Overdrive Stimulation Research Articles

219-01: The subcutaneous ICD in congenital heart disease – challenges and chances

Purpose of the study: Transvenous ICD therapy faces relevant limitations and contraindications in patients with congenital heart disease (CHD). The recently introduced entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) offers a relevant alternative, as it does not need vascular access or thoracotomy. Methods used: S-ICD system was implanted in a heterogeneous group of 10 patients with structural CHD (age 8.9–62.0 y, height 73.0–208.0 cm, weight 34.0–130.0 kg). The majority presented with challenging hemodynamic and anatomical features such as univentricular anatomy, cavo-pulmonary anastomosis, dextrocardia, severe scoliosis, mechanical circulatory support (VAD due to failing systemic right ventricle in cc-TGA) and tricuspid valve dysplasia (Ebstein's anomaly); one patient suffered from Tetralogy of Fallot (TOF) with multiple previous surgery and another from juvenile HOCM. In 9 of 10 patients ICD was implanted due to secondary prophylaxis. Primary indication to opt for S-ICD as the first choice were: missing transvenous access (2), right-to-left shunt as contraindication for transvenous leads (4), avoidance of tricuspid valve passage (2) and young age without pacing indication (1). In one patient (with VAD) a pre-existing transvenous ICD had been removed due to chronic lead-associated infection and replaced by a right-sided S-ICD, combined with epicardial pacing. All patients were eligible by surface ECG template screening. Lead and device positioning was anatomically adapted and modified by pre-implant fluoroscopy to achieve an optimized intrathoracic electric field. Two systems were implanted in mirrored position in patients with dextrocardia, one lead was placed right parasternal and 9 of 10 devices implanted submuscular. Summary of results: After uneventful implantation successful DFT testing applying a 15 J safety margin confirmed correct function in all. Follow-up was performed up to 5 years. Cosmetic results were good with no pocket-related issues even in the smallest subjects. 3 patients – all with RBBB - suffered from inappropriate shocks due to altered T wave morphology under higher heart rate resulting in t-wave-oversensing (TWOS). This could be overcome by acquiring a new template under maximum exercise. The patient with TOF had multiple appropriate shocks from monomorphic VTs but also developed slow VTs below the shock zone (<170/min) and severe chronotropic incompetence. Therefore he was switched to a transvenous system with improved clinics due to the availability of pain free overdrive stimulation (ATP) and antibradycardiac pacing. The VAD patient died during follow-up of unknown reason. Conclusion: S-ICD therapy is feasible even in complex CHD patients, for whom conventional transvenous ICD concepts are not applicable. As this may avoid risks and burden associated with surgical lead placement, it represents an attractive new therapeutic modality. Due to the vast heterogeneity in size and anatomy, together with frequent alterations in excitation propagation and repolarization in this group, an advanced and thorough pre-implantation screening is mandatory. Modifications in lead and device arrangement supported by preoperative fluoroscopy are necessary, to ensure correct arrhythmia detection and therapy delivery even in distorted anatomy. The presumably higher incidence of TWOS has to be considered, although modified programming may resolve the issue. With submuscular placement, cosmetic and functional results are excellent; nevertheless the bulky size of the device currently precludes its use below a weight of approx. 30 kg. Despite successful application with combined (epicardial) pacing, the lack of antibrady- and -tachycardiac pacing currently represents the major limitation towards widespread use in the field of CHD.

EP News: Basic and Translational

Faggioni et al (Circ Res 2013;112:689, PMID 23295832) tested the hypothesis that catecholaminergic polymorphic ventricular tachycardia (CPVT) is suppressed by supraventricular overdrive stimulation. Using CPVT mouse models (Casq2−/−and RyR2(R4496C)+/−mice), the effect of increasing sinus heart rate was tested by pretreatment with atropine and by atrial overdrive pacing. Increasing intrinsic sinus rate with atropine and atrial overdrive pacing suppressed ventricular arrhythmias (VAs) in both CPVT models. In 6 of 18 patients with CPVT, VAs were paradoxically suppressed as sinus heart rates increased further with continued exercise. The authors conclude that accelerated supraventricular rates suppress VAs in 2 CPVT mouse models and in a subset of patients with CPVT. Hypothetically, atrial overdrive pacing may be a therapy for preventing exercise-induced VT in treatment-refractory patients with CPVT.

