Single Premature Beats Research Articles

Enhanced sodium-calcium exchange enabled by an increase in the calcium transient in the presence of an abbreviated action potential: A new arrhythmia mechanism

Early afterdepolarizations (EADs) are observed in superfused canine pulmonary vein sleeves following norepinephrine (NE) (3.2 x 10−8 M) administration and tachycardia-pause pacing, interventions increasing the magnitude of the calcium transient. Further shortening of the already abbreviated pulmonary vein action potential by acetylcholine (10−7 M) enables the EADs to trigger arrhythmia formation. We examined the hypothesis that an increased calcium transient enhances an inward Na-Ca exchange current during late systole, and in the presence of an abbreviated action potential, serves as a basis for EADs and triggered arrhythmia. Using intracellular microelectrode recordings in superfused canine pulmonary vein sleeves, EADs were observed following NE administration (N= 18 of 23). EAD formation was pause-enhanced, following a single premature beat or a 5-20 beat (5.0 Hz) pacing train. Both EAD formation and triggered arrhythmia were suppressed by ryanodine administration (10 μM for 10 min), an intervention suppressing the calcium transient. EAD formation with pacing was enhanced by facilitation of Na-Ca exchange (forward mode)(reintroduction of 140 mM Nao following superfusion with 30 mM NaCl substituted with LiCl) and was suppressed by an acute increase in Cao from 1.35 to 5 mM, an intervention decreasing inward Na-Ca exchange. Triggering of rapid (¾800 bpm) sustained (¾1 sec in duration) arrhythmia was observed following acetylcholine administration in the presence of NE (N= 18 of 23).

Limited Benefit of Septal Pre‐Excitation in Pace Prevention of Atrial Fibrillation

Pre-excitation of the intra-atrial septum (IAS) by pacing at the ostium of the coronary sinus (CSO) can prevent atrial fibrillation (AF) in case of single atrial premature beats (APBs). We investigated whether pre-excitation of IAS, either by pacing at CSO or at the right ventricle in the presence of retrograde conduction (RV), can prevent atrial tachyarrhythmia triggered by single and multiple APBs. AF vulnerability was compared to pacing at the right atrium (RA) and sinus rhythm (SR). Seventeen patients, age 52 +/- 21 years, who exhibited retrograde VA conduction and reproducible induction of atrial tachyarrhythmia during an electrophysiological procedure, were studied. Both during SR and pacing (S1-S1:600 ms) at RA, CSO, and right ventricle (RV), single (A1-S2:200 ms) and multiple premature stimuli (A1-S2-S3-S4:200-180-180 ms) were delivered at RA (4 x diastolic threshold). During pacing at RA, single and multiple APBs invariably induced runs of atrial tachyarrhythmia (mean duration 34 +/- 67 sec and 37 +/- 69 sec, range 1 sec to 20 min). During preventive pacing at CSO and RV, single APBs (A1-S2:200 ms) did not induce atrial arrhythmia (0 +/- 0 sec, 0 +/- 0 sec, P < 0.05 vs pacing at RA). In contrast, when multiple APBs were applied, pacing at CSO or RV failed to prevent initiation of AF (mean duration 36 +/- 63 sec, 38 +/- 65 sec, NS). Also during SR, single APBs did not induce AF (0 +/- 0 sec, P < 0.05 vs pacing at RA) whereas multiple APBs invariably induced AF (39 +/- 74 sec, NS). Compared to pacing at RA, pre-excitation of IAS either by pacing at CSO or at RV with retrograde conduction can prevent initiation of paroxysms of atrial tachyarrhythmia triggered by single but not by multiple right APBs. These findings imply that the potential benefit of choosing an optimal pacing site in patients requiring atrial-based pacing is limited. Moreover, in the absence of bradycardia, no specific pacing site offers incremental benefit over the natural "protective" effect of sinus rhythm.

Is there an optimal pacing site to prevent atrial fibrillation?: an experimental study in the chronically instrumented goat.

