His bundle pacing shows similar ventricular electrical activation as sinus: selective and nonselective His pacing indistinguishable.

His bundle pacing utilizes the His-Purkinje system to produce more physiological activation compared with traditional pacing therapies, but differences in electrical activation between pacing techniques are not yet quantified in terms of activation pattern. Furthermore, clinicians distinguish between selective and nonselective His pacing, but measurable differences in electrical activation remain to be seen. Hearts isolated from seven dogs were perfused using the Langendorff method. Electrograms were recorded using two 64-electrode basket catheters in the ventricles and a 128-electrode sock situated around the ventricles during sinus rhythm (right atrial pacing), right ventricular (RV) pacing, biventricular cardiac resynchronization therapy (biV-CRT), selective His pacing (selective capture of the His bundle), and nonselective His pacing (capture of nearby myocardium and His bundle). Activation maps were generated from these electrograms. Total activation time (TAT) was measured from the activation maps, and QRS duration was measured from a one-lead pseudo-ECG. Results showed that TAT, QRS duration, and activation sequence were most similar between sinus, selective, and nonselective His pacing. Bland-Altman analyses showed highest levels of similarity between all combinations of sinus, selective, and nonselective His pacing. RV and biV-CRT activation patterns were distinct from sinus and had significantly longer TAT and QRS duration. Cumulative activation graphs were most similar between sinus, selective, and nonselective His pacing. In conclusion, selective pacing and nonselective His bundle pacing are more similar to sinus compared with RV and biV-CRT pacing. Furthermore, selective pacing and nonselective His bundle pacing are not significantly different electrically.NEW & NOTEWORTHY Our high-density epicardial and endocardial electrical mapping study demonstrated that selective pacing and nonselective His bundle pacing are more electrically similar to sinus rhythm compared with right ventricular and biventricular cardiac resynchronization therapy pacing. Furthermore, small differences between selective and nonselective His bundle pacing, specifically a wider QRS in nonselective His pacing, do not translate into significant differences in the global activation pattern.

Electrophysiological parameters and anatomical evaluation of left bundle branch pacing in an in vivo canine model.

INTRODUCTION: Left bundle branch pacing (LBBP), a form of conduction system pacing in addition to His bundle pacing (HBP), can potentially maintain left ventricular electrical synchrony with better sensing and a low and stable capture threshold. METHODS: We performed both HBP and LBBP using a canine model (n = 3; male; weight 30-40 kg). The electrocardiogram (ECG), intracardiac electrogram characteristics, and pacing parameters were compared between HBP and LBBP. The hearts were isolated and stained by Lugol's iodine (5%) to assess the relative locations of the leads in relation to the conduction system. RESULTS: The average potential to ventricle interval was longer with HBP compared to LBBP (26.67 ± 3.06 ms vs 12.67 ± 1.15 ms; P = .002). There were also notable differences in the pacing parameters between HBP and LBBP: R-wave amplitude (2.67 ± 0.42 mV vs 11.33 ± 3.06 mV; P = .008), pacing impedance (423.3 ± 40.4 vs 660.0 ± 45.8; P = .003), and threshold (2.30 ± 0.66 V/0.4ms vs 0.67 ± 0.15 V/0.4 ms; P = .014). The paced morphology of ECG was similar to the intrinsic with HBP while a right bundle branch block pattern was noted with LBBP. The anatomical evaluation revealed the location of the leads and the average lead depth was significantly more with LBBP as compared to HBP (12.33 ± 1.53 mm vs1.83 ± 0.29 mm; P < .0001). Furthermore, with LBBP, the tip of the lead helix was noted to be around the LBB. CONCLUSION: This in vivo canine model study confirms the significant differences between HBP and LBBP. Furthermore, this model provides a precise anatomic evaluation of the location and the depth of the leads in relation to the conduction system.

Noninvasive Determination of HV Interval Using Magnetocardiography.