Accelerated Sinus Rhythm Prevents Catecholaminergic Polymorphic Ventricular Tachycardia in Mice and in Patients

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) genes. Sinoatrial node dysfunction associated with CPVT may increase the risk for ventricular arrhythmia (VA). To test the hypothesis that CPVT is suppressed by supraventricular overdrive stimulation. Using CPVT mouse models (Casq2(-/-) and RyR2(R4496C/+) mice), the effect of increasing sinus heart rate was tested by pretreatment with atropine and by atrial overdrive pacing. Increasing intrinsic sinus rate with atropine before catecholamine challenge suppressed ventricular tachycardia in 86% of Casq2(-/-) mice (6/7) and significantly reduced the VA score (atropine: 0.6±0.2 versus vehicle: 1.7±0.3; P<0.05). Atrial overdrive pacing completely prevented VA in 16 of 19 (84%) Casq2(-/-) and in 7 of 8 (88%) RyR2(R4496C/+) mice and significantly reduced ventricular premature beats in both CPVT models (P<0.05). Rapid pacing also prevented spontaneous calcium waves and triggered beats in isolated CPVT myocytes. In humans, heart rate dependence of CPVT was evaluated by screening a CPVT patient registry for antiarrhythmic drug-naïve individuals that reached >85% of their maximum-predicted heart rate during exercise testing. All 18 CPVT patients who fulfilled the inclusion criteria exhibited VA before reaching 87% of maximum heart rate. In 6 CPVT patients (33%), VA were paradoxically suppressed as sinus heart rates increased further with continued exercise. Accelerated supraventricular rates suppress VAs in 2 CPVT mouse models and in a subset of CPVT patients. Hypothetically, atrial overdrive pacing may be a therapy for preventing exercise-induced ventricular tachycardia in treatment-refractory CPVT patients.

Dynamic ventricular overdrive stimulation in atrial fibrillation: effects on ventricular rate irregularity, ventricular pacing, and fusion beats

In pacemaker patients with preserved atrio-ventricular (AV) conduction, atrial fibrillation (AF) can lead to symptomatic ventricular rate irregularity and loss of ventricular stimulation. We tested if dynamic ventricular overdrive (DVO) as a potentially pacemaker-integrated algorithm could improve both aspects. Different settings of DVO and ventricular-ventricular-inhibited-pacing (VVI) with different base rates were tested in two consecutive phases during electrophysiological studies for standard indications. Mean heart rate (HR), HR irregularity and percentage of ventricular pacing were evaluated. A fusion index (FI) indicative of the proportion of fusion beats was calculated for each stimulation protocol. Dynamic ventricular overdrive from the right ventricular apex was acutely applied in 38 patients (11 females, mean age 62.1 ± 11.5 years) with sustained AF and preserved AV conduction. Dynamic ventricular overdrive at LOW/MEDIUM setting increased the amount of ventricular pacing compared with VVI pacing at 60, 70, and 80 beats per minute (bpm; to 81/85% from 11, 25, and 47%, respectively; P < 0.05). It also resulted in a maximum decrease in interval differences (to 48 ± 18 ms from 149 ± 28, 117 ± 38, and 95 ± 46 ms, respectively; P < 0.05) and fusion (to 0.13 from 0.41, 0.42, and 0.36, respectively; P < 0.05) compared with VVI pacing at 60, 70, and 80 bpm. However, the application of DVO resulted in a significant increase in HR compared with intrinsic rhythm and VVI pacing at 80 bpm (to 97 bpm from 89 and 94 bpm, respectively; P < 0.05). Dynamic ventricular overdrive decreases HR irregularity and increases ventricular pacing rate compared with VVI pacing at fixed elevated base rates and spontaneous rhythm. Fusion index might help to refine information on pacing percentages provided by device counters.