Atrial pacing can reduce the number of recurrences of atrial fibrillation (AF). It is unclear the extent to which this effect is determined by the site(s) of pacing. In six electrically remodeled goats (24-hour AF), the window of inducibility of AF was determined by applying premature stimuli (S1-S2) at the right (RA) or left (LA) atrium (baseline values). Determination of the window of inducibility of AF at RA and LA was repeated during preventive pacing at four sites: RA, LA, Bachmann's bundle (BB), and RA+LA (biatrial). Mapping was used to elucidate the mechanisms of prevention of AF. At baseline, the window of inducibility of AF was 49 +/- 9 msec at RA and 45 +/- 17 msec at LA. Initiation of AF was associated with conduction block of the premature beat at BB. Preventive pacing at BB markedly shortened the window of inducibility of AF at RA (25 +/- 11 msec) and LA (17 +/- 8 msec, P < 0.01). Pacing at RA only shortened the window of inducibility of AF at LA (23 +/- 9 msec, P < 0.01), whereas pacing at LA only shortened the window of inducibility of AF at RA (23 +/- 11 msec, P < 0.01). Biatrial pacing failed to shorten the window of inducibility of AF both at RA and LA. Prevention of AF by pacing was due to prolongation of the premature interval at BB. In the caprine model of AF, BB is a critical area of conduction of premature beats and initiation of AF. Pacing at BB can prevent but not completely abolish the initiation of AF by single premature beats (shortening of the window of inducibility). Prevention of AF by pacing is based on prolongation of the premature interval at BB, thus preventing conduction block and reentry. In general, the optimal site for preventive pacing is close to the area of block and remote from the origin of premature beats.

Simulation and prediction of functional block in the presence of structural and ionic heterogeneity.

Inhomogeneities in myocardial structure and action potential duration (APD) lead to dispersion of APD throughout the heart. APD gradients in the range of 20-125 ms/cm have been reported to produce functional block. In this study, a multicellular fiber model was used to examine the effect of structural and ionic inhomogeneities on the likelihood of premature stimuli to produce functional block. With the use of both the Fenton-Karma and Luo-Rudy phase II membrane models, functional block is found to occur in tissue with a maximum gradient <45 ms/cm and depends on the spatial extent. In general, the narrower the extent the larger the magnitude needed for block. A simple relationship for predicting block is presented that only requires information about the conduction velocity (CV) restitution properties of the tissue and the APD gradients. Analysis reveals that the effects of a steep CV restitution slope may be beneficial in overcoming intrinsic cellular heterogeneity for a single premature beat.

Are electrophysiological changes induced by longer lasting atrial fibrillation reversible? :observations using the atrial defibrillator.

Studies in animal hearts have shown shortening of the atrial effective refractory period (AERP) and loss of the relation between the AERP and heart rate after prolonged periods of atrial fibrillation (AF). The purposes of this study were (1) to evaluate atrial electrophysiology after a long period of sinus rhythm in patients who had longer lasting recurrent AF that was successfully treated with the Metrix Atrioverter and (2) to analyze the effect of prompt cardioversion on subsequent AF episodes and the duration of sinus rhythm. Four patients with recurrent AF (duration, 3 to 21 years; mean+/-SD, 13+/-7.6 years) were studied after the implantation of an Atrioverter. The Atrioverter stores and analyzes 3 minutes of cardiac rhythm every hour. Before implantation, AERP was measured. During a mean follow-up of 14 months, 52 spontaneous (39 treated and 18 nontreated) AF episodes occurred while the patients were on antiarrhythmic drugs. All patients were electrophysiologically studied after they had been in sinus rhythm for at least 1000 hours (range, 1052 to 2675 hours). Before Atrioverter implantation, AF was induced by 1 atrial premature beat in 3 patients and not induced in the remaining patient. After a long period in sinus rhythm (>1000 hours), AF could be induced in the same 3 patients in the same way as before implantation. In the patient in whom no AF was induced, right AERP values measured using the single extrastimulus technique at 3 pacing cycle lengths (600, 500, and 430 ms) were similar to those before implantation. AF was still inducible by a single atrial premature beat after long episodes of sinus rhythm in 3 of 4 patients with previously longer lasting AF. In the patient in whom no AF was induced, AERP behaved like it did before implantation. In these patients with longer lasting recurrent AF, no return to "normal" atrial electrophysiology could be demonstrated.

