Rate-related suppression and facilitation of conduction in isolated canine cardiac Purkinje fibers

Previous studies have shown that antegrade conduction through damaged His Purkinje tissue may be suppressed following rapid ventricular pacing (overdrive suppression of conduction). We studied this phenomenon using isolated Purkinje fibers placed in a three-chamber bath. Superfusates for the left, middle, and right segments of the fiber were altered to produce action potentials that resembled those of normal bundle branch, damaged His bundle, and normal His bundle, respectively. To produce anisotropic conduction, the left segment of the fiber was adjusted to be three to four times longer than the right segment. Pacing the right segment at intermediate rates produced maximal action potential amplitude in the middle segment and 1:1 right-to-left conduction, whereas pacing at faster or slower rates reduced action potential amplitude and produced block. Pacing the left segment at fast or slow rates also reduced action potential amplitude in the middle segment, but conduction was maintained (anisotropy). After rapid or slow left segment pacing, action potential amplitude in the middle segment remained low during subsequent right segment pacing at intermediate rates, and transient block occurred (overdrive or underdrive suppression of conduction). With time, action potential amplitude normalized and conduction resumed. In other more severely depressed preparations, conduction block occurred even at intermediate right segment pacing rates prior to left segment pacing. Under these conditions, pacing the left segment at intermediate rates increased action potential amplitude in the middle segment and temporarily permitted 1:1 conduction at intermediate right segment pacing rates (overdrive facilitation of conduction).(ABSTRACT TRUNCATED AT 250 WORDS)     

Premature escape beats induced by overdrive pacing in canine Purkinje fibers. Evidence for the role of normal automaticity as an underlying cellular mechanism.

Premature escape beats induced in conscious dogs with chronic complete atrioventricular block have been defined as escape beats occurring on cessation of overdrive pacing and having a coupling interval to the last paced beat shorter than the coupling interval between the premature escape beat and the second postpacing beat. Triggered activity has been proposed as the primary underlying mechanism. We used standard microelectrode techniques to study the effects of overdrive pacing on normal automatic canine Purkinje fibers to determine if premature escape beats could be induced and if so, to define the underlying cellular mechanism(s). For this purpose, we overdrive-paced Purkinje fibers for 10 and 50 seconds and for 10 and 50 beats at a pacing cycle length (PCL) of 1,000-200 msec. In addition, to help distinguish among major arrhythmogenic mechanisms, we used a matrix of drugs consisting of propranolol, nadolol, lidocaine, ethmozin, and doxorubicin. Fifty-second stimulation trains induced "classic" overdrive suppression of the first three postpacing impulses, whereas 10-second overdrive pacing induced significant overdrive suppression only at a PCL of 200 msec. With 50-beat overdrive pacing and a PCL of 1,000-600 msec, there was overdrive suppression of postpacing impulses, whereas reduced overdrive suppression was observed at a PCL of 400-200 msec. Ten-beat stimulation trains induced a "flat response" of postpacing impulses. Ten- and 50-beat overdrive pacing provoked premature escape beats in 66% of the fibers, with the higher incidence at a PCL of 200 msec for 50-beat stimulation trains. No shortening of the coupling interval of premature escape beats was observed at faster pacing rates. Only lidocaine (which suppresses normal automaticity) abolished premature escape beats. We conclude that normal automaticity is the most likely mechanism underlying premature escape beats in Purkinje fibers with high levels of membrane potential.     

Purkinje fibre-papillary muscle interaction in the genesis of triggered activity in a guinea pig model.