BACKGROUND: The His-ventricular (HV) interval is an important index of atrioventricular conduction, but at present can be reliably measured only during an invasive electrophysiology (EP) study. Magnetocardiography (MCG) is a noninvasive measurement of weak magnetic fields generated by the heart. We compared HV interval noninvasively assessed using MCG with the corresponding values measured directly in an EP study. METHODS: MCG was measured using a 37-channel system inside a magnetically shielded room in patients who had previously undergone an EP study. His-bundle potential was identified in the PR segment after signal averaging. Magnetic field maps representing the spatial distribution of ramp-like signals in the PR segment generated at various instants of time were used to identify His-bundle signals in cases where the deflection representing the His was ambiguous. RESULTS: The study included 23 patients (14 male, nine female) with a wide range of HV intervals measured during EP study (49 ± 17 ms, range 35-120 ms). In 21 (91%) subjects, discernible His-bundle signals are observed in the PR segment of MCG traces. HV intervals measured between the two methods showed a correlation (r2 = 0.87, P < 0.0001) with a mean difference of 5.4 ± 3.2 ms. CONCLUSION: With the use of new criteria to identify the His-bundle deflection in signal-averaged MCG signals, we report a high success rate in noninvasive HV interval measurement and a good agreement with those from EP study. The results encourage the use of MCG as a noninvasive method for measurement of the HV interval.

Human His-Purkinje System: Normal Electrophysiologic Behavior.

The His-Purkinje system (HPS) plays a significant role in human pathophysiology, but knowledge is scattered. This article highlights some of the relevant concepts, phenomena, and mechanisms; clarifies, expands, confirms, or modifies commonly encountered clinical events; and adds new information, which is often available but obscure. Also included are the essentials of HPS anatomy and physiology. It is important to abandon inaccurate concepts that are still taught and occasionally appear in text books.

In vivo recording of Zhang's phenomenon (His electrogram alternans): a novel index of atrioventricular node dual pathway conduction.

BACKGROUND: Zhang's phenomenon (originally His electrogram alternans) is a new index of atrioventricular node dual pathway electrophysiology. This index has been described and validated in isolated hearts in vitro, but has not been recorded in vivo. METHODS: This study explored the feasibility of in vivo recording of Zhang's phenomenon (His electrogram alternans) in six dogs with a custom-built bipolar electrode. RESULTS: The His electrogram recorded from superior His bundle domain (superior His electrogram) was high in amplitude at basic beats and long coupling intervals (i.e., fast pathway conduction) and low amplitude at short prematurities (i.e., slow pathway conduction). In contrast, His electrogram recorded from the inferior His bundle domain (inferior His electrogram) was always from low amplitude during fast pathway conduction to high amplitude during slow pathway conduction. The characteristic His electrogram alternans had been recorded in vivo in all six animals. CONCLUSIONS: This study provided the first data representing in vivo recording of Zhang's phenomenon (His electrogram alternans) in large animals. Clinical studies are needed before this novel index can be applied in patients.

Alternative endocardial sites for artificial cardiac stimulation.

The conventional right ventricular stimulation can be associated with deleterious effects on cardiac function. The need for a more physiological artificial cardiac stimulation is undoubtedly one of the most important points in the area of cardiac electrotherapy. The programming algorithms for the maintenance of adequate atrioventricular conduction, the stimulation of alternative endocardial sites and the cardiac resynchronization therapy are used with the objective of attaining these goals. The stimulation of the bundle of His and the septal stimulation have been studied as alternative endocardial sites for the positioning of the electrode on the right ventricle. The septal stimulation represents a simple and practical alternative, with no additional costs involved and with potential benefits in decreasing the deleterious effects of the right ventricular stimulation. However, this alternative site involves a heterogeneous group of patients and presents conflicting results regarding its long-term clinical benefit. This article reviews the scientific evidence on the alternative sites for right ventricular stimulation, with emphasis on the safety of the procedure, the measurement of the electrophysiological parameters, assessment of the left ventricular function and the clinical follow-up of patients.