Mechanism of arrhythmogenicity of the short–long cardiac sequence that precedes ventricular tachyarrhythmias in the long QT syndrome

OBJECTIVESThe purpose of this study was to investigate the electrophysiologic mechanism(s) that underlie the transition of one or more short–long (S-L) cardiac sequences to ventricular tachyarrhythmias (VTs) in the long QT syndrome.BACKGROUNDOne or more S-L cardiac cycles, usually the result of a ventricular bigeminal rhythm, frequently precedes the onset of VT in patients with either normal or prolonged QT interval. Electrophysiologic mechanisms that underlie this relationship have not been fully explained.METHODSWe investigated electrophysiologic changes associated with the transition of a S-L cardiac sequence to VT in the canine anthopleurin-A model, a surrogate of LQT3. Experiments were performed on 12 mongrel puppies after administration of anthopleurin-A. Correlation of tridimensional activation and repolarization patterns was obtained from up to 384 electrograms. Activation–recovery intervals were measured from unipolar electrograms and were considered to represent local repolarization.RESULTSWe analyzed 24 different episodes of a S-L sequence that preceded VT obtained from 12 experiments. The VT followed one S-L sequence (five episodes), two to five S-L sequences (12 episodes) and more than five S-L sequences (seven episodes). The single premature ventricular beats coupled to the basic beats were consistently due to a subendocardial focal activity (SFA). There were two basic mechanisms for the development of VT after one or more S-L sequences: 1) in 10 examples of a S-L sequence due to a stable unifocal bigeminal rhythm, the occurrence of a second SFA, which arose consistently from a different site, infringed on the pattern of dispersion of repolarization (DR) of the first SFA to initiate reentrant excitation; 2) in the remaining 14 episodes of a S-L sequence, a slight lengthening (50 to 150 ms) in one or more preceding cycle lengths (CLs) resulted in alterations of the spatial pattern of DR at key sites to promote reentry. The lengthening of the preceding CL produced differentially a greater degree of prolongation of repolarization at midmyocardial and endocardial sites compared with epicardial sites with consequent increase of DR. The increased DR at key adjacent sites resulted in the development of de novo zones of functional conduction block and/or slowed conduction to create the necessary prerequisites for successful reentry.CONCLUSIONSThe occurrence of VT after one or more S-L cardiac sequences was due to well defined electrophysiologic changes with predictable consequences that promoted reentrant excitation.

Use of a multielectrode “basket” catheter for endocardial mapping of ventricular tachycardia

Successful ablation of sustained ventricular tachycardia (VT) following myocardial infarction (MI) depends on an accurate analysis of the arrhythmic substrate. A post-MI porcine model of sustained VT was created by injecting agarose gel beads (75–150 μm) into the mid-left anterior descending coronary artery following percutaneous transluminal coronary angiographic balloon occlusion in 96 animals. When animals returned for induction and analysis of VT 4–6 weeks post-MI, VT could be induced in 42–61 (68%) of surviving animals; VT cycle length was 179 ± 25 ms at baseline and 230 ± 43 ms following intravenous procainamide ( P < .001). Endocardial mapping using a multielectrode “basket” catheter (Constellation, EP Technologies, Sunnyvale CA) was performed in 38 animals. The catheter consists of 64 electrodes symmetrically arranged on eight self-expanding struts. Unipolar pacing was successful from 78 ± 15% of the electrodes at 3 mA and from an additional 13 ± 7% at 10 mA. Ventricular tachycardia activation mapping obtained from 32 bipolar pairs recorded earliest ventricular activity 40 ± 23 ms prior to QRS onset. Isolated mid-diastolic potentials were recorded from 26 animals. Further analysis demonstrated reset response with single premature beats in 6 of 12 classic entrainment in 19, and concealed entrainment in 10. Radiofrequency (RF) ablation was attempted in 12 animals. Target sites for RF ablation of VT were guided by the results of mapping with the basket catheter, which pointed to a zone of slow conduction. The RF energy was delivered to the tip of an 8-mm ablation probe directed to the target site by a custom discrete navigation device, which assessed electrode orientation. Power was regulated to maintain a tip temperature of 70–80°C for 60 seconds. Ablation was successful in terminating VT and preventing reinduction of the target VT in 11 of 12 animals. It was concluded that multielectrode basket catheter assists in the rapid analysis of sustained VT following MI and provides important data for successful ablation.