OBJECTIVE: Previous studies have attempted to characterise the genesis of triggered activity related to early afterdepolarisations. Little is known about their conduction behaviour. This study was designed to examine the origin and conduction behaviour of triggered activations to throw light on the pathogenesis of torsade de pointes. METHODS: Electrophysiological interactions related to triggered activations and early afterdepolarisations between papillary muscle and Purkinje fibres were studied in the guinea pig in a single chambered bath. EDTA (5 mM) in Tyrode's solution was used and microelectrodes were placed in both papillary muscle and Purkinje fibres. RESULTS: During early superfusion, marked prolongation of action potential duration and early afterdepolarisations occurred in Purkinje fibres but not in papillary muscle. In addition: (1) with prolongation of action potential duration and early afterdepolarisations in Purkinje fibres, triggered activations arose during phase 2 and were conducted to papillary muscle, where they induced activations; (2) the number of papillary muscle discharges increased with the increase in Purkinje fibre action potential duration in a linear correlation; (3) severing a segment of papillary muscle from Purkinje fibres eliminated these papillary muscle activations; (4) some triggered activations did not conduct to papillary muscle; these had smaller amplitude, slower rate of depolarisation (dV/dt), more positive activation voltage, and similar peak voltages compared to conducted triggered activations; (5) a low plateau resulting from electrotonic interaction was recorded at the Purkinje fibre-papillary muscle junction; this plateau may have facilitated conduction of triggered activations. CONCLUSIONS: In this preparation there was a disparity of effect on Purkinje fibre and papillary muscle. Prolongation of action potential duration and repetitive activations due to early afterdepolarisations originated in Purkinje fibres and were conducted to papillary muscle. Purkinje fibre-papillary muscle interactions are of interest in relation to torsade de pointes arrhythmias which are believed to arise from this mechanism.     

On the mechanisms by which hypoxia eliminates digitalis-induced tachyarrhythmias

The mechanism by which hypoxia abolishes the tachyarrhythmiasinduced by cardiac steroids was studied in cardiac Purkinjeand ventricular muscle fibres. In muscle fibres, hypoxia reducesexcitability markedly, reduces the size and increases the timeto peak of the oscillatory potentials (V_os) and of the aftercontractions induced by cardiac steroids, thereby abolishingthe tachyarrhythmias. In Purkinje fibres, hypoxia also decreasesVos and excitability but abolishes the tachyarrhythmias onlyif repeated or prolonged. In Purkinje-muscle preparations, hypoxiablocks impulse conduction from the fast discharging Purkinjefibres to the myocardial fibres when the latter are still littleintoxicated. It is concluded that hypoxia affects promptly ventricular musclefibres and (depending on the experimental conditions) Purkinjefibres also, and readily blocks impulse transmission to musclefibres. Hypoxia abolishes arrhythmias by decreasing Vos size(probably through an impaired calcium uptake into the sarcoplasmicreticulum), by causing a conduction block at the Purkinje-musclejunction (probably through an increase in cytoplasmic calcium)and by reducing excitability.     

Characteristics of initiation and termination of catecholamine-induced triggered activity in atrial fibers of the coronary sinus

We studied epinephrine-induced delayed afterdepolarizations and triggered activity in atrial fibers from the canine coronary sinus to determine whether their responses to cardiac pacing would aid in formulating a uniform set of guidelines for differentiating this triggered activity from other arrhythmogenic mechanisms. We used standard microelectrode techniques and compared the delayed afterdepolarizations and triggered activity with those occurring in ouabain-superfused Purkinje fibers. Like Purkinje fibers, the frequency of triggering in the coronary sinus and the coupling interval of the first triggered beat were related directly to the basic drive cycle length, and the delayed afterdepolarization amplitude and frequency of triggering were related to the coupling interval of premature stimuli (S2). However, unlike Purkinje fibers, the coupling interval of the delayed afterdepolarization and of the first triggered beat were independent of the S2. Once initiated, triggered activity in the coronary sinus followed one of four rhythm patterns: in all four, the minimum and equilibrium cycle lengths were independent of the initiating cycle length. Triggered activity was terminated by overdrive and S2 pacing, especially by long episodes of overdrive at short cycle length. The first escape beat after overdrive was linearly related to the overdrive cycle length, resulting in overdrive acceleration. The return cycle length after S2 was linearly related to the S2 coupling interval. Because delayed afterdepolarizations and triggered activity in the coronary sinus respond differently to pacing from those in ouabain-superfused Purkinje fibers, triggered activity in general may not be identified by a uniform set of guidelines.     

