided with the leading edge of the reentrant wave front. Functional reentry in the atrium is compatible with a spiral wave of excitation with an excitable but nonexcited core and a large excitable gap. Reentry may be terminated either by direct excitation of the core that displaces the wave front to the tissue border or by collision with an outside new wave front.

Characterization and surgical ablation of atrial flutter after the classic fontan repair

Atrial flutter (AFL) is a frequent postoperative complication of the classic Fontan operation, which uses an atriopulmonary connection. We hypothesized that the suture lines alone, in the absence of any hemodynamic alterations, provide the necessary electrophysiologic substrates for AFL. The objectives of this study were to determine if the Fontan suture lines alone are sufficient to permit sustained AFL in an acute canine model and to characterize any resulting reentrant circuits to surgically ablate the AFL. After cardiopulmonary bypass, adult dogs (n = 18) underwent a simulated classic Fontan operation. This included a longitudinal right atriotomy and an incision from the base of the right atrial appendage toward the dome of the left atrium, representing the atriopulmonary connection. In 6 of 18 dogs, an atrial septal defect was created at the level of the fossa ovalis. Unipolar 253-point biatrial endocardial mapping electrodes were placed via bilateral ventriculotomies. Induction of AFL was attempted by atrial burst pacing. If AFL could not be induced, isoproterenol was administered and pacing repeated. Activation sequence maps of the pathways of atrial reentry were generated. In 8 dogs with inducible AFL, an incision was made from the atriotomy to the atriopulmonary connection and burst pacing repeated. Sustained AFL could not be induced after bypass alone in any case. After the simulated Fontan operation, sustained AFL was reproducibly induced in all 18 dogs, 6 of which required isoproterenol. The mean cycle length of all cases was 177 +/- 20 ms. During AFL, atrial activation sequence maps demonstrated lines of conduction block created by both the atriotomy and the atriopulmonary connection. The isthmus of tissue between these two lines of block was essential for propagation of the reentrant wavefront. Interruption of this isthmus with an incision successfully terminated AFL in 8 of 8 dogs. In an acute canine model, the Fontan suture lines alone, in the absence of atrial hypertension or stretch, permit the induction of AFL. An essential electrophysiologic substrate is an isthmus of myocardium between the atriotomy and the atriopulmonary connection. Interruption of conduction through this isthmus terminates the AFL in this model and suggests a technique for ablation of AFL in patients who have undergone a classic Fontan operation.

Lateral tunnel suture line variation reduces atrial flutter after the modified Fontan operation

Atrial flutter (AFL) is a common postoperative sequela of the modified Fontan operation, or total cavopulmonary connection. We hypothesized that injury to the crista terminalis (CT) by the lateral tunnel suture line contributes to the development of AFL in this setting. This study was designed to determine the effects of alteration of the lateral tunnel suture line, relative to the CT, on the inducibility of AFL in an acute canine model of the modified Fontan operation. Adult mongrel dogs (n = 25) underwent a median sternotomy and normothermic cardiopulmonary bypass. In groups 1, 2, and 3, through a right atriotomy, a suture line was placed to simulate the lateral tunnel of the modified Fontan operation (n = 20). The lateral aspect of the suture line ran along the CT in group (n = 10), 5 mm medial to the CT in group 2 (n = 5), and 10 mm anterior to the CT, incorporated into the atriotomy closure, in group 3 (n = 5). In group 4 (n = 5), only the lateral portion of the suture line, along the CT, was placed. Form-fitting 253-point unipolar endocardial mapping electrodes were inserted in the left and right atria via bilateral ventriculotomies. Induction of AFL was then attempted using atrial burst pacing. If sustained AFL could not be induced, isoproterenol was administered and the pacing protocol repeated. Endocardial activation sequence maps of spontaneous rhythm and AFT were constructed. Under baseline conditions, after placement of the suture line, sustained AFL could reproducibly be induced in 8/10 dogs in group 1, 0/5 dogs in group 2, 0/5 dogs in group 3, and 5/5 dogs in group 4 (p < 0.001). After isoproterenol administration, sustained AFL was reproducibly inducible in the remaining 2 dogs in group 1, 4/5 dogs in group 2, and 0/5 dogs in group 3 (p = 0.01). The mean cycle length of AFL was 189 +/- 25 ms in group 1, 136 +/- 8 ms in group 2, and 182 +/- 20 ms in group 4 (p < 0.001). Atrial activation sequence maps, during sinus rhythm, demonstrated a line of conduction block along the lateral portion of the suture line in all cases in groups 1 and 4 and in only those cases in group 2 in which sustained AFL was inducible. During AFL this block facilitated unidirectional conduction, permitting propagation of the reentrant wavefront. Mean conduction velocity along the CT during sinus rhythm was 0.63 +/- 0.10 m/s in group 1, 1.04 +/- 0.17 m/s in group 2, 1.01 +/- 0.12 m/s in group 3, and 0.44 +/- 0.13 m/s in group 4 (p < 0.01). In an acute canine model of the modified Fontan operation, conduction block imposed by the lateral tunnel suture line is an essential component of the AFL circuit. The inducibility of AFL is increased by suture line placement along the CT. Slow conduction, resulting from injury to the CT, promotes this increased inducibility. Avoidance of the CT may reduce the incidence of AFL in children undergoing the modified Fontan operation.