Right ventricular cardiomyopathy: diffuse dilatation, focal dysplasia or biventricular disease

Non-coronary ventricular tachyarrhythmias originating from the right ventricle are frequent events associated in many cases with structural and functional abnormalities of the right ventricle. Primary right ventricular affections such as arrhythmogenic right ventricular dysplasia and secondary right ventricular involvements such as in dilated cardiomyopathy must be distinguished. The value of conventional diagnostic procedures is undetermined. A total of 73 patients (41 males, mean age 40.6±11.4 years) with left bundle branch block ventricular arrhythmias and angiographic aspects of right ventricular outpouchings or aneurysms were divided into three groups: Group 1: diffuse right ventricular dilatation without left ventricular affection, Group 2: focal right ventricular abnormalities (dysplasia) Group 3: biventricular disease. The results of standard ECG, angiography and programmed ventricular stimulation were analysed retrospectively. Clinical monomorphic ventricular tachycardia was more often in diffuse dilatation (82%) and focal dysplasia (57%). In these two groups programmed ventricular stimulation was able to induce clinical tachycardias at a high degree (57–82%). In cases of biventricular disease cardiac arrest as the primary event without inducibility of monomorphic ventricular tachycardia was the predominant feature (44%). Standard ECG disclosed localised right precordial QRS prolongation in `normal' QRS morphology, incomplete and complete right bundle branch block in 66 patients in all three subgroups. Other ECG findings such as left ventricular hypertrophy in four patients with heart failure and single premature beats and left bundle branch block in a patient with rapid ventricular tachycardia and ventricular fibrillation was found only in group 3 supposed to be the most heterogeneous group. In summary, angiographic classification used in this study demonstrates different morphological aspects of right ventricular cardiomyopathy with ventricular tachyarrhythmias as the major clinical aspect. High risk patients with diffuse dilatation or biventricular disease can be identified. Only patients with the angiographic aspect of focal dysplasia seem to be possible candidates for catheter ablation techniques.

977-75 Variations in the Termination of Atrial Flutter by Premature Beats. Studies in the Sterile Pericarditis Model

Variations and incidence of atrial flutter (AFL) termination by single premature beats were evaluated in 26 dogs of the sterile pericarditis model. Single premature beats were introduced during stable AFL at 4 different sites in the AFL reentrant circuit, 2 at areas of slow conduction (ASC sites) and 2 at sites distant from the ASC (distant sites). The coupling interval of delivered premature beats was decremented by 2 ms from the AFL cycle length until AFL termination or local refractoriness was achieved. A multiplexing system was used to record 190 unipolar electrograms from an electrode array placed on the right atrial free wall during AFL. AFL was interrupted by a single premature beat in 38/52 episodes when pacing at distant sites, and in 7/52 episodes when pacing at ASC sites (p &lt; 0.0001). AFL termination was always associated with block of the activation wave front of the premature beat in an ASC. Of the 38 episodes of AFL termination by a premature beat introduced at distant sites, sinus rhythm directly followed in 27 episodes (71%), and an extra non AFL reentrant beat proceded sinus rhythm in 8 episodes (21%). In these 35 episodes (92%), block of the activation wave front of the premature beat was always total block, and no degeneration in the reentrant circuit was observed. In the remaining 3/38 episodes (8%), block of the activation wave front of the premature beat in an ASC was partial block, so that the central line of block of the reentrant circuit was prolonged, resulting in degeneration of the reentrant circuit. Of the 7 episodes of AFL termination by a premature beat introduced at ASC sites, sinus rhythm directly followed in all episodes (100%). In the canine sterile model of AFL: 1) AFL termination by single premature beats was always associated with block of the activation wave front of the premature beat in an ASC; 2) a higher incidence of AFL termination by single premature beats was achieved at distant sites than ASC sites, indicating that not only the coupling interval of the premature beat, but also the direction of the activation wave front plays an important role to cause block in an ASC; 3) AFL termination directly followed by sinus rhythm was most commonly observed during AFL termination by a premature beat; and 4) degeneration in the AFL reentrant circuit associated with an introduction of premature beat was observed in only 8% when paced at distant sites, and 0% when paced at ASC sites.