Modulation of the Purkinje-ventricular muscle junctional conduction by elevated potassium and hypoxia

Action potential transmission in the canine ventricle normally occurs from the Purkinje (P) system into the ventricular muscle (VM) at specific P-VM junction sites. Transitional (T) cells are located between the Purkinje and the ventricular (V) cells at these P-VM junction sites. It has been shown that exposure to elevated [K+]0 in combination with hypoxia produces an increase in the P-VM conduction time. To examine this increase in P-VM conduction time, simultaneous measurements of the action potential upstrokes of T cells and the activation times of the local P and V cells at P-VM junctional sites were obtained from in vitro canine papillary muscles. The effects of elevated [K+]0 and hypoxia on conduction from P cells to T cells was then compared with the conduction from T cells to V cells to assess the relative contribution of each to the increase in the P-VM conduction time. We found that this intervention has approximately equal effects on the two sequential steps involved in P-VM conduction. We then analyzed the increased delay from T cells and V cells on the basis of three hypothetical mechanisms: 1) increased coupling resistance, 2) decreased V cell excitability, and 3) decreased cellular responsiveness of the T cells. Our results show that the effects of elevated [K+]0 and hypoxia on T-VM delay can be accounted for by a decreased responsiveness of the T cells without any significant electrical uncoupling between T and V cells or decrease in VM excitability.     

Intraventricular conduction block induced by ischemia

The electrical consequences of experimental acute myocardial ischemia were studied in 50 dogs. The study was performed through unipolar epicardial leads and at different levels of the conducting system; bundle branch and Purkinje fibers. There is evidence that the block takes place at the Purkinje-muscle union or in the muscle-muscle conduction. In none of the experiments the block appeared in any of the components of the conducting system. Also, there is evidence that with severe ischemia muscle recordings disappeared while the Purkinje potentials remained unchanged, this suggests that conducting system cells are more resistant to hypoxia than the contractile cells. Ventricular arrhythmias usually appeared simultaneously with conduction blocks that favored reentries. Arrhythmias were more frequent when the blocks were more accentuated. Our data demonstrates that the conduction disorder precedes in some instances, the positive RS-T displacement and in others it hides the such displacement. It is concluded that the RS-T displacement, the distal conduction block and arrhythmias are manifestations, at different levels, of partial diastolic depolarization induced by acute myocardial ischemia.     

Sinus node sequences after atrial stimulation: similarities of effects of different methods.

Sinoatrial conduction is commonly assessed from features of the initial cycle after a single atrial extrastimulus or eight beats atrial pacing. In contrast, sinus node automaticity is assessed by the duration of the first interval after prolonged atrial pacing. The return cycle and initial sequences after these different methods were compared in 10 subjects with normal sinus node function and 30 patients with sick sinus syndrome. Typically, sequences after all three methods showed a maximally prolonged first interval with a progressive decrease over five or more cycles. A model of recovery from overdrive suppression was used to compute the elements of conduction time and automaticity in the first interval. The sequences which followed a single extrastimulus and pacing were similar, the only index which increased significantly with prolonged pacing was associated with the degree of suppression of automaticity. The computed component of sinoatrial conduction in the return cycle was similar for all three methods. Thus all three conventional methods which consider only the initial post-stimulation interval measure both sinoatrial conduction and sinus node automaticity. The separate components of automaticity and conduction may be assessed by analysis of the total sequence.     

Characterization of return cycle responses predictive of successful pacing-mediated termination of ventricular tachycardia