Reentrant wave fronts in Wiggers' stage II ventricular fibrillation. Characteristics and mechanisms of termination and spontaneous regeneration.

The mechanisms of Wiggers' stage II ventricular fibrillation (VF) are poorly understood. Using computerized mapping techniques, we studied the patterns of activation during Wiggers' stage II VF in 13 open-chest dogs. In 7 of the 13 dogs, the right ventricular Purkinje fibers and adjacent subendocardial myocytes were ablated with Lugol solution. VF was induced electrically, and 3 to 5 seconds of data were obtained beginning approximately 2.5 seconds after the onset of VF. Dynamic displays of the activation patterns and isochronal maps revealed the presence of reentrant wave fronts in 17 of 33 runs of VF in ablated ventricles and in 12 of 45 runs of VF in intact ventricles. The incidence of reentry was not different between the subendocardium-ablated group versus the nonablated group (1.7 +/- 1.6 versus 1.2 +/- 1.6 rotations per episode of VF, P = .19). There were no differences in the core size (25 +/- 19 versus 29 +/- 18 mm2), life span (3.4 +/- 1.1 versus 3.2 +/- 1.2 rotations), or cycle length (111 +/- 12 versus 107 +/- 8 ms) in ablated ventricles versus intact ventricles, respectively. The core was unstable as it meandered within the mapped area displacing the entire reentrant wave front. In all episodes, the reentrant wave fronts were spontaneously initiated by an interaction between two propagating wave fronts roughly perpendicular to each other. The second wave front met the tail of the first wave front 69 +/- 11 ms (range, 40 to 90 ms) after its latest activation, indicating that the interaction occurred during a vulnerable period. The reentrant wave fronts terminated spontaneously (n = 7), as the result of interference by an invading wave front (n = 19 or meandered off the mapped region (n = 3). We conclude the following: (1) Reentrant activities with short life spans and meandering cores are present during Wiggers' stage II VF in dogs. (2) New reentrant wave fronts are generated when one wave front interacts with another wave front during its vulnerable period. (3) The reentrant wave fronts terminate spontaneously or as the result of interference. (4) Chemical subendocardial ablation does not affect the incidence, life span, cycle length, or core size of the reentrant wave fronts.

Conversion of non-stationary to stationary reentrant wave front with a critically-sized anatomical obstacle in the atrium

Conversion of non-stationary to stationary reentrant wave front with a critically-sized anatomical obstacle in the atrium

Mechanisms of termination of reentrant wave fronts in the atrium: Implications for prevention of atrial fibrillation

Mechanisms of termination of reentrant wave fronts in the atrium: Implications for prevention of atrial fibrillation

Proarrhythmic response to potassium channel blockade. Numerical studies of polymorphic tachyarrhythmias.

Prompted by the results of CAST results, attention has shifted from class I agents that primarily block sodium channels to class III agents that primarily block potassium channels for pharmacological management of certain cardiac arrhythmias. Recent studies demonstrated that sodium channel blockade, while antiarrhythmic at the cellular level, was inherently proarrhythmic in the setting of a propagating wave front as a result of prolongation of the vulnerable period during which premature stimulation can initiate reentrant activation. From a theoretical perspective, sodium (depolarizing) and potassium (repolarizing) currents are complementary so that if antiarrhythmic and proarrhythmic properties are coupled to modulation of sodium currents, then antiarrhythmic and proarrhythmic properties might similarly be coupled to modulation of potassium currents. The purpose of the present study was to explore the role of repolarization currents during reentrant excitation. To assess the generic role of repolarizing currents during reentry, we studied the responses of a two-dimensional array of identical excitable cells based on the FitzHugh-Nagumo model, consisting of a single excitation (sodium-like) current and a single recovery (potassium-like) current. Spiral wave reentry was initiated by use of S1S2 stimulation, with the delay timed to occur within the vulnerable period (VP). While holding the sodium conductance constant, the potassium conductance (gK) was reduced from 1.13 to 0.70 (arbitrary units), producing a prolongation of the action potential duration (APD). When gK was 1.13, the tip of the spiral wave rotated around a small, stationary, unexcited region and the computed ECG was monomorphic. As gK was reduced, the APD was prolonged and the unexcited region became mobile (nonstationary), such that the tip of the spiral wave inscribed an outline similar to a multipetaled flower; concomitantly, the computed ECG became progressively more polymorphic. The degree of polymorphism was related to the APD and the configuration of the nonstationary spiral core. Torsadelike (polymorphic) ECGs can be derived from spiral wave reentry in a medium of identical cells. Under normal conditions, the spiral core around which a reentrant wave front rotates is stationary. As the balance of repolarizing currents becomes less outward (eg, secondary to potassium channel blockade), the APD is prolonged. When the wavelength (APD.velocity) exceeds the perimeter of the stationary unexcited core, the core will become unstable, causing spiral core drift. Large repolarizing currents shorten the APD and result in a monomorphic reentrant process (stationary core), whereas smaller currents prolong the APD and amplify spiral core instability, resulting in a polymorphic process. We conclude that, similar to sodium channel blockade, the proarrhythmic potential of potassium channel blockade in the setting of propagation may be directly linked to its cellular antiarrhythmic potential, ie, arrhythmia suppression resulting from a prolonged APD may, on initiation of a reentrant wave front, destabilize the core of a rotating spiral, resulting in complex motion (precession) of the spiral tip around a nonstationary region of unexcited cells. In tissue with inhomogeneities, core instability alters the activation sequence from one reentry cycle to the next and can lead to spiral wave fractination as the wave front collides with inhomogeneous regions. Depending on the nature of the inhomogeneities, wave front fragments may annihilate one another, producing a nonsustained arrhythmia, or may spawn new spirals (multiple wavelets), producing fibrillation and sudden cardiac death.