Premature beats elicit a phase reversal of mechanoelectrical alternans in cat ventricular myocytes. A possible mechanism for reentrant arrhythmias.

Alternans of the ST segment of the ECG is an important risk factor for sudden cardiac death. Premature beats during alternans and the development of discordant alternans are associated with the onset of ventricular tachycardia and ventricular fibrillation. Moreover, premature beats can switch the pattern of alternans from discordant to concordant alternans. The mechanisms of how a premature beat can elicit a pattern shift in alternans and develop malignant ventricular arrhythmias are not clear. The purpose of this cellular study was to determine the electrical and mechanical restitution properties during cycle length-induced alternans and to determine how premature and delayed beats affect the resultant phase of alternans. A perforated patch recording method and video-based edge detector were used to record action potentials and contractions, respectively, from single ventricular myocytes enzymatically isolated from the cat heart. Electrical and mechanical restitution curves were determined by programmed test beats delivered at different cycle lengths during mechanoelectrical alternans. At 35 degrees C, 97.8% of cells exhibited concordant cellular alternans (action potentials with the larger action potential duration [APD] were associated with the larger contraction, and action potentials with the smaller APD exhibited the smaller contraction). The sequence or phase of concordant cellular alternans could be systematically reversed by (1) early premature beats that followed only action potentials with the shorter APD and smaller contraction (type 1 phase reversal; n = 34) or (2) late delayed beats that followed only action potentials with the longer duration and the larger contraction (type 2 phase reversal; n = 14). A phase reversal point was defined as a threshold time interval that resulted in switching the sequence of the alternating beats. A test stimulus at the phase reversal point caused temporary suppression of mechanoelectrical alternans. Lower temperatures (32 degrees C) or decreases in the basic cycle length induced larger beat-to-beat changes in the magnitude of alternans (APD or contraction) and significantly shifted the phase reversal point to earlier premature intervals for type 1 phase reversal. The interval of the phase reversal point was a function of the contractile ratio (the magnitude of the larger contraction/smaller contraction for two consecutive beats, r = .93) and not the APD ratio (longer APD/shorter APD; r = .501). In cells stimulated at cycle lengths longer than the threshold of alternans, a single premature beat could elicit a damped form of concordant mechanoelectrical alternans. A critically timed second premature beat reversed the phase of the damped alternans. Properly timed premature or delayed beats during cycle length-induced alternans consistently reversed the phase of cellular mechanoelectrical alternans. Reversal of the phase of alternans was dependent on recovery of mechanical activity, not electrical activity. The premature stimulus interval at the phase reversal point can be predicted by the magnitude of mechanical alternans. Thus, during cycle length-induced alternans, mechanical alternans governs the phase of electrical alternans. From the present results, a multi-cellular model is proposed that may explain how critically timed premature beats cause a regional change in the phase of mechanical alternans and thereby result in discordant electrical alternans or dispersion of refractoriness. Premature beats that induce phase reversal in mechanoelectrical alternans may contribute to the development of reentrant arrhythmias.

Subthreshold stimulation of Purkinje fibers interrupts ventricular tachycardia in intact hearts. Experimental study with voltage-sensitive dyes and imaging techniques.