Clinidine-induced bradycardia: studies of the effect on the human sinus node (author's transl)

Heart rate, atrioventricular conduction, sinus-node recovery time and effectiveness of carotid-sinus massage on heart rate were measured before and every five minutes after intravenous injection of 0.15 mg clonidine (Catapresan) in 11 patients (averaged age 60 years) with symptomatic bradycardia (dizzy spells, syncope, palpitations). Th results indicated the following significant (P less than 0.05) mean maximal effects: heart rate fell by 12% (from 59 to 52/min), capacity of atrioventricular conduction by 9% (from 132 to 121/min), while maximal sinus-node recovery time ("over-drive suppression") doubled (from 1704 to 3562 ms), heart rates of 120, 150 and 200/min being used for diagnostic atrial overdrive stimulation at each five-minute period after clonidine. During clonidine administration three patients developed a so-called hypersensitive carotid sinus reflex, in two patients the effectiveness of carotid sinus massage decreased, in three if increased, while in three it remained normal. It is concluded that (1) during bradycardia, initiated or increased by sympatholytic drugs, tests should be undertaken to exclude latent sinus-node syndrome and (or) hypertensive carotid-sinus reflex; (2) clonidine should not be used in patients with signs of sinus-node dysfunction.

A42-2 Prevention of atrial fibrillation by optimized overdrive stimulation — the PAFOS study

A42-2 Prevention of atrial fibrillation by optimized overdrive stimulation — the PAFOS study

A42-2 Prevention of atrial fibrillation by optimized overdrive stimulation - the PAFOS study

A42-2 Prevention of atrial fibrillation by optimized overdrive stimulation - the PAFOS study

Comparison of single premature versus continuous overdrive stimulation for identification of a protected isthmus in macro-reentrant atrial tachycardia circuits

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The Influence of Concomitant Drug Therapy on the Efficacy of Atrial Overdrive Stimulation for Prevention of Atrial Tachyarrhythmias

Data from the completed "Suppression of Atrial Fibrillation by DDD+ Overdrive Pacing with Inos2 CLS (closed-loop system) Pacemakers" multicenter trial were retrospectively evaluated to examine the influence of concomitant antiarrhythmic drugs on the clinical success of conventional single site right atrial overdrive pacing compared with DDD pacing. The DDD+ overdrive algorithm provided > 90% atrial pacing at a rate slightly above the intrinsic atrial rate. Seventy-five patients with conventional pacing indications and paroxysmal, recurrent atrial tachyarrhythmia have completed the study. They were randomized to 6 months of DDD or DDD+ pacing, followed by mode crossover and an additional 6-month follow-up in the alternate mode. The incidence of atrial tachyarrhythmia during each period was compared using data on sustained (> 60 s) mode switch episodes stored in the pacemaker memory. A stable antiarrhythmic drug regimen was allowed during the study. beta-Adrenergic blockers and Class III antiarrhythmics, prescribed to 54.7% and 40.0% of patients respectively, were linked to minimal or no benefit of overdrive pacing compared with DDD pacing. In contrast, patients untreated with beta-adrenergic blockers or Class III drugs had a significant reduction in atrial tachyarrhythmia burden of > 5 hours/patient per week (P < 0.05) during overdrive. Changes with Class I and Class IV antiarrhythmic drugs, prescribed to 18.7% and 13.3% of patients, respectively, were insignificant. Our data indicate that clinical trials that prohibit the use of beta-adrenergic blockers may record more favorable outcomes with dynamic atrial overdrive algorithms versus conventional DDDR pacing, than studies allowing concomitant beta-adrenergic blockade.

