Reentrant Extrasystole Research Articles

Brugada syndrome and ischemia-induced ST-segment elevation. Similarities and differences

Introduction ST-Segment elevation is a common electrocardiogram (ECG) manifestation of acute transmural myocardial ischemia in leads facing the injury. Acute myocardial ischemia involving the right-ventricular (RV) outflow tract is known to induce a Brugada-like ECG. In this paper, we examined the electrophysiological bases for the similarities between the ECG characteristics of the Brugada syndrome model induced by terfenadine (5 μmol/L) and the ECG manifestations of the acute transmural no-flow ischemia model. Methods For both experimental simulations, we used isolated arterially perfused canine RV wedge preparations to record transmembrane action potentials (AP) from endocardium and epicardium together with a transmural pseudo-ECG (ECG); basic cycle length = 400 to 2000 ms. Results In the presence of a prominent I to-mediated AP notch, no-flow ischemia causes true ST-segment elevation because of selective depression and loss of the AP dome at some epicardial sites. In the absence of a prominent AP notch, ischemia ultimately produces an apparent ST-segment elevation, which is secondary to a prolongation of the R wave caused by marked transmural conduction delays. Similarly, in the Brugada syndrome model generated in preparations displaying a large epicardial I to, ST-segment elevation was due to loss of the epicardial AP dome at some sites but not at others. Transmural conduction delay giving the appearance of ST-segment elevation is also observed in the Brugada model in preparations exhibiting smaller AP notch. In both models, propagation of the dome from the site at which it is maintained to a site at which it is lost may result in closely coupled phase 2 reentrant extrasystoles. Conclusion Our results suggest that I to can modulate the electrocardiographic manifestation of acute ischemia as well as that of the Brugada syndrome, and that both clinical entities are the result of a similar electrophysiological substrate.

Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation.

The Brugada syndrome is characterized by marked ST-segment elevation in the right precordial ECG leads and is associated with a high incidence of sudden and unexpected arrhythmic death. Our study examines the cellular basis for this syndrome. Using arterially perfused wedges of canine right ventricle (RV), we simultaneously recorded transmembrane action potentials from 2 epicardial and 1 endocardial sites, together with unipolar electrograms and a transmural ECG. Loss of the action potential dome in epicardium but not endocardium after exposure to pinacidil (2 to 5 micromol/L), a K(+) channel opener, or the combination of a Na(+) channel blocker (flecainide, 7 micromol/L) and acetylcholine (ACh, 2 to 3 micromol/L) resulted in an abbreviation of epicardial response and a transmural dispersion of repolarization, which caused an ST-segment elevation in the ECG. ACh facilitated loss of the action potential dome, whereas isoproterenol (0.1 to 1 micromol/L) restored the epicardial dome, thus reducing or eliminating the ST-segment elevation. Heterogeneous loss of the dome caused a marked dispersion of repolarization within the epicardium and transmurally, thus giving rise to phase 2 reentrant extrasystole, which precipitated ventricular tachycardia (VT) and ventricular fibrillation (VF). Transient outward current (I(to)) block with 4-aminopyridine (1 to 2 mmol/L) or quinidine (5 micromol/L) restored the dome, normalized the ST segment, and prevented VT/VF. Conclusions-Depression or loss of the action potential dome in RV epicardium creates a transmural voltage gradient that may be responsible for the ST-segment elevation observed in the Brugada syndrome and other syndromes exhibiting similar ECG manifestations. Our results also demonstrate that extrasystolic activity due to phase 2 reentry can arise in the intact wall of the canine RV and serve as the trigger for VT/VF. Our data point to I(to) block (4-aminopyridine, quinidine) as an effective pharmacological treatment.

Mechanism of ventricular extrasystoles with fixed coupling: A theoretical model derived from the concept of longitudinal dissociation in the reentrant pathway of extrasystoles

An electrocardiogram taken from a 29-year-old man with old myocardial infarction is presented as an exemplary case of ventricular extrasystoles with fixed coupling. To explain the mechanism of ventricular extrasystoles with fixed coupling, a theoretical model is derived from the concept of longitudinal dissociation in the reentrant pathway. In the model, functional longitudinal dissociation divides the reentrant pathway into dual pathways F and S. When a sinus impulse is blocked in pathway F and passes only through pathway S, it becomes a manifest reentrant extrasystole because of marked conduction delay in pathway S. When the sinus rate does not exceed a certain value, such an impulse always becomes a manifest extrasystole with fixed coupling. Part of the impulse passing through pathway S enters pathway F retrogradely. In some cases, thereafter, it reenters pathway S and initiates ventricular reentrant tachycardia. When, on the other hand, a sinus impulse passes through both of pathways F and S, it becomes a concealed reentrant extrasystole because of insufficient conduction delay in the pathways.