The effects of subthreshold stimulation (STS) delivered during right atrial pacing and ventricular tachycardia (VT) were investigated in Langendorff-perfused guinea pig hearts. The hearts were stained with a voltage-sensitive dye (RH 421) to map the propagation of optical action potentials. Sustained VT was reliably induced by 5-second trains (cycle length [CL], 25 to 50 milliseconds; duration, 0.5 to 10 milliseconds; and voltage, 2x threshold voltage) of impulses (n = 12 hearts) or a single premature beat (n = 6). The location of extrastimuli was not critical to the induction of VT, but the diameter of the heart had to be > or = 14.5 mm. During VT, heart rate increased from 200 to 600 beats per minute; action potential durations decreased from 112 to 175 milliseconds to 60 to 105 milliseconds, with no diastolic interval. Activation on the epicardium spread anisotropically, but VT decreased the "apparent" maximum conduction velocity (theta max) by 68% and altered the orientation of the major axis from beat to beat. Activation patterns and theta max measured during VT were similar to patterns recorded during direct pacing of the ventricle and indicated that Purkinje fibers no longer propelled ventricular excitation. STS (CL, 25 to 50 milliseconds; duration, 0.5 to 25 milliseconds; and voltage, 0.5x to 0.8x threshold; trains of 2.0 to 2.5 seconds) interrupted VT when applied to Purkinje fibers lining the endocardium (n = 6) but failed to interrupt VT when applied to the epicardium (n = 8). In atrial pacing, STS delivered to the endocardium increased theta max from 2.44 +/- 0.32 (mean +/- SEM) to 3.63 +/- 0.21 m/s in a local region surrounding the first activation sites (n = 4). Alternatively, VT could be terminated by reducing theta max (approximately 55%) with procainamide (10 mumol/L) (n = 6). STS terminates VT by synchronizing ventricular excitation most likely by increasing local conduction and/or improving the coupling between Purkinje and ventricular cells.

Interaction of acute ventricular dilatation and d-sotalol during sustained reentrant ventricular tachycardia around a fixed obstacle.

Antiarrhythmic therapy of ventricular tachycardia is associated with decreased efficacy and increased proarrhythmia in patients with congestive heart failure, but the explanation for these observations is not known. This study examined the interaction of ventricular dilatation and d-sotalol in a model of reentry ventricular tachycardia. Thin epicardial layers of anisotropic myocardium were created in Langendorff-perfused rabbit left ventricles by a cryo procedure. A fluid-filled, latex balloon was secured within the left ventricle to change ventricular volume. Sustained reentrant ventricular tachycardia, around a central cryolesion, was induced by rapid pacing in all preparations (n = 7). Epicardial mapping was performed through 248 electrodes. Single premature beats introduced within the reentry circuit were used to define the excitable gap. Dilatation did not influence ventricular tachycardia cycle length or conduction velocity. A 1.25-mL increase in left ventricular volume widened the excitable gap by 12% (range, 5% to 29%) (P < .001) because of a decrease in myocardial refractoriness. d-Sotalol (final concentration, 10 mg/L) narrowed the excitable gap 18% (range, 7% to 29%) (P = .002) in the undilated left ventricle. d-Sotalol was less effective in the dilated left ventricle, narrowing the excitable gap only 9%, a difference that was not statistically significant. During pacing to induce or terminate tachycardia, tachycardia acceleration was observed significantly more frequently in the dilated than in the undilated ventricle. Ventricular tachycardia acceleration was due to the development of double-wave reentry (two successive waves traveling in the same circuit in the same direction). d-Sotalol, which narrowed the excitable gap, prevented tachycardia acceleration and double-wave reentry. Antiarrhythmic efficacy may be decreased by dilatation because of widening of the initial excitable gap and a decrease in the gap-narrowing effect of these agents. Double-wave reentry, more likely with a widening of excitable gap, may partially explain tachycardia acceleration in the dilated ventricle.

Propagation of Electrical Activity in Ischemic and Infarcted Myocardium as the Basis of Ventricular Arrhythmias