Sítios endocárdicos alternativos na estimulação cardíaca artificial / Alternative endocardial sites for artificial cardiac stimulation / Sitios endocárdicos alternativos en la estimulación cardíaca artificial

A estimulação ventricular direita convencional pode estar associada a efeitos deletérios sobre a função cardíaca. A necessidade de uma estimulação cardíaca artificial mais fisiológica é, indiscutivelmente, um dos pontos mais importantes na área da eletroterapia cardíaca. Os algoritmos de programação para a manutenção da condução atrioventricular própria, a estimulação de sítios endocárdicos alternativos e a terapia de ressincronização cardíaca são utilizados com o intuito de alcançar este objetivo. A estimulação do feixe de His e a estimulação septal têm sido estudadas como sítios endocárdicos alternativos para o posicionamento do eletrodo no ventrículo direito. A estimulação septal representa uma alternativa simples, prática e sem custos adicionais e com potenciais benefícios na redução dos efeitos deletérios da estimulação do ventrículo direito. Entretanto, esse sítio alternativo envolve um grupo heterogêneo de pacientes e apresenta resultados conflitantes quanto ao seu benefício clínico a longo prazo. Este artigo faz uma revisão das evidências científicas sobre os sítios alternativos de estimulação ventricular direita, com ênfase na segurança do procedimento, na medida dos parâmetros eletrofisiológicos, na avaliação da função ventricular esquerda e no acompanhamento clínico dos pacientes.

The conventional right ventricular stimulation can be associated with deleterious effects on cardiac function. The need for a more physiological artificial cardiac stimulation is undoubtedly one of the most important points in the area of cardiac electrotherapy. The programming algorithms for the maintenance of adequate atrioventricular conduction, the stimulation of alternative endocardial sites and the cardiac resynchronization therapy are used with the objective of attaining these goals. The stimulation of the bundle of His and the septal stimulation have been studied as alternative endocardial sites for the positioning of the electrode on the right ventricle. The septal stimulation represents a simple and practical alternative, with no additional costs involved and with potential benefits in decreasing the deleterious effects of the right ventricular stimulation. However, this alternative site involves a heterogeneous group of patients and presents conflicting results regarding its long-term clinical benefit. This article reviews the scientific evidence on the alternative sites for right ventricular stimulation, with emphasis on the safety of the procedure, the measurement of the electrophysiological parameters, assessment of the left ventricular function and the clinical follow-up of patients.

La estimulación ventricular derecha convencional puede estar asociada a efectos deletéreos sobre la función cardíaca. La necesidad de una estimulación cardíaca artificial más fisiológica es, indiscutiblemente, uno de los puntos más importantes en el área de la electroterapia cardíaca. Los algoritmos de programación para la manutención de la conducción atrioventricular propia, la estimulación de sitios endocárdicos alternativos y la terapia de resincronización cardíaca son utilizados con el propósito de alcanzar este objetivo. La estimulación del haz de His y la estimulación septal han sido estudiadas como sitios endocárdicos alternativos para el posicionamiento del electrodo en el ventrículo derecho. La estimulación septal representa una alternativa simple, práctica y sin costos adicionales y con potenciales beneficios en la reducción de los efectos deletéreos de la estimulación del ventrículo derecho. Entre tanto, ese sitio alternativo envuelve un grupo heterogéneo de pacientes y presenta resultados conflictivos en cuanto a su beneficio clínico a largo plazo. Este artículo hace una revisión de las evidencias científicas sobre los sitios alternativos de estimulación ventricular derecha, con énfasis en la seguridad del procedimiento, en la medida de los parámetros electrofisiológicos, en la evaluación de la función ventricular izquierda y en el control clínico de los pacientes.

Comparison of different approaches for optimization of atrioventricular and interventricular delay in biventricular pacing.