Ventricular fibrillation is not always due to multiple wavelet reentry.

It is not known whether ventricular fibrillation (VF) is always caused by multiple wavelet reentry, or if it could also be caused by a single wandering reentrant wavefront. Activation mapping of the entire ventricles during VF is practically impossible. We studied VF in a two-dimensional sheet of left ventricular subepicardial tissue of isolated, Langendorff-perfused pig hearts. Left and right endocardial cryoablation via probes filled with liquid nitrogen caused coagulation necrosis of the right ventricle, interventricular septum, and most of the left ventricular wall, leaving a thin subepicardial layer intact. Left ventricular epicardial activation patterns were constructed based on simultaneous recording of 128 unipolar extracellular electrograms. Regular pacing through a central electrode before and after freezing revealed that, following cryoablation, the activation pattern no longer showed evidence of involvement of the Purkinje system, and that it was compatible with propagation through a two-dimensional anisotropic tissue sheet. VF was induced by burst pacing. When the mass of surviving subepicardium was < 10 g, no VF could be induced; when it was between 10 and 20 g, VF was nonsustained; when it was > 20 g, VF was sustained. Unipolar extracellular electrograms during VF before and after cryablation could not be distinguished from each other; however, epicardial activation patterns were markedly different. In the intact left ventricle, up to six different wavefronts were simultaneously present during a 100-msec time window. In the "frozen heart," during a period of about 0.5 seconds, at most two wandering reentrant waves were simultaneously present; sometimes only one reentrant wave was seen in a 100-msec time window. The extracellular waveform during VF can be caused by different forms of reentry: multiple wavelet reentry (on the order of six different wavefronts), two independent wandering reentrant waves, and a single wandering reentrant wave.

Electrophysiological Effects of Flecainide on Anisotropic Conduction and Reentry in Infarcted Canine Hearts

The class IC antiarrhythmic drug flecainide has been shown to be ineffective for the treatment of ventricular arrhythmias in some patients who have had a prior myocardial infarction and sometimes even provoke arrhythmias (proarrhythmic effect). Since some ventricular tachycardias may be caused by anisotropic reentry, we determined the effects of flecainide on this mechanism for reentry in infarcted canine hearts in order to determine possible causes for its clinical effects. The effects of flecainide were determined on ventricular tachycardia induced by programmed electrical stimulation in dogs with healing myocardial infarction 4 days after coronary artery occlusion. Activation in the reentrant circuits causing tachycardia was mapped with a 196-channel computerized mapping system. We found that flecainide converted inducible unsustained ventricular tachycardia to inducible sustained ventricular tachycardia by modifying conduction in the reentrant circuit. In general, by slowing conduction, the reentrant wave front did not block after flecainide, leading to perpetuation of reentrant excitation. When sustained ventricular tachycardia could be induced before the drug, flecainide prolonged the coupling interval of premature impulses necessary to induce tachycardia by lengthening the line of block and slowing conduction around it. Flecainide also slowed the rate of the tachycardia but did not terminate it. The anisotropic reentrant circuits were modified so that the central common pathway of "figure-of-eight" circuits was narrowed and lengthened due to extension of the lines of block that bounded the pathways. Extension of the lines of block resulted from depression of conduction in the direction transverse to the long axis of the myocardial fiber bundles caused by flecainide. Flecainide also slowed conduction in the longitudinal direction in part of the circuits. The depressant effects of flecainide on both longitudinal and transverse anisotropic conduction were quantified by pacing from the center of the electrode array and it was found, contrary to predictions, that transverse conduction was depressed as much as longitudinal conduction. Flecainide slows conduction in both the longitudinal and transverse direction relative to the orientation of the myocardial fibers. This enables sustained reentry to occur more easily. Flecainide does not cause conduction block in crucial regions of reentrant circuits (central common pathway) and therefore does not prevent reentrant tachycardia in healing infarcts.