Objectives. The purpose of this study was to characterize response patterns during overdrive pacing that predict successful termination of ventricular tachycardia.Background. Overdrive pacing during ventricular tachycardia typically results in entrainment at slow pacing rates and in termination or acceleration at faster rates. The factors that determine the critical paced cycle length that results in tachycardia termination have not been extensively studied.Methods. Ventricular tachycardias in 14 patients with coronary artery disease were studied with overdrive pacing at several cycle lengths. Return cycles were measured after each additional paced beat at each paced cycle length. The return cycle responses during pacing trials that resulted in tachycardia termination and those that resulted in entrainment were compared.Results. Three return cycle responses were identified: flat, plateau and increasing. Twenty trials of overdrive pacing resulted in tachycardia termination; all were characterized by an increase in the return cycle with the delivery of each successive beat in the pacing drive until the tachycardia terminated (increasing response). Thirty-four pacing trials resulted in entrainment and not termination; these were characterized either by a constant return cycle (flat response) or an initial increase in return cycle followed by a longer, constant return cycle (plateau response) with the delivery of additional paced beats. The longest paced cycle length that resulted in tachycardia termination correlated with the relative refractory period of the circuit, defined as the tachycardia cycle length minus the fully excitable gap (r²= 0.764, p = 0.0001). Tachycardia termination was not observed unless the paced cycle length was shorter than the relative refractory period of the circuit.Conclusions. The critical paced cycle length that causes termination of ventricular tachycardia depends on the relative refractory period of the circuit because this factor determines whether the nth + 1 beat of the pacing drive will encounter partially recovered tissue. These data provide insights into the mechanism of pacing-mediated tachycardia termination and entrainment and are applicable to the development of improved antitachycardia pacing algorithms.     

Sinus node sequences after atrial stimulation: similarities of effects of different methods

Sinoatrial conduction is commonly assessed from features of the initial cycle after a single atrial extrastimulus or eight beats atrial pacing. In contrast, sinus node automaticity is assessed by the duration of the first interval after prolonged atrial pacing. The return cycle and initial sequences after these different methods were compared in 10 subjects with normal sinus node function and 30 patients with sick sinus syndrome. Typically, sequences after all three methods showed a maximally prolonged first interval with a progressive decrease over five or more cycles. A model of recovery from overdrive suppression was used to compute the elements of conduction time and automaticity in the first interval. The sequences which followed a single extrastimulus and pacing were similar, the only index which increased significantly with prolonged pacing was associated with the degree of suppression of automaticity. The computed component of sinoatrial conduction in the return cycle was similar for all three methods. Thus all three conventional methods which consider only the initial post-stimulation interval measure both sinoatrial conduction and sinus node automaticity. The separate components of automaticity and conduction may be assessed by analysis of the total sequence.     

Triggered activity as a mechanism for inherited ventricular arrhythmias in German shepherd dogs

Objectives.This study sought to determine whether early after-depolarization-induced triggered activity is responsible for the initiation of ventricular arrythmias in dogs with an inherited predisposition to sudden death.Background.We have identified a colony of German shephered dogs that display inherited ventricular ectopic activity and sudden cardiac death. The arrhythmias in these animals are pause dependent but are not associated with a prolonged QT interval, suggesting that they might be initiated by early afterdepolarization-induced triggered activity in Purkinje fibers.Methods.Cardiac Purkinje fibers obtained from dogs that either did or did not exhibit ventricular tachyarrhythmias at the time of study were superfused in vitro with normal. Tyrode solution (extracellular potassium ion concentration 4 mmol/liter) and were studied using standard microelectrode techniques.Results.Early afterdepolarizations and triggered activity occurred spontaneously in Purkinje fibers obtained from affected dogs (n = 7) but not in fibers obtained from unaffected dogs (n = 13). Exit conduction block of triggered responses occurred to varying degrees within the Purkinje fiber but not at the Purkinje-muscle junction. Overdrive pacing suppressed triggered activity. The reemergence of triggered activity after cessation of pacing was both time and rate dependent. Triggered activity in fibers obtained from affected dogs was potentiated by phenylephrine and epinephrine and was suppressed by isoproterenol. Triggered activity was not induced by phenylephrine or epinephrine in fibers obtained from unaffected dogs.Conclusions.These results support the hypothesis that early afterdepolarization-induced triggered activity in Purkinje fibers is responsible for the initiation of ventricular arrhythmias in this canine model of inherited sudden death.     

Comparative effects of overdrive on sinus and subsidiary pacemaker function.