Impulse Propagation in Ischemia. The disturbances in impulse propagation in the heart with regional ischemia and the heart with chronic infarction, which underlie the initiation and perpetuation of arrhythmias, are briefly reviewed. Evidence is presented that reentry is responsible for ventricular tachycardia in both conditions. During acute ischemia, reentrant excitation is characterized by unstable functional reentrant circuits, the properties of which are determined by the changes in transmembrane action potential. Tachycardia is caused by a single unstable reentrant circuit. Fibrillation ensues when a single circuit is broken up into many independent reentrant wavelets. In contrast, ventricular excitation during sustained monomorphic tachycardia in hearts with a healed infarct is characterized by stable reentrant circuits determined by the architecture of surviving myocardial cell bundles within the infarct. In acutely ischemic myocardium, conduction velocity is reduced to about half of the value in normal myocardium, due to the reduced action potential amplitude and upstroke velocity. After about 5–10 minutes ischemic cells become inexcitable at resting membrane potentials of ‐50 to ‐60 mV. An important characteristic of ischemic cells is the dependence of the action potential upstroke on cycle length mainly because of the markedly prolonged recovery from inactivation of the fast Na+ current in partially depolarized cells. Changes in transmembrane potentials do not occur homogeneously throughout the ischemic zone, and small differences in resting potential (associated with small differences in local K+ accumulation) of depolarized cells result in large local differences in refractory periods. The time dependence of refractoriness explains why an increase in sinus rate, or a single premature beat, may produce conduction block at certain sites, and allow conduction in adjacent areas, thus setting the stage for reentry. A decrease in electrical cell‐to‐cell coupling, which also is a factor in decreasing conduction velocity, only occurs after 15–20 minutes of ischemia. Its role in the type 1B arrhythmias, which coincide with the period when uncoupling begins, remains to be elucidated. The cellular electrophysiology of myocardial cells surviving in the subendocardium of infarcts in human hearts is close to normal. Conduction slowing may be caused by “zigzag” conduction along small bundles that are separated by fibrous tissue, and that merge and divide over small distances. (J Cardiovasc Electrophysiol, Vol. 3, pp. 77–87, February 1992)

Quantitation of dynamic AV nodal properties and application to predict rate-dependent AV conduction

A number of functional properties of the atrioventricular (AV) node have been described in response to changes in the atrial input rate. The purpose of this study was 1) to develop quantitative descriptors of these properties, and 2) to determine whether they can account for rate-dependent changes in AV nodal conduction. The delay in AV nodal conduction of single premature beats (recovery) was found to be an exponential function of coupling interval with a time constant of 66 +/- 2 (+/- SE) ms. A single abbreviated (facilitation) cycle did not alter the time constant of recovery or basal conduction for a subsequent beat but shifted its recovery curve to the left to an extent exponentially related to the facilitation cycle length. The induction of a tachycardia with HA interval fixed so as to control the recovery and facilitation variables resulted in a first-order onset of AV conduction slowing (fatigue). The fatigue process had a time constant in the range of 70 beats and a magnitude that was a decaying exponential function of HA interval. An equation incorporating quantitative descriptors of recovery, facilitation, and fatigue accurately predicted rate-dependent changes in AH interval. We conclude that 1) the AV nodal properties of recovery, facilitation, and fatigue are amenable to quantitative characterization, and 2) rate-dependent changes in AV nodal conduction time can be well described in terms of these underlying properties.

Manifest Fast and Slow Pathway Conduction Patterns and Reentry in a Patient with Dual AV Nodal Physiology

Manifest Fast and Slow AV Nodal Conduction Patterns and Reentry. A 52‐year‐old woman with paroxysmal supraventricular tachycardias (PST) showed short and long PR intervals during sinus rhythm. Repetitive episodes of PST due to simultaneous anterograde conduction through fast and slow conduction pathways (one P‐two QRS) were recorded. A self‐limited episode of non‐paroxysmal AV nodal reentry with anterograde slow and retrograde fast pathway conduction was initiated by a single atrial premature beat. Each pathway depicted distinct refractory periods, conduction velocities, unidirectional block, and Wenckebach‐type block suggesting the possibility of a well‐defined anatomical substratum.

Enhancement of sympathetic nerve activity by single premature ventricular beats in humans

This is the first systematic study of the effects of ventricular premature beats on sympathetic nerve activity in humans. Microneurographic techniques were used to record efferent sympathetic activity from the peroneal nerve, and an intracardiac electrode catheter was used to introduce ventricular premature beats after every 6 to 10 sinus heartbeats. Studies were performed in eight patients, aged 22 to 74 years (mean 57), undergoing cardiac electrophysiologic studies. Three patients did not have apparent heart disease and five had coronary artery disease.During sinus rhythm, 19 to 93% (mean 42%) of heartbeats were followed by a pulse-synchronous burst of sympathetic activity. Provoked ventricular premature beats had obvious effects on this activity. Premature beats with coupling intervals <80% of sinus cycle length were consistently followed by a burst of sympathetic activity, and this activity was greater in amplitude, duration and area (all p < 0.05) than were bursts of such activity during sinus rhythm. The magnitude of this burst of activity increased as the coupling interval of the ventricular premature beat decreased (p < 0.0001). In contrast, postextrasystolic beats were followed by nearly complete neural silence. These effects were seen in all patients regardless of baseline burst incidence and the presence or absence of heart disease. Total nerve activity per 10 heartbeats was 6,520 ± 770 U during ventricular extrastimulation and 5,720 ± 440 U during normal sinus rhythm (difference not significant).It is concluded that single ventricular premature beats provoke fluxes of muscle sympathetic nerve activity in humans, comprising surges of sympathetic activity larger than those occurring during sinus rhythm, followed by neural silence.