REMODELING OF Na,K-ATPase, AND MEMBRANE FLUIDITY AFTER ATRIAL FIBRILLATION IN SHEEP

ABSTRACTAtrial fibrillation (AF) is accompanied by various changes in ion channels that cause atrial electrophysiological remodeling. The enzyme Na,K-ATPase is also a major cellular mechanism for the regulation of ion homeostasis. During AF, Na,K-ATPase may be regulated by synthesis of its α- and β-subunits as well as changes in membrane fluidity. To test this hypothesis, we studied the effect of pacing-induced AF in sheep on atrial Na,K-ATPase α- and β-subunits and on membrane fluidity as well. Methods: A group of six sheep (AF group) was subjected to overdrive electrical stimulation of the right atrium in order to induce AF. A group of six sham operated sheep served as control. All paced sheep developed multiple episodes of sustained AF with a mean total duration of 110 min over a 2-hours period. Protein expression of Na,K-ATPase α- and β-subunits in atrial microsomal membranes was assayed by Western blotting analysis. When significant changes in membrane expression were observed, transcriptional regulation was analysed by Northern blotting. Membrane fluidity was assessed on atrial microsomal fractions by anisotropy measurements using the fluorescent probe diphenylhexatriene. Results: Atrial fibrillation enhanced the expression of the Na,K-ATPase β1-subunit at both membrane and mRNA levels. Anisotropy values were higher in AF group than in control group, indicating a decreased fluidity of the membranes isolated from paced sheep atria. Conclusion: These data are the first evidence for an enhanced Na,K-ATPase β1-subunit expression in membrane during AF. Membrane rigification represents a new factor of tachycardia-induced atrial remodeling.

Prevalence of left atrial chamber and appendage thrombi in patients with atrial flutter and its clinical significance

OBJECTIVESThe study was done to assess the prevalence of left atrial (LA) chamber and appendage thrombi in patients with atrial flutter (AFl) scheduled for electrophysiologic study (EPS), to evaluate the prevalence of thromboembolic complications after transesophageal echocardiographic (TEE)-guided restoration of sinus rhythm and to evaluate clinical risk factors for a thrombogenic milieu.BACKGROUNDRecent studies showed controversial results on the prevalence of atrial thrombi and the risk of thromboembolism after restoring sinus rhythm in patients with AFl.METHODSBetween 1995 and 1999, patients with AFl who were scheduled for EPS were included in the study. After transesophageal assessment of the left atrial appendage and exclusion of thrombi, an effective anticoagulation was initiated and patients underwent EPS within 24 h.RESULTSWe performed 202 EPSs (radiofrequency catheter ablation, n = 122; overdrive stimulation, n = 64; electrical cardioversion, n = 16) in 139 consecutive patients with AFl. Fifteen patients with a thrombogenic milieu were identified. All of them had paroxysmal atrial fibrillation (AF). Transesophageal echocardiography revealed LA thrombi in two cases (1%). After EPS no thromboembolic complications were observed. Diabetes mellitus, arterial hypertension and a decreased left ventricular ejection fraction were found to be independent risk factors associated with a thrombogenic milieu.CONCLUSIONSThe findings of a low prevalence of LA appendage thrombi (1%) in patients with AFl and a close correlation between a history of previous embolism and paroxysmal AF support the current guidelines that patients with pure AFl do not require anticoagulation therapy, whereas patients with AFl and paroxysmal AF should receive anticoagulation therapy. In addition, the presence of clinical risk factors should alert the physician to an increased likelihood for a thrombogenic milieu.

