Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium.

BACKGROUND: Modification of spiral wave (SW) reentry by antiarrhythmic drugs is a central issue to be challenged for better understanding of their benefits and risks. OBJECTIVE: We investigated the effects of pilsicainide and/or verapamil, which block sodium and L-type calcium currents (I(Na) and I(Ca,L)), respectively, on SW reentry. METHODS: A two-dimensional epicardial ventricular muscle layer was created in rabbit hearts by cryoablation (n = 32), and action potential signals were analyzed by high-resolution optical mapping. RESULTS: During constant stimulation, pilsicainide (3-5 microM) caused a frequency-dependent decrease of conduction velocity (CV; by 20%-54% at 5 Hz) without affecting action potential duration (APD). Verapamil (3 microM) caused APD shortening (by 16% at 5 Hz) without affecting CV. Ventricular tachycardias (VTs) that were induced were more sustained in the presence of either pilsicainide or verapamil. The incidence of sustained VTs (>30 s)/all VTs per heart was 58% +/- 9% for 5 microM pilsicainide vs. 22% +/- 9% for controls and 62% +/- 10% for 3 microM verapamil vs. 22% +/- 8% for controls. The SWs with pilsicainide were characterized by slower rotation around longer functional block lines (FBLs), whereas those with verapamil were characterized by faster rotation around shorter FBLs. Combined application of 3 microM pilsicainide and 3 microM verapamil resulted in early termination of VTs (sustained VTs/all VTs per heart: 2% +/- 2% vs. 29% +/- 9% for controls); SWs showed extensive drift and decremental conduction, leading to their spontaneous annihilation. CONCLUSION: Blockade of either I(Na) or I(Ca,L) stabilizes SWs in a two-dimensional epicardial layer of rabbit ventricular myocardium to help their persistence, whereas blockade of both currents destabilizes SWs to facilitate their termination.

The sinus tachycardias.

Sinus tachycardia, in the forms of four distinct rhythm disturbances, is frequently encountered in clinical practice but is often overlooked. The most common rhythm, normal sinus tachycardia, whether physiologic, pathologic or iatrogenic, is predominantly catecholamine driven, is virtually asymptomatic and is managed by identifying and treating the underlying cause. The other so-called primary sinus tachycardias, which include inappropriate sinus tachycardia, postural orthostatic tachycardia syndrome and sinus node re-entry tachycardia, have fundamentally different clinical features, basic underlying etiologic mechanisms and treatment strategies. Differentiation of these types from normal sinus tachycardia and from other atrial arrhythmias is crucial for successful management. Accurate diagnosis and appropriate therapy of the sinus tachycardias not only prevents multiple consultations but might also have important long-term prognostic implications.

[Bradycardia-tachycardia syndrome during spinal anesthesia]. / Síndrome de bradicardia-taquicardia durante una anestesia espinal.

A 78-year-old man developed bradycardia with decreased level of consciousness followed by sinus arrest during femoropopliteal bypass surgery under subarachnoid anesthesia. Early in the recovery period, a similar clinical picture developed, with bradycardia but no change in level of consciousness. Sinus node automaticity or sinoatrial conduction abnormalities were suspected, and a 24-hour Holter electrocardiogram revealed bradycardia-tachycardia syndrome. The patient was prescribed amiodarone and anticoagulant therapy with acenocoumarol; no further episodes occurred during hospitalization. Bradycardia-tachycardia syndrome is a sinus node disorder that manifests intermittently. It can become apparent during or shortly after surgery, leading to problems of differential diagnosis.

"Sinus node" reentrant tachycardia associated with respiration.

A 77-year-old woman (case 1) and a 57-year-old woman (case 2) with paroxysmal "sinus tachycardia" are reported in whom the tachycardia repeatedly occurred associated with respiration. In both cases, reentrant P' waves are almost the same in configuration as sinus P waves, and P'R intervals are also the same in length as PR intervals. In case 1, the tachycardia was initiated during inspiration, and was terminated during expiration; showing tachycardia-dependent initiation. On the contrary, in case 2, the tachycardia was initiated during expiration, and was terminated during inspiration; showing apparent bradycardia-dependent initiation. Although exact diagnosis was not made by electrophysiologic studies, attempts were made to explain the mechanism of such unique tachyarrhythmias associated with respiration by using the concept of sinus node reentrant tachycardia as a possible mechanism.

Sinus node reentrant tachycardia in a neonate.

A neonate presented with paroxysmal atrial tachycardia. Transesophageal electrophysiological study demonstrated sinus node reentrant tachycardia, which was induced and terminated with programmed electrical stimulation. The tachycardia would also terminate in the atrium with adenosine. Empiric digoxin treatment successfully suppressed the tachycardia which then recurred with discontinuation of the digoxin at 6 weeks. The child was retreated with digoxin with no further recurrences for 18 months. Transesophageal electrophysiological study at 20 months showed prolonged sinus node recovery times and no inducible arrhythmias. The child has remained free of arrhythmias at 4 years.