Intermittent ventricular parasystolic bigeminy accompanied by reentrant ventricular extrasystoles

An extremely rare case of intermittent ventricular parasystolic bigeminy is presented, in which coexisting reentrant ventricular extrasystoles of sinus origin, showing mainly trigeminy, and those of ventricular parasystolic origin, showing a close coupling to the ventricular parasystolic beat, are demonstrated. Such a unique case has never been reported. Timely parasystolic exit block occurring just prior to the anterograde ventricular activation of the sinus impulse was considered to be of critical importance in developing the reentrant extrasystolic trigeminy.

The paradox of sudden slowing of idioventricular rhythm during exercise in complete heart block: Modulation of automatic focus, concealed reentry, or wedensky inhibition?

As a rule, exercise enhances the rate of discharge of idioventricular rhythms in complete atrioventricular (AV) block. The opposite effect, a sudden drop in the rate of discharge with subsequent resetting of the firing rate, was observed in an 18-year-old boy with chronic complete AV block. Two mechanisms for this paradoxical response to exercise are proposed: (1) delay in discharge of the automatic pacemaker focus by successful penetration of electrotonic potentials from nonconducted P waves across the area of block in the AV conduction system and into the pacemaker focus; and (2) discharge of the pacemaker focus by concealed reentrant extrasystoles. Wedensky inhibition is ruled out because of the resetting of the firing rate.

Mechanism of supraventricular parasystole.

Two patients with supraventricular parasystole (one atrioventricular and one auricular) are reported. In both patients, reentrant extrasystoles appeared to occur as the result of Mobitz type I second-degree entrance block. We believe that when a sinus impulse fell soon after the absolute refractory period of the pathway containing the parasytolic focus, it reached and discharged the focus after marked delay, and thereafter became a reentrant extrasystole. In interectopic intervals containing more than one sinus beat, the number of intervening sinus beats was always even, suggesting the presence of concealed reentrant extrasystolic bigeminy. The observations in the present report and in our previous patients with ventricular parasystole strongly suggest that most cases of parasystole, whether ventricular or supraventricular, or whether intermittent or "continuous," may be governed by second-degree entrance block.

Mechanisms of ventricular parasystole.

Eight cases of ventricular parasystole are reported. In all these cases, regardless of whether parasystole seems intermittent or "continuous," the presence of second degree entrance block of the Mobitz type I was suggested. Parasystole alternated with concealed extrasystolic bigeminy showing occasional reentrant extrasystoles. Such intermittent parasystole appears to originate in the reentrant path of extrasystoles. Reentrant extrasystolic bigeminy was seen in a comparatively rapid sinus rhythm, whereas parasystolic bigeminy was seen in a comparatively slow sinus rhythm. The difference between the interectopic intervals during parasystolic bigeminy and during (manifest or concealed) extrasystolic bigeminy was comparatively small so that occasionally the difference was not distinct; on such an occasion the case showed a seemingly "continuous" parasystole. These observations strongly suggest the possibility that most cases of parasystole, whether intermittent or "continuous," may be governed by incomplete entrance block of the second degree.

Intermittent Parasystole Originating in the Reentrant Path of Ventricular Extrasystoles

This report indicates the presence of intermittent ventricular parasystole alternating with ventricular extrasystoles caused by the reentrant mechanism, in which the parasystolic focus is located within the reentrant path. Intermittent parasystole in this case shows second-degree entrance block. When a sinus impulse falls in the absolute refractory period of the ventricular-ectopic junction, the ectopic focus is protected from it. When a sinus impulse falls in a considerably late period of the ectopic cycle, which is long after the absolute refractory period of the ventricular-ectopic junction, the parasystolic rhythm is also not disturbed by it. Although in this late period the sinus impulse enters the ventriculare-etopic junction, it interferes with the next ectopic impulse within the junction and therefore cannot reach the ectopic focus. When a sinus impulse falls before the previously mentioned period but still long after the absolute refractory period of the ventricular-ectopic junction, it reaches the ectopic focus after a comparatively short time of ventricular-ectopic conduction, which results in resetting of the parasystolic rhythm; however, when a sinus impulse falls shortly after the absolute refractory period of the ventricular-ectopic junction, it reaches the ectopic focus after a marked delay in conduction, and thereafter it occasionally becomes a reentrant extrasystole.