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.

Progressive action potential duration shortening and the conversion from atrial flutter to atrial fibrillation in the isolated canine right atrium.

OBJECTIVES: We sought to evaluate the effects of progressive shortening of the action potential duration (APD) on atrial wave front stability. BACKGROUND: The mechanisms of conversion from atrial flutter to atrial fibrillation (AF) are unclear. METHODS: Isolated canine right atria were perfused with 1 to 5 micromol/l of acetylcholine (ACh). We mapped the endocardium by using 477 bipolar electrodes and simultaneously recorded transmembrane potentials from the epicardium. The APD(90) was measured during regular pacing (S(1)) with cycle lengths of 300 ms. Atrial arrhythmia was induced by a premature stimulus (S(2)). RESULTS: At baseline, only short runs of repetitive beats (<10 cycles) were induced. After shortening the APD(90) from 124 +/- 15 ms to 72 +/- 9 ms (p < 0.01) with 1 to 2.5 micromol/l of ACh, S(2) pacing induced single, stable and stationary re-entrant wave fronts (307 +/- 277 cycles). They either anchored to pectinate muscles (5 tissues) or used pectinate muscles as part of the re-entry (4 tissues). When ACh was raised to 2.5 to 5 micromol/l, the APD(90) was further shortened to 40 +/- 12 ms (p < 0.01); S(2) pacing induced in vitro AF by two different mechanisms. In most episodes (n = 13), AF was characterized by rapid, nonstationary re-entry and multiple wave breaks. In three episodes with APD(90) <30 ms, AF was characterized by rapid, multiple, asynchronous, but stationary wave fronts. CONCLUSIONS: Progressive APD shortening modulates atrial wave front stability and converts atrial flutter to AF by two mechanisms: 1) detachment of stationary re-entry from the pectinate muscle and the generation of multiple wave breaks; and 2) formation of multiple, isolated, stationary wave fronts with different activation cycle lengths.

Mechanisms of atrial fibrillation and flutter and implications for management.

Both electrophysiologic and anatomical substrates are important in the generation and maintenance of atrial fibrillation. This review discusses the nature of re-entrant wavefronts in atrial fibrillation and the importance of anatomical structures, such as the pectinate muscles, in the generation and maintenance of re-entry. The involvement of the pectinate muscle structure on intra-atrial re-entry may have significant implications for both ablation and pharmacologic management of patients with atrial fibrillation.

Role of electrophysiologic evaluation in patients with ventricular arrhythmias.

The decision to perform electrophysiologic testing in patients with ventricular arrhythmia should be based on the presence, if any, of underlying heart disease and the clinical type of ventricular arrhythmia. Clinical presentations range from asymptomatic premature ventricular complexes identified on routine surface ECG to out-of-hospital cardiac arrest. Ventricular arrhythmias range from benign monomorphic ventricular ectopy to polymorphic VT and ventricular fibrillation. The goal in evaluating patients with ventricular arrhythmia is to identify those at high risk of suffering a life-terminating arrhythmic event. Risk stratification should be based on history, physical examination, clinical data and the likelihood that anti-arrhythmic therapy will prevent symptoms and more importantly, prolong life. Noninvasive evaluation with routine surface ECG, Holter monitoring, signal-averaged ECG and echocardiography are valuable tools in the risk stratification process. However, electrophysiologic testing in most forms of ventricular tachyarrhythmia is the optimal means of diagnosing, risk stratifying and managing potentially life-threatening ventricular arrhythmias.

Influence of wavefront dynamics on transmembrane potential characteristics during atrial fibrillation.

INTRODUCTION: Although computerized mapping studies have demonstrated the presence of multiple wavelets during atrial fibrillation (AF) and that action potential amplitude and duration in AF vary significantly from beat to beat, no study has correlated the single cell action potential changes with the patterns of activation during AF. METHODS AND RESULTS: We studied wavefront dynamics and single cell transmembrane potential (TMP) characteristics in 12 isolated perfused canine right atria. The endocardial surface was mapped using 477 bipolar electrodes while TMP was recorded with a standard glass microelectrode from an epicardial cell. AF was induced in the presence of acetylcholine. Successful simultaneous TMP recordings and activation maps were made during six episodes of AF and for a total of 141 activations. Large variations of TMP amplitude and duration were observed frequently; 34% of them have a low amplitude (<50% of the amplitude recorded during pacing). Low-amplitude potentials were recorded when the impaled cell was (1) in an area of random reentry (67%, n = 36); (2) within 3.2 mm of the core of organized functional reentry (22%, n = 12); (3) in the middle of two merging wavefronts (9%, n = 5); and (4) at the point of spontaneous wavebreak (2%, n = 1). CONCLUSION: Large variations of TMP are observed frequently during in vitro AF. Low-amplitude TMPs are associated with specific patterns of AF activation wavefronts.

Transmembrane potential properties of atrial cells at different sites of a spiral wave reentry: cellular evidence for an excitable but nonexcited core.

Transmembrane action potentials (TAPs) were recorded during simultaneous mapping of a reentrant wavefront induced in canine isolated atria. The activation pattern was visualized dynamically using a high resolution electrode catheter mapping system. During functional reentry (spiral wave), cells in the core of the spiral wave remained quiescent near their resting membrane potential. Cells away from the core progressively gained TAP amplitude and duration, and at the periphery of the spiral wave the cells generated TAPs with full height and duration. During anatomical reentry, when the tip of the wavefront remained attached to the obstacle (a condition of high source-to-sink ratio), the TAP near the obstacle had normal amplitude and duration. However, when the tip of the wavefront detached from the obstacle (condition of lowered source-to-sink ratio) the TAP lost amplitude and duration. These results are consistent with the theory that the source-to-sink ratio determines the safety factor for wave propagation and wave block near the core. With decreasing source-to-sink ratio, TAP progressively decreases in amplitude and duration. In the center of the core, the cells, while excitable, remain quiescent near their resting potential. This decrease reflects a progressive decrease in the source-to-sink ratio. TAP vanishes in the core where cells remain quiescent near their resting potential. Functional and meandering reentrant wavefronts are compatible with the spiral mechanism of reentry where block at the rotating point is provided by the steep curvature of the wave tip.