Normal values for corrected sinus node recovery time in adolescents.

Sinus node recovery times have been used to evaluate sinus node function in adults and children. Normal values for corrected sinus node recovery time (CSNRT) are generally accepted as 275 and 500-550 msec in young children and adults, respectively. However, normal CSNRT values have not been determined for adolescent patients. Therefore, we mesured CSNRT in 29 consecutive patients, ages 12-17 years, who underwent electrophysiology testing as part of radiofrequency ablation. CSNRTs were performed by rapid atrial pacing for 30 seconds. Pacing cycle lengths were then shortened in 50-msec decrements to a minimum of 300 msec CSNRTs were determined by subtracting the patients' resting sinus cycle length from the maximal SNRT measured. The mean CSNRT was 323 +/- 61 msec (mean +/- SD, range 186-422 msec). A significant positive correlation between CSNRT and age was found. We conclude that the CSNRT value for the upper limit of normal in adolescents lies between the normal values previously determined for children and adults and is approximately 445 msec (mean + 2 SD). Because sinus node dysfunction is a well-recognized, long-term complication following surgical repair for complex congenital heart disease, this value becomes especially relevant as more children with congenital heart disease survive into adolescence.

[Cardiac electrophysiological effect and clinical use of adenosine]. / Az adenozin szív-elektrofiziológiai hatásai és klinikai alkalmazása.

A review is provided of the present state of knowledge relating to the cardiac electrophysiological effects of adenosine at ion channel and clinical levels. It is emphasized that intravenous adenosine is highly effective in terminating sinus node, atrioventricular (AV) nodal and AV-reciprocating reentrant tachycardias. In the course of an account of the antiarrhythmic indications of adenosine therapy, the main aspects of the diagnostic use of the nucleoside are briefly discussed. It is pointed out that adenosine treatment may possibly be accompanied by the occurrence of atrial and ventricular proarrhythmias, for at pharmacological dose of 6-12 mg this endogenous cardioprotective and antiarrhythmic agent is not devoid of side-effects.

Effect of intravenous amiodarone on electrophysiologic variables and on the modes of termination of atrioventricular reciprocating tachycardia in Wolff-Parkinson-White syndrome.

Atrioventricular reciprocating tachycardia (AVRT) associated with the Wolff-Parkinson-White (WPW) syndrome, sometimes terminates spontaneously, generally sustains and eventually becomes drug resistant. Amiodarone is a potent antiarrhythmic drug that is sometimes effective in patients with AVRT which is resistant to conventional antiarrhythmic drugs. However, systematic studies concerning the effects of amiodarone on AVRT have not been reported. This study evaluated the effects of intravenous amiodarone on electrophysiologic variables, and on the sites and the modes of termination of AVRT. Fifteen WPW patients were studied. Nine had overt, and 6 had concealed WPW syndrome. Measurements of electrophysiologic variables and the induction of AVRT were performed by atrial and/or ventricular programmed stimulations. Amiodarone was then administered at a dose of 5 mg/kg over 5 min. The effective refractory periods (ERP) of the atrial, atrioventricular node, ventricular and accessory pathway were increased significantly by amiodarone. The conduction times of all the components were significantly lengthened by amiodarone, except for the His-ventricular (HV) interval in concealed WPW patients. AVRT was induced in all patients, and was terminated by amiodarone in 12 of 13 patients with sustained AVRT. After amiodarone, AVRT was induced in 9 patients. Spontaneous termination was observed 11 times in 3 of the 9 patients in whom AVRT was still induced. In these cases, the modes and sites of termination were the same as during the baseline state. The ERPs and conduction times of all components of AVRT, except the HV interval, were significantly lengthened by amiodarone. Amiodarone is efficacious for terminating AVRT wherever weak links exist. However, sites of spontaneous termination are not significantly affected by amiodarone.

Results of a restrictive use of antiarrhythmic drugs in the chronic treatment of atrioventricular reentrant tachycardias in infancy and childhood.

Childhood supraventricular tachycardia (SVT) carries a good prognosis. Thus, treatment should be based on the use of drugs with a low risk of such potentially serious side effects as proarrhythmia, which is well documented for class I and III drugs in children. We studied all pediatric patients with a first manifestation of SVT between 1988 and the end of 1995 who were seen for a follow-up examination, including Holter monitoring, during 1996. The minimum follow-up period was 12 months. Fifty children met study entry criteria. Mean patient age at first presentation was 2 years (median 1 month), with 33 of the patients (66%) having experienced their first episode of tachycardia in their first year of life. Of 39 patients initially treated with either digoxin or a beta blocker, SVT in 29 (75%) responded favorably to this treatment. There were no adverse effects. Of the 10 children whose disease did not respond to these first-line agents, 9 (23% of those treated) required class I or III antiarrhythmic drugs. Thus, first-line antiarrhythmic long-term prophylaxis using drugs with a favorable risk profile, such as digoxin and beta blockers, resulted in successful disease management in a large proportion of unselected children, avoiding the need for chronic use of class I or class III antiarrhythmic drugs.