Recent evidence has suggested a difference in response to overdrive pacing dependent on the location of the pacemaker within the A-V conduction system. To test this hypothesis, the effects of overdrive pacing were evaluated in five anesthetized dogs with experimentally induced A-V block and in seven patients with advanced A-V block. In the animals, sinoatrial node recovery times were studied over wide ranges of rates (130 to 210 beats per minute) and durations (30 to 180 seconds) of atrial pacing. All sinus node recovery times were less than 600 msec. with a mean maximum pause of 0.540+/-0.043 seconds (M.+/-S.E.M.). In contrast, after ventricular pacing (rates 90 to 150 beats per minute; durations 30 to 180 seconds), subsidiary pacemaker recovery times were significantly greater (p less than 0.025) with a mean maximum recovery time of 28.4+/-8.3 seconds. In the seven patients studied, all sinus node recovery times were less than 1,400 msecs. with a mean maximum pause of 0.954+/-0.051 seconds. As seen with the experimental animals, a significantly longer (p less than 0.025 mean maximum subsidiary pacemaker recovery time of 3.55+/-0.92 seconds was observed. The present studies in both experimental animals and in man without evidence of sinus node dysfunction showed that sinus node recovery time was independent of both rate and duration of atrial overdrive pacing. In contrast, subsidiary pacemaker recovery time was correlated with both rate and duration of ventricular overdrive pacing. In both experimental protocols, subsidiary pacemaker recovery time was shown to exceed sinus node recovery time at all rates and at all durations of pacing. Postrecovery sinus node acceleration was consistently observed after atrial overdrive pacing. In contrast, postrecovery subsidiary pacemaker "depression" characterized ventricular overdrive pacing. It is concluded that subsidiary pacemakers are significantly more susceptible to overdrive suppression than the sinoatrial node, a feature of substantial clinical significance.     

Closed chest permanent atrioventricular block in dogs

Ten mongrel dogs underwent transcutaneous His bundle ablation by means of pulsed synchronized electrical shocks delivered between an electrode catheter adjacent to the His bundle and a metal plate behind the dog's back. Detailed histologic studies were performed 3 months after induction of stable complete atrioventricular (AV) block in nine dogs. The ventricular response ranged from 35 to 51 beats/min (bpm). Graded increases in overdrive ventricular pacing resulted in graded increases in pacemaker suppression up to a paced cycle length of 450 msec. All dogs showed extensive damage to the approaches to the AV node, the AV node, and the penetrating portion of the common bundle. This technique resulted in complete AV block with typical features of an infranodal pacemaker and correlated with the histologic findings of severe damage to the AV junction. The minimal myocardial damage suggests that this technique may be applicable for control of drug refractory supraventricular arrhythmias in humans.     

Effects of propafenone on sinus nodal and ventricular automaticity: in vitro and in vivo correlation

The electrophysiologic effects of the new antiarrhythmic drug, propafenone, were evaluated in anesthetized closed-chest dogs and on isolated cardiac tissues with the microelectrode technique. Propafenone (2 to 4 mg/kg intravenously) had no effect on sinus rate or on sinus nodal recovery time, but caused a dose-dependent significant decrease in the rate of idioventricular rhythm and increased the duration of ventricular overdrive suppression in dogs (n = 8) with complete atrioventricular block. On isolated canine Purkinje fibers (n = 8) manifesting automaticity with resting membrane potential less negative than -70 mV, propafenone reduced the slope of phase 4 depolarization and reduced the rate of automatic impulse initiation in a concentration-dependent manner (10(-6) M-4.10(-5) M). At these concentrations, propafenone had no effect on rabbit sinus nodal automaticity (n = 8) or on sinoatrial conduction. However, significant depression of sinus nodal automaticity occurred with propafenone concentrations above 5.10(-6) M in the presence of cholinergic or complete autonomic blockade with atropine (10(-6) M) and propranolol (5.10(-5) M). Propafenone caused a concentration-dependent decrease in the disparity of Purkinje fiber-ventricular muscle action potential duration (APD), mainly by shortening Purkinje fiber APD. We conclude: that propafenone suppresses idioventricular rhythm in the intact dog, most likely by depressing Purkinje fiber automaticity; the depressant effect of propafenone on sinus nodal automaticity is evident only during cholinergic receptor blockade; and the antiarrhythmic properties of propafenone may include removal of APD disparity by selective shortening of Purkinje fiber and not of ventricular muscle APD.     