Modification of the DDD Pacing Mode to Prevent Junctional Reentry Tachycardia: Computer Modelling Experiments

This paper examines the possibility of using short atrioventricular (AV) delay dual chamber pacing to prevent junctional reentry tachycardia mediated by an accessory pathway or by an intra-AV nodal circuit. For this purpose, a clinically realistic computer simulation model of cardiac rhythm and heart-pacemaker interactions has been used. The computational experiments compared the actions of two pacemaker models: (A) a clinically realistic DDD mode operating with quasi-Wenckebach prolongation of the AV delay; and (B) a new modification of the DDD mode introducing independent counters for the atrial and ventricular refractory periods of the heart, and the possibility of instantaneous or shortly delayed atrial pacing triggered by a sensed or paced ventricular event. The pathological phenomena modelled in the experiments simulate different possibilities of tachycardia initiation. These disorders include: (1) single atrial premature beats (APBs), (2) salvos of APBs, (3) closely coupled pairs of APBs, (4) ventricular premature beats initiating an antidromic reentry tachycardia, and (5) ventricular ectopic beats initiating an AV nodal reentry tachycardia. The computational results prove that many possible mechanisms of initiation of junctional reentry tachycardia are beyond the prophylactic capabilities of current sophisticated DDD pacemakers (A). The results also show that the suggested pacing mode (B) improves anti-tachycardia prophylaxis even when responding to complex pathological episodes of the natural cardiac activity. Future development of the suggested mode (B) is discussed.

Prediction of efficacy and tolerance of oral mexiletine by intravenous lidocaine application.

In a controlled crossover trial, 15 patients with frequent ventricular arrhythmias were treated with lidocaine to predict efficacy and safety of oral mexiletine. After an initial control period, patients received intravenous lidocaine (bolus infusion of 200 mg/20 min followed by 3.6 gm/24 hr and for 7 days oral mexiletine (200 mg four times a day). Efficacy was controlled by 24-hour Holter monitoring (responders = suppression of single premature ventricular beats [PVB] greater than 84% and of complex PVB greater than 90%). After lidocaine, 10 of 15 patients (67%) were responders (mean PVB reduction: 97%). After mexiletine, five of 15 patients (33%) were responders (mean PVB reduction: 81%); efficacy was closely related to the plasma concentration. When efficacy of both agents was compared, lidocaine infusion had a positive predictive value of only 50%; however, the negative predictive value was 100%. Thus in nonresponders to lidocaine, mexiletine is very likely to fail in the suppression of ventricular ectopy.

Controlled atrial fibrillation and a possible mechanism of its origin

In experiments on cats a single premature beat or vagal stimulation shortened the effective refractory period without any spontaneous heart rate disturbances, while the combined action of these factors always led to paroxysmal tachycardia or atrial fibrillation. It is suggested that contracting myocardium possesses a covert ability for self-excitation revealed only in critical shortening of the action potential. Since the excitation occurring in such conditions is also a premature beat, the fibrillation process becomes self-maintaining.

Continuous ECG monitoring of children with cancer receiving domperidone.

Domperidone is an effective antiemetic for children receiving cytotoxic therapy. There have been reports of cardiac arrest in older patients associated with domperidone. We carried out continuous ECG monitoring of 18 children receiving domperidone intravenously in a dose of 1 mg/kg body weight. No serious dysrhythmias were noted during 379 h of recording. Single premature beats, transient sinus pauses, and nodal block were occasionally associated with vomiting and were no more common than would be expected in a population of normal children.