Adenosine as an antiarrhythmic agent.

Adenosine produces acute inhibition of sinus node and atrioventricular (AV) nodal function. This profound but short lived electrophysiologic effect makes adenosine a suitable agent for treating supraventricular tachycardias (SVT) that incorporate the sinus node or AV node as part of the arrhythmia circuit, or for unmasking atrial tachyarrhythmias or ventricular pre-excitation. Its antiadrenergic properties also make it an effective agent for use with some unique atrial and ventricular tachycardias. Appropriate dosing and rapid bolusing with intravenous administration is required. Recognition of infrequent proarrhythmic risks and potential drug interactions with xanthine derivatives and dipyridamole should maximize its safe and effective use. This review will highlight adenosine's mechanism of action, administration, clinical indications, efficacy, and risks when used in tachyarrhythmic management.

[The use of adenosine in the diagnosis and treatment of cardiac arrhythmias]. / Adenozin alkalmazása a szívritmuszavarok diagnosztikájában és kezelésében.

The authors investigated the effect of adenosine or ATP on narrow QRS tachycardia in 56 pts, 3 pts with wide QRS tachycardia 9 pts with suspected latent preexcitation and 10 pts with PVC suspected to be ventricular parasystole. After the bolus iv. administration of adenosine or ATP every SVT was stopped related to AV node (44 pts), but in the rest twelve related to atrial origin of SVT only one automatic atrial tachycardia could be stopped. From the 9 patient suspected to have concealed WPW 2 pts had delta wave during the effect of adenosine, and in four pts parasystole was demonstrated among the pts had varying coupling interval PVC. None of the pts who had wide QRS tachycardia was the tachycardia stopped, but in two cases the supraventricular origin--atrial flutter and tachycardia--was discovered. The authors emphasize the favourable effect of adenosine in narrow complex tachycardia and suggest that it can given safely in wide QRS tachycardia of unknown origin either. The diagnostic effect of adenosine can be used in sinus rhythm too if latent preexcitation or ventricular parasystole is suspected.

Action of antiarrhythmic agents on the area of slow conduction in ventricular tachycardia.

The most common mechanism of monomorphic sustained ventricular tachycardia (VT) is reentry with an excitable gap, but the electrophysiological properties and response to antiarrhythmic agents in the area of slow conduction are not yet fully known. The conduction time through the area of slow conduction may show a frequency-dependent delay in some VT but in others, constant conduction time was observed as the paced cycle length was decreased while VT was entrained. VT with a so-called decremental property could be terminated more often with rapid pacing with less risk of acceleration of the VT rate. When the excitable gap was estimated by the width of the zone of entrainment: defined as the difference between the cycle length of VT and the longest VT-interrupting paced cycle length during transient entrainment, there was no difference in the width of the zone of entrainment between the responders (VT induction was prevented with drugs) and the non-responders (VT remained inducible). The cycle length of VT was not a predictor of drug-efficacy. However, when the drug-effect was assessed at the intermediate doses, VT of those with a significantly narrowed width of the zone of entrainment were subsequently suppressed when the same drug was added. In conclusion, the electrophysiological properties of the area is diverse and it might affect pacing-induced terminability. Whether an antiarrhythmic agent is able to prevent VT-induction or not can not be predicted from the basal electrophysiologic parameters, but a significant narrowing of the width of the zone of entrainment, and hence the excitable gap, can be a hallmark for drug-efficacy.

Mechanism-specific effects of adenosine on atrial tachycardia.

BACKGROUND: Recent reports suggest that adenosine, in addition to terminating supraventricular tachycardia involving the atrioventricular (AV) node, may have antiarrhythmic effects on atrial tachycardia. The electrophysiological effects of adenosine on supraventricular tissue include shortening of action potential duration in atrial myocytes mediated by the potassium current, IKACh,Ado; shortening of action potential duration and hyperpolarization in sinus node cells; and anti-adrenergic electrophysiological effects resulting from inhibition of adenylyl cyclase. We therefore hypothesized that the response of atrial tachycardia to adenosine would be mechanism specific, with termination of atrial tachycardia due to sinus node reentry or cAMP-mediated triggered activity, transient suppression of automatic atrial tachycardia, and an absence of antiarrhythmic effect on tachycardia due to intraatrial reentry. METHODS AND RESULTS: Adenosine (mean +/- SD, 143 +/- 54 micrograms/kg IV) was administered to 27 patients (55 +/- 19 years) in atrial tachycardia whose mechanism was confirmed by electrophysiological study. Adenosine terminated sinus node reentrant tachycardia in 6 of 6 patients and terminated atrial tachycardia due to triggered activity in the 1 patient in whom it was identified. Adenosine transiently suppressed automatic atrial tachycardia in 7 of 7 patients and had no effect in 13 patients with intra-atrial reentrant tachycardia, including 8 patients with atrial flutter. CONCLUSIONS: These findings demonstrate that adenosine's effects on atrial tachycardia are mechanism specific and can be used to differentiate between reentrant tachycardia confined to the region of the sinus node or atria and between nonreentrant atrial tachycardia due to either triggered activity or automaticity.