Catheter ablation of atrial flutter due to amiodarone therapy for paroxysmal atrial fibrillation

Antiarrhythmic drug treatment for atrial fibrillation can cause atrial flutter-like arrhythmias. The aim of this study was to clarify the effect of catheter ablation of the tricuspid annulus-vena cava inferior isthmus on amiodarone-induced atrial flutter and to determine the incidence of atrial fibrillation after catheter ablation of amiodarone-induced atrial flutter in comparison to regular typical flutter. Among 92 consecutive patients with typical atrial flutter who underwent isthmus ablation 28 patients had atrial flutter without a history of previous atrial fibrillation (group I), 10 patients had atrial flutter following the initiation of amiodarone therapy for paroxysmal atrial fibrillation (group II) and 54 patients had atrial flutter and atrial fibrillation (group III). Atrial cycle length during atrial flutter in amiodarone-treated patients (group II) (277+/-24 ms) was significantly longer as compared to the cycle length of atrial flutter in group I (247+/-33 ms) and group III patients (235+/-28 ms). The rate of successful transient entrainment and overdrive stimulation to sinus rhythm was not different between patients with (60%) or without amiodarone therapy (group I: 71%, group III: 53%). Successful isthmus ablation with bidirectional conduction block eliminating right atrial flutter was achieved in 90% of amiodarone-treated patients and 93% of patients without amiodarone therapy. In the amiodarone-treated patient group atrial conduction times during pacing in sinus rhythm were significantly prolonged by 20-30% before and after ablation in all regions of the reentrant circuit. During a mean follow-up of 8+/-3 months post-ablation, atrial fibrillation recurred in two of 10 patients on continued amiodarone therapy after successful isthmus ablation. Thus, successful catheter ablation of atrial flutter due to amiodarone therapy was associated with a markedly lower recurrence rate of paroxysmal atrial fibrillation (20%) as compared to patients with atrial flutter plus preexisting paroxysmal atrial fibrillation (76%) and was similar to the outcome of patients with successful atrial flutter ablation without preexisting atrial fibrillation (25%). These data suggest that isthmus ablation with bidirectional block and continuation of amiodarone therapy is an effective therapy for the treatment of atrial flutter due to amiodarone therapy for paroxysmal atrial fibrillation.

Value and safety of ambulatory electrophysiologic study

One-hundred-thirty patients underwent 53 electrophysiological studies including programmed atrial and ventricular stimulation and 96 atrial overdrive stimulations on an outpatient basis. The indications for electrophysiological study were disabling palpitation, syncope, or presyncope, intracardiac conduction disturbance, and bradyarrhythmia. In one patient the efficacy of oral antiarrhythmic drug therapy was evaluated by repeat electrophysiological study. Atrial overdrive stimulation was performed in patients with atrial flutter or atrial tachycardia. On the basis of the result of electrophysiological testing, 25 patients were believed not to require any treatment, 16 patients received new drug therapy, 7 patients underwent catheter ablation in a second session, 2 patients had either a pacemaker or an ICD implanted, and 1 patient continued to receive the drug therapy that had been tested. Atrial overdrive stimulation resulted in a regular sinus rhythm in 66 patients (69%). Except for one patient in whom atrial flutter could not be terminated, atrial fibrillation was induced in the remaining 30 patients. After the procedure, patients were monitored for 30 min in case of overdrive stimulation, and for approximately 3 h after electrophysiological study or 6 h if additional coronary angiography had been performed. Severe complications were not observed. In 10 cases minor hematoma occurred at the puncture site without serious sequelae.--Outpatient electrophysiological study as well as atrial overdrive stimulation are feasible and safe in a selected group of patients.

Antiarrhythmic Effects of Magnesium on Rat Papillary Muscle and Guinea Pig Ventricular Myocytes