AIMS: It has been shown that optimizing atrioventricular (AV) and interventricular (VV) delay improves cardiac performance in patients with biventricular pacemakers. However, there is no standard method for optimization available yet. The aim of this study was to compare echocardiographic parameters-displacement imaging, A wave duration, and aortic velocity time integral (VTI)-and acoustic cardiography derived electromechanical activation time (EMAT) using different approaches of AV and VV delay optimization. We tested whether the initial optimization of the AV interval followed by VV optimization at that optimal AV interval or initial optimization of the VV interval followed by AV optimization at the determined optimal VV interval was accurate and consistent, and how this compared to testing every conceivable combination of AV and VV intervals available. METHODS AND RESULTS: A group of 20 patients with biventricular pacemakers was included. Displacement imaging, A wave duration, and aortic VTI were determined at different combinations of AV (100, 150, 200, 250 ms) and VV (RV40, 0, LV40 ms) intervals. If AV duration was determined first, displacement imaging identified the best setting in 8/20, aortic VTI in 10/20, A duration in 13/20, and EMAT in 18/20 patients. With VV duration determined first, the best setting was more difficult to identify regardless of the method used. There was a poor agreement in optimal AV and VV delays of the different methods, and there was no single patient in whom all four methods yielded the same delay combination. CONCLUSION: It is advisable to measure a full grid of AV and VV delays to identify optimal settings rather than optimizing one of the two delays first. Different techniques for delay optimization resulted in different optimal delay combinations.

Unified rate-dependent atrioventricular nodal function: consistent recovery and fatigue properties revealed with S1S2S3 protocols and different recovery indexes.

BACKGROUND: Rate-dependent nodal properties are commonly assessed with premature protocols performed at different basic rates. Because characteristics of responses differ with recovery time index, the true nature of nodal rate-dependent properties is elusive. OBJECTIVES: The purpose of this study was to reveal consistent nodal rate-dependent properties regardless of selected recovery index. METHODS: With S(1)S(2)S(3) protocols, we independently varied basic and pretest cycle lengths and thereby distinguished cumulative from noncumulative effects of rate on nodal conduction time in rabbit heart preparations. Nodal responses to 30 basic and pretest cycle length combinations (five with identical basic and pretest cycles as in standard protocols) were analyzed using both atrial (AA) and His-atrial (HA) intervals as recovery index. RESULTS: AA and HA curves had an identical shape for any of 30 steady-state conditions. When assessed with constant pretest cycle lengths, cumulative effects (fatigue) of shortened basic cycle lengths were also independent of recovery index. Shortening of pretest cycle length at fixed basic rates led to apparent inhibitory and facilitatory effects when assessed with AA and HA curves, respectively. These effects vanished when a single long cycle was inserted after the pretest cycle. In all responses including those obtained with standard protocols, combined effects of basic and pretest cycle lengths set nodal conduction time. CONCLUSION: S(1)S(2)S(3) protocols reveal consistent nodal recovery and fatigue properties regardless of recovery index used. Changes in nodal function curves arising from the use of different recovery indexes mainly depend on pretest effects. This study provides a new approach to a unified interpretation of nodal recovery and fatigue properties.

Delineation of AV conduction pathways by selective surgical transection: effects on antegrade and retrograde transmission.

INTRODUCTION: The role for transitional cells as determinants of AH and HA conduction was examined in the superfused rabbit AV junction. METHODS: Bipolar electrodes and microelectrodes were used to record antegrade A-H and retrograde H-A activation, before and after transection of the transitional cell input to the compact AV node. RESULTS: During pacing from the high right atrium, inferior to the coronary sinus os, beneath the fossa ovalis, or on the anterior limbus, AV Wenckebach block (WB) was mediated by identical transitional cells grouped in close apposition to the compact AV node. Paced WB cycle lengths were shorter from the high right atrium (196+/-12 msec) and inferior to the coronary sinus os (195+/-8 msec) versus the fossa ovalis (217+/-9 msec) or anterior limbus (206+/-11 msec). With His bundle pacing, retrograde HA WB (211+/-17 msec) was observed within the N cell region within the compact AV node. After transection of posterior and superior transitional cell input to the compact AV node, the antegrade AH WB cycle length was prolonged (245+/-18 msec), with an increased WB incidence within the NH region (compact AV node)(5% to 41%; p=0.014). The incidence of retrograde HA WB determined within the NH region was increased (30% to 88%), with a decrease in the stimulus-fast pathway conduction time (98+/-7 to 49+/-6 msec; p<0.01). CONCLUSIONS: The data demonstrate (1) a common transitional cell population determining AH WB, independent of atrial stimulation site, and (2) a plasticity of transitional cell-compact AV node connections, with rapid AH and HA conduction favored by removal of posterior/superior AV nodal input.

The antipsychotic and antiemetic drug prochlorperazine delays the ventricular repolarization of the in situ canine heart.