Role of alterations in refractoriness and conduction in the genesis of reentrant arrhythmias. Implications for antiarrhythmic effects of class III drugs.

Despite the fact that a number of different electrophysiologic mechanisms are capable of causing cardiac arrhythmias, reentrant excitation has emerged as the most important mechanism causing life-threatening arrhythmias that arise in the ventricles. Pharmacologic therapy of arrhythmias caused by reentry is aimed at preventing the conditions that either facilitate the initiation of the circulating reentrant excitation wave or the conditions that permit its persistence. This involves alterations in either refractoriness or conduction by the drugs. Both atrial and ventricular tachyarrhythmias may follow premature depolarizations that occur at a critical coupling interval to a previous excitation. One desirable property of antiarrhythmic drugs might be to prevent the initiation of reentrant excitation by the triggering premature impulse. Mechanisms are described to show how drugs that prolong the action potential duration (class III antiarrhythmic drugs) might have this effect. It is, however, emphasized that drug effects that have been documented in electrophysiologic studies on normal myocardium might not occur in an arrhythmogenic region that has pathologic alterations, because of changes in the properties of ion channels of the diseased myocardial cells. Antiarrhythmic drugs might also terminate ongoing reentrant excitation by causing block of conduction in the reentrant pathway, at least for one beat. Class III drugs are expected to stop the perpetuation of reentry by prolonging the action potential duration and the refractory period of myocardial fibers in the reentrant circuit to such an extent that the propagating reentrant impulse no longer finds excitable myocardium but blocks in refractory tissue. Therefore, the effectiveness of this drug class to terminate reentry should depend on at least 2 factors: the size of the excitable gap as the reentrant impulse moves around the circuit, which may be related to the mechanism that causes reentry, and the degree to which the drugs can prolong the action potential duration and refractory period at the rapid rates of tachycardia. Each of these factors is discussed with relation to the proposed mechanism of action of drugs that prolong repolarization.

The effects of adenosine on sinus node reentrant tachycardia.

The effects of adenosine given during sinus node reentrant tachycardia were investigated in two patients. Both patients received intravenous bolus doses of 0.1 mg/kg and 0.15 mg/kg. Adenosine slowed the atrial rate in both patients and terminated the tachycardia in one. These effects of adenosine on sinus node reentrant tachycardia suggest that sinus nodal tissue (as opposed to perinodal atrial tissue) is involved in the tachycardia circuit and that these effects should be considered when adenosine is used as a diagnostic agent in narrow-complex tachycardia.

Comparison of the effects of intravenous and oral betaxolol on antegrade and retrograde conduction in patients with atrioventricular nodal reentrant and atrioventricular reentrant tachycardia.

The electrophysiologic effects of intravenous (0.15 mg kg-1) and oral (20 mg day-1) betaxolol have been investigated in 11 patients with atrioventricular (A-V) nodal reentrant tachycardia and eight patients with orthodromic A-V reentrant tachycardia. Betaxolol significantly (P greater than 0.01) prolonged sinus cycle length, sinus node recovery time, intranodal conduction time, and the antegrade functional refractory period of the A-V node. When the effective refractory period of the A-V node could be determined it was increased by betaxolol, whereas no significant electrophysiologic effects were observed in the atrium, the ventricle or the accessory pathway. Intravenous betaxolol prevented tachycardia in 8 out of 11 patients with A-V nodal reentrant tachycardia, whereas oral betaxolol was effective in 10 patients, primarily by acting on the antegrade limb in two patients and on the retrograde limb in eight patients. In those with A-V reentrant tachycardia, intravenous betaxolol did not prevent tachycardia in any patient, while it was effective after oral treatment in two patients. When the tachycardia remained inducible, cycle length of the tachycardia increased in all patients, due to prolongation of the antegrade and retrograde conduction time in patients with A-V nodal reentrant tachycardia, and due to an increase in the antegrade conduction time, i.e. the A-V node, in the patients with A-V reentrant tachycardia. In conclusion, betaxolol proved to be effective in the treatment of supraventricular tachycardia; for chronic treatment, a single oral dose (20 mg) seems to suffice.