1. Despite widespread use of magnesium ion (Mg 2+) for antiarrhythmic purposes, little direct information is available regarding its antiarrhythmic mechanisms. To elucidate the possible cellular mechanism, the effects of Mg 2+ on early afterdepolarization (EAD), delayed afterdepolarization (DAD), triggered activity (TA), transient inward current (TI) and aftercontraction (AC) were examined in various cardiac preparations. The effects of Mg 2+ on myoplasmic Ca 2+ concentration were also studied. 2. The effects of Mg 2+ on AC, induced by overdrive stimulation, were studied in isolated rat ventricular papillary muscle superfused with low K + solution. In enzymatically isolated guinea pig myocytes, EAD, DAD and/or TA were induced after overdrive stimulation under conditions of superfusion with low K + solution, using the whole-cell current-clamp method, and TI was also induced by the whole-cell voltage-clamp method. 3. Immediately after changing the solutions, containing varying concentrations of Mg 2+, the effects of Mg 2+ were examined. In addition, effects of Mg 2+ on Ca transient were studied, using fura-2. 4. We found that: (1) in the rat papillary muscle, 10 mM Mg 2+ effectively inhibited AC, which was produced after stimulation at both 3.3 Hz and 5 Hz, although 5 mM Mg 2+ was without effect in the case of AC induced after 5-Hz stimulation; (2) in the myocytes, 5 mM Mg 2+ did not inhibit DADs, EADs and TA, but 10 mM Mg 2+ inhibited them completely; (3) the amplitude and frequency of TI decreased significantly in the presence of 10 mM Mg 2+; and finally (4) 10 mM Mg 2+ inhibited the Ca transient underlying DAD and/or TA. 5. The findings suggest, but do not prove unequivocally, that Mg’s actions are probably due to a combination of a shift of the threshold of various ion channels to less negative potentials, a decrease in Ca 2+ influx via Ca channels, a block of several K channels, and/or a block of Na–Ca exchanger. In conclusion, the present study indicates that extracellular Mg 2+, via whatever mechanism, exerts antiarrhythmic activities.

The effect of overdrive pacing rate and duration on ventricular escape rhythms in patients with chronic complete atrioventricular block.

The effect of overdrive (OD) pacing rate and duration on subsidiary pacemakers was evaluated in 54 patients with third-degree AV block. They had a permanent pacemaker implanted 61 +/- 56 months earlier because of complete AV block in 38 patients and, in 16 patients because of second-degree AV block, which in the interim advanced to complete AV block. The patients had a reliable infranodal escape rhythm, with a mean cycle length of 2,022 +/- 603 msec, upon discontinuation of the ventricular OD pacing, at a rate of 40 beats/min. The escape interval and escape rhythm cycle length was evaluated after OD pacing at 40, 50, 60, 70, 90, and 100 beats/min for 30 seconds, at each rate. In 100% of the patients the subsidiary pacemaker recovered after OD pacing at 40 and 50 beats/min and the number decreased to 59% at a rate of 100 beats/min. The escape interval prolonged gradually between OD pacing at 40 and 100 beats/min, by 56%. The effect of OD pacing duration at 50 and 70 beats/min was evaluated. At an OD pacing rate of 70 beats/min there was a significant effect of the pacing duration on the escape interval. There were significant differences in the escape interval duration and escape rhythm cycle length between males and females, patients with or without coronary artery disease, and patients with narrow or wide QRS escape. However, the increase in the OD pacing rate had a similar effect on the escape interval in the above mentioned groups. There was no effect on the paced QRS duration and sinus cycle length at each OD pacing rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of overdrive stimulation on functional reentrant circuits causing ventricular tachycardia in the canine heart: mechanisms for resumption or alteration of tachycardia.

The purpose of the experiments described in this article was to investigate the effects of overdrive stimulation on functional anisotropic reentrant circuits causing ventricular tachycardia in infarcted canine ventricles. We determined how overdrive stimuli affect reentrant circuits to alter characteristics of the tachycardia. Activation patterns were determined by mapping excitation with a 192 bipolar electrode array. We found that overdrive stimuli could activate the circuits with the same pattern as the reentrant wavefront and that after overdrive stopped either the last or the next to last stimulated wavefront continued propagating through the circuit as a new reentrant impulse and tachycardia continued. When the circuit was not altered after overdrive, the exit route that the stimulated wavefront took from the circuit to activate the rest of the ventricles was also not altered and the tachycardia after overdrive had the same cycle length and QRS morphology as prior to overdrive. In some experiments, however, the overdrive stimuli did not follow the original reentrant pathway but led to the formation of a different circuit with a different exit route to the ventricles. As a result, after overdrive stimulation tachycardia had a different QRS morphology and cycle length than prior to stimulation. When the new circuit after overdrive was small and the revolution time of the reentrant impulse around the circuit was short, fibrillation occurred. Functional reentrant circuits can either be maintained or altered after a period of overdrive stimulation. The results explain many of the effects that have been seen during overdrive stimulation of clinical ventricular tachycardia.