Ventricular conduction delay and asystole during systemic hyperkalemia

Systemic hyperkalemia was induced in 30 intact dogs to evaluate electrophysiologic and hemodynamic alterations caused by excess of potassium (K⁺) ion. Sequential changes included atrioventricular junctional delay and block, followed by acceleration of junctional pacemakers and conduction delays in the ventricular specialized tissue and ventricular muscle. These resulted in unusual arrhythmias difficult to interpret in the peripheral electrocardiogram. As the level of potassium progressively rose, terminal Purkinje or Purkinje-muscle block was the dominant mechanism of arrest, with conduction through the ventricular specialized conduction system continuing at a regular rate even after asystole. The duration and amplitude of the intramural complexes were consistently reduced throughout the heart wall, whereas intramural conduction was progressively prolonged with late and inconstant changes in activation sequence. Ventricular pacing thresholds increased progressively, but were attainable even after asystole in some cases. The enhanced plasma K⁺ was associated with accumulation of K⁺ and sodium (Na⁺) in myocardial tissue. A relatively uniform distribution of these ions from endocardium to epicardium is postulated to be a requirement for progressive conduction delay, lack of ectopic beats and asystole. Systemic arterial pressure and coronary blood flow were maintained until very high levels of K⁺ were reached. Although left ventricular end-diastolic pressure increased progressively, the maximal rate of rise of left ventricular pressure (dP/dt max) was reduced only at a K⁺ level of 11 mEq/liter. Myocardial ischemia was not present, thus suggesting that the abnormal ventricular function may have been secondary to conduction delays.     

Induction and termination of triggered activity by pacing in isolated canine Purkinje fibers

The clinical importance of delayed afterdepolarizations and resultant triggered activity as a cause of cardiac arrhythmias is uncertain. We studied the response of ouabain-induced delayed afterdepolarizations and triggered activity to a pacing protocol similar to those used clinically in an effort to quantify the types of responses to pacing that occur as a result of this arrhythmogenic mechanism. Isolated canine Purkinje fibers were superfused with 2 X 10(7)M ouabain until delayed afterdepolarizations occurred and attained an amplitude of 5 mV at a paced cycle length of 500 msec. We then studied the induction of triggered activity in these fibers by pacing. We found that: (1) As the pacing cycle length decreased, the coupling interval from the last paced beat to the first triggered beat decreased and 83% of fibers developed triggered activity. (2) The coupling interval of the first triggered beat after single (S2) or double (S2S3) premature beats was in part dependent on preceding pacing cycle lengths. S2 pacing induced triggered activity in 39% of fibers, and S2S3 pacing induced triggered activity in 48% of fibers. We then studied the termination of ouabain-induced sustained rhythmic activity by pacing: 89% of sustained rhythmic activity could be terminated by overdrive pacing at a cycle length less than or equal to 300 msec. The coupling interval of the first beat or first delayed afterdepolarization after the termination of overdrive decreased as pacing cycle length decreased. S2 premature beats reset the sustained rhythmic activity and terminated 14% of sustained rhythmic activity. The coupling interval of the first escape beat or delayed afterdepolarization after S2S3 premature beats decreased as the S2S3 interval shortened, and S2S3 terminated 26% of sustained rhythmic activity. Pacing at an S1S1 cycle length of 400 msec followed by an S2 terminated 50% of sustained rhythmic activity; S1S1 at a cycle length of 400 msec followed by S2S3 terminated 85% of sustained rhythmic activity. This quantitative demonstration of the responses of delayed afterdepolarizations, triggered activity, and sustained rhythmic activity to pacing may be useful in differentiating these from other mechanisms for arrhythmias.     