Transmembrane potential properties at the core of functional reentrant wave fronts in isolated canine right atria.

BACKGROUND: The characteristics of transmembrane potential (TMP) at the core of functional reentry in the atrium are not well understood. METHODS AND RESULTS: In protocol 1 (11 dogs), isolated perfused canine right atria were mapped from the endocardial surface while simultaneous TMPs were recorded from the epicardial surface. Episodes of reentry (n=64) were induced in the presence of 1 to 5 micromol/L acetylcholine. Successful simultaneous TMP recordings and activation maps were made in 8 episodes. The TMP was "near the core" if it was within 3.2 mm of the core; otherwise, it was considered to be "in the periphery." The mean cycle length of reentry was 110+/-35 ms. The TMP amplitude, duration (90% repolarization), and (dV/dt)max near the core (n=106) were 58+/-22 mV, 46+/-14 ms, and 33+/-20 V/s, respectively, significantly less than those in the periphery (n=241): 70+/-8 mV, 94+/-32 ms, and 55+/-10 V/s (P<0.001 for all). In 2 episodes of reentry, the cell at the core remained unexcited at its resting membrane potential. In protocol 2 (2 dogs), we performed simultaneous high-density mapping in 4 episodes of reentry and showed synchronous activation patterns on both surfaces with similar locations of the core. CONCLUSIONS: During meandering functional reentry in isolated canine right atria, (1) TMPs of cells near the core have a reduced amplitude, duration, and (dV/dt)max, and (2) cells at the core may remain unexcited at their resting membrane potential. These findings are compatible with the spiral wave concept of functional reentry in the atrium.

Role of pectinate muscle bundles in the generation and maintenance of intra-atrial reentry: potential implications for the mechanism of conversion between atrial fibrillation and atrial flutter.

To determine the role of pectinate muscle (PM) bundles in the formation of intra-atrial reentry, 10 isolated canine right atrial tissues were perfused with Tyrode's solution containing 1 to 2.5 micromol/L acetylcholine (ACh). The endocardium was mapped using 477 bipolar electrodes with 1.6-mm resolution. Reentry was induced by a premature stimulus (S2). Computer simulation studies were used to investigate the importance of regional myocardial thickness in reentry formation. A total of 40 episodes of reentry were induced; 28 episodes were stationary, and the remaining 12 were nonstationary. The stationary reentry was induced either immediately after the S2 stimuli (n=9) or after an initial period of irregular activations that lasted 1460+/-1077 ms (n= 19). Of 28 episodes, 20 were initiated by conduction block along large PM ridges, leading to wave break and the initiation of reentry. The reentrant wave fronts remained stationary and rotated around these ridges as anchoring sites. During the transition from the initial irregular activations to stationary reentry, the electrogram morphology converted from "fibrillation-like" to "flutter-like" activity. In 8 episodes, initially stationary reentry converted to irregular activations because of interference with outside wave fronts (n=5) or spontaneous separation of waves from the ridges (n=3). Compared with stationary reentry, nonstationary reentry always occurred over an area without large PMs, and the mean life span was much shorter (102+/-151 versus 3.8+/-1.1 rotations, P<0.001). Computer simulation studies showed that a critical ridge thickness is needed for reentry to anchor, thereby converting fibrillation to flutter. We conclude that PM ridge forms an area where wave break occurs, allowing the initiation of reentry. It also provides a natural anchor to the reentrant wave front, lengthening the life span of reentry. The attachment and detachment of the reentrant wave front to and from the ridge determine "flutter-like" or "fibrillation-like" activity.

Relation between cellular repolarization characteristics and critical mass for human ventricular fibrillation.

INTRODUCTION: The critical mass for human ventricular fibrillation (VF) and its electrical determinants are unclear. The goal of this study was to evaluate the relationship between repolarization characteristics and critical mass for VF in diseased human cardiac tissues. METHODS AND RESULTS: Eight native hearts from transplant recipients were studied. The right ventricle was immediately excised, then perfused (n = 6) or superfused (n = 2) with Tyrode's solution at 36 degrees C. The action potential duration (APD) restitution curve was determined by an S1-S2 method. Programmed stimulation and burst pacing were used to induce VF. In 3 of 8 tissues, 10 microM cromakalim, an ATP-sensitive potassium channel opener, was added to the perfusate and the stimulation protocol repeated. Results show that, at baseline, VF did not occur either spontaneously or during rewarming, and it could not be induced by aggressive electrical stimulation in any tissue. The mean APD at 90% depolarization (APD90) at a cycle length of 600 msec was 227+/-49 msec, and the mean slope of the APD restitution curve was 0.22+/-0.08. Among the six tissues perfused, five were not treated with any antiarrhythmic agent. The weight of these five heart samples averaged 111+/-23 g (range 85 to 138). However, after cromakalim infusion, sustained VF (> 30 min in duration) was consistently induced. As compared with baseline in the same tissues, cromakalim shortened the APD90 from 243+/-32 msec to 55+/-18 msec (P < 0.001) and increased the maximum slope of the APD restitution curve from 0.24+/-0.11 to 1.43+/-0.10 (P < 0.01). CONCLUSION: At baseline, the critical mass for VF in diseased human hearts in vitro is > 111 g. However, the critical mass for VF can vary, as it can be reduced by shortening APD and increasing the slope of the APD restitution curve.