Effects of High Frequency Stimulation on Cardiac Tissue with an Inexcitable Obstacle

We study numerically the effects of high-frequency stimulation in excitable cardiac tissue with an inexcitable obstacle using a Fitz-Hugh Nagumo type model. We show that if the frequency of stimulation is sufficiently high and the size of the inexcitable obstacle is sufficiently large, then a re-entrant pattern can be initiated. We also show that with overdrive stimulation a re-entrant pattern can be removed provided there are no obstacles at which new re-entrant patterns are created.

Overdrive stimulation of functional reentrant circuits causing ventricular tachycardia in the infarcted canine heart. Resetting and entrainment.

Clinical electrophysiology studies have used, for the most part, models of anatomic reentrant circuits to explain entrainment of ventricular tachycardia. Our studies use activation maps to directly determine mechanisms of entrainment of functional circuits that cause tachycardia. Electrograms were recorded from 192 sites on reentrant circuits in the epicardial border zone of canine myocardial infarcts during sustained ventricular tachycardia. Overdrive stimulation from different sites and at different cycle lengths was investigated. The reentrant circuits were shown to be functional, yet stimulated impulses could enter and repetitively reset the circuits (entrainment), demonstrating the presence of an excitable gap. Entrainment could occur from different stimulation sites with the stimulated impulses from each site activating the circuit with a different pattern. Entrainment, however, did not occur when the stimulated wave fronts obliterated the lines of functional block in the circuit. Fusion on the ECG occurred during entrainment when the stimulated impulses activated the ventricles concurrently with a previous stimulated impulse leaving the reentrant circuit at a different site. The first postpacing QRS was captured but not fused because it was caused by the last stimulated impulse emerging from the circuit. The first postpacing cycle length on the ECG was either equal to or longer than the overdrive cycle length depending on whether there was a fusion QRS during overdrive. The first postpacing cycle length at sites in the reentrant circuit equaled the pacing cycle length. At an appropriately short overdrive cycle length, stimulated impulses blocked in the circuit to terminate reentry. Functional reentrant circuits causing ventricular tachycardia can be reset and entrained. Activation maps directly show the mechanisms.

Rate Reduction by Overdrive Stimulation at the Origin of an Ectopic Ventricular Tachycardia in the Intact Pig Heart-Evidence of Vagal Activation

Rate Reduction by Overdrive Stimulation at the Origin of an Ectopic Ventricular Tachycardia in the Intact Pig Heart-Evidence of Vagal Activation

Effects of amiodarone on triggered activity induced by overdrive stimulation in Ca 2+ overloaded ventricular muscle from guinea pig

1. The acute effects of amiodarone, a powerful antiarrhythmic drug, on transient depolarizations (TDs) and/or triggered activity (TA) induced by an overdrive stimulation in the condition of low potassium (2.7 mM) and high calcium (5.4 mM) solution were evaluated on isolated ventricular papillary muscles from guinea pig, by means of conventional miocroeleetrode techniques. 2. The amplitude of the induced TDs was enhanced by increase in stimulus number and frequency during overdrive stimulation, and the coupling interval of TDs was shortened. 3. Amiodarone (4.4 × 10 −5 M) significatly decreased the amplitude of TDs, and prolonged the coupling interval. 4. On the other hand, superfusion with a higher concentration (4.4 × 10 −4) of amiodarone tended to induce automatic activity. 5. Possible implications with respect to the antiarrhythmic activity of amiodarone are discussed.