The cellular basis of intrinsic sinus node recovery time

STUDY OBJECTIVE--The aim was to investigate the mechanism of the intrinsic sinus node recovery time. DESIGN--The effect of 2 min periods of 20% and 50% overdrive on the electrical activity of fibres in the sinoatrial node was studied in isolated atria of rabbits under complete autonomic blockade (atropine 3 x 10(-6) M and propranolol 3 x 10(-7) M). EXPERIMENTAL MATERIAL--Rabbits (New Zealand white) of either sex up to 3 kg weight were used. MEASUREMENTS AND MAIN RESULTS--The first returning cycle after overdrive is prolonged not only by the time needed for retrograde plus antegrade conduction but also by a delay in impulse formation (overdrive suppression). During pacing, action potential duration, amplitude, maximum diastolic potential (only in primary pacemaker fibres), and diastolic depolarisation rate were all decreased. Action potential duration, amplitude and maximum diastolic potential returned to control value during the first cycle following a period of overdrive, but diastolic depolarisation remained depressed during many consecutive cycles. In primary pacemaker fibres, diastolic depolarisation appeared to be depressed throughout diastole. In latent pacemaker fibres diastolic depolarisation was depressed only in the second part of the diastole. CONCLUSIONS--Sinus node recovery time has two components: (1) a conduction component of both retrograde and antegrade conduction, and (2) a depression of the automaticity (= overdrive suppression), which is only due to a slowing of diastolic depolarisation.     

Electrophysiologic determinants of recurrent atrial flutter after successful termination by overdrive pacing

The potential ability of electrophysiologic abnormalities to predict recurrence of atrial flutter was evaluated. Twenty-five patients with chronic atrial flutter resistant to combined digitalis and quinidine therapy were studied electrophysiologically after restoration of sinus rhythm by overdrive pacing or by eventual direct current cardioversion. Recurrence of atrial flutter was observed in 12 patients during a mean follow-up period of 17 months (range 3 to 50). Electrophysiologic testing included programmed high right atrial stimulation at a paced drive cycle length of 600 ms and incremental pacing up to 200-ms paced intervals. When coupling intervals of 90% of the drive cycle length were compared to coupling intervals of 48% of the drive cycle length, the increase in S1A1 interval, defined as the interval between the stimulus artifact and the atrial activation near the atrioventricular junction, was greater in patients with subsequent recurrence of atrial flutter (47 +/- 11 vs 21 +/- 18 ms). Stepwise logistic regression analysis identified the S1A1 increase to be the sole independent predictor of recurrence (p = 0.0082) while previous episodes of atrial flutter or the presence of organic heart disease were identified as dependent variables. Reclassification showed a 91% sensitivity and a 92% specificity. Correct classification was achieved in 92% of patients. The initiation of atrial dysrhythmia had no predictive value. The assessment of the S1A1 interval by programmed atrial stimulation appears helpful in delineating the patient risk of recurrent atrial flutter after termination by overdrive pacing.     

Overdrive suppression of antegrade conduction over the accessory pathway

In a patient with Wolff-Parkinson-White syndrome whose accessory pathway was primarily capable of bidirectional conduction, antegrade conduction over the accessory pathway was transiently inhibited after rapid atrial or ventricular pacing or after spontaneous termination of atrioventricular reentrant tachycardia. Pacing rate and duration of tachycardia were related to the duration of the suppression of preexcitation, while the coupling interval of the first sinus beat to the last driven or tachycardia beat was irrelevant to the phenomenon. Thus, overdrive suppression of conduction may be the most likely mechanism of this phenomenon.     

Overdrive suppression of implanted pacemakers in patients with AV block.

Patients being permanently paced for symptomatic AV block were studied by overdrive suppression of the QRS-inhibited pacemaker, in order to observe the underlying heart rhythm. The chest wall stimulation method was used. In complete AV block the escape rhythm recovery time proved highly reproducible on repeated testing on the same day, and in many patients remained so over months or years. Occasionally, a doubling of the escape rhythm recovery time was seen, suggesting initial exit block of the escape focus. Resetting of the escape rhythm usually followed an exponential curve until stabilisation after about 3 minutes. An early escape rhythm with a recovery time of less than 4 seconds was found on every occasion in 21 of 58 patients with complete AV block, and inconstantly in 23 more; in 14 it was never observed. Accidental pacing failure was seen in 15 patients. The overdrive suppression test was helpful in selecting pacemaker dependent patients.