Electropharmacological effect of the antipsychotic and antiemetic drug prochlorperazine was assessed using the halothane-anesthetized in vivo canine model (n = 5). Up to 10 times higher than the clinically relevant doses of prochlorperazine (< or = 3 mg/kg, i.v.) did not induce cardiohemodynamic collapse in the model. Meanwhile, clinically relevant to supratherapeutic doses (0.3 - 3 mg/kg, i.v.) prolonged the ventricular repolarization period in a dose-related and reverse-use dependent manner that could become proarrhythmic substrates. Thus, caution has to be paid on the use of prochlorperazine particularly for patients with risks of the elevated plasma drug concentration, compromised cardiac repolarization, and/or frequent ventricular premature beats.

Effects of acute systemic endothelin receptor blockade on cardiac electrophysiology in vivo.

BQ-123, a selective endothelin-A receptor antagonist, has been demonstrated to suppress arrhythmias. However, the role of physiologic levels of endogenous endothelin-1 (ET-1) with respect to electrophysiologic properties of the heart is unknown. BQ-123 (0.45, 0.9, 1.8, 3.6, 7.2, and 14.4 microg/kg/min; n = 10) or saline (control, n = 5) was administered IV for 15 minutes of continuous-rate infusion at incremental doses to anesthetized normal pigs. BQ-123 had no effect on PR and QT interval, QRS duration, intraatrial and AV nodal conduction time as well as the atrial, AV nodal, and ventricular effective refractory periods. As compared with baseline, BQ-123 at 7.2 and 14.4 microg/kg/min caused an increase in heart rate (99 +/- 17 versus 110 +/- 14 and 118 +/- 14 bpm, respectively; P < 0.05), shortened sinus node recovery time (818 +/- 165 versus 641 +/- 69 and 609 +/- 74 milliseconds, respectively; P < 0.05) and decreased mean arterial pressure at 14.4 microg/kg/min (95 +/- 18 versus 80 +/- 11 mm Hg; P < 0.05). We conclude that in the normal pig, physiologic levels of ET-1 have no effect on conduction properties of atrial, AV nodal, or Purkinje fibers. However, antagonism of ET-1 by BQ-123 unmasks the effect of ET-1 on maintenance of vasomotor tone, which in turn may affect heart rate and sinus node automaticity in the intact pig.

Fast pathway-His bundle connections in the rabbit heart.

OBJECTIVES: The incidence and the physiologic roles for direct fast pathway-His bundle connections were examined in 102 rabbit hearts. METHODS: Extracellular bipolar and intracellular microelectrode recordings were made from the superfused rabbit AV junction. RESULTS: In 13 of 27 preparations demonstrating anterior extensions of the fast pathway, the retrograde HA ERP and 2:1 block cycle length were shortened (128 +/- 12 and 145 +/- 5 msec, respectively) versus the remaining 89 preparations (178 +/- 15 and 185 +/- 10 msec, respectively, p < 0.01). The former values were similar to the ERP and 2:1 block cycle length of fast pathway transitional cells (128 +/- 23 and 141 +/- 4 msec, respectively), suggestive of a direct fast pathway-His bundle connection. A deflection recorded between the A and H potentials of the His bundle electrogram could be dissociated from both atrial and His bundle activation. Intracellular microelectrode recordings and light microscopy confirmed the deflection to be an accessory pathway consisting of an anterior extension of fast pathway transitional cells connecting the atrium and His bundle. Transection along the AV groove anterior to the compact AV node ( N = 5) increased the retrograde ERP and Wenckebach block cycle length by severing the AH connection, or transection of the penetrating bundle ( N = 4) produced antegrade AH block without altering rapid retrograde conduction. CONCLUSIONS: Fast pathway-His bundle connections were present in 13 of 102 rabbit hearts, providing an anatomic and physiologic basis for rapid retrograde VA conduction and a possible retrograde pathway for sustained AV nodal reentrant tachycardia.

Variability of AV nodal potentials recorded, in vivo: direct demonstration of dual AV nodal physiology.

OBJECTIVES OF STUDY: We developed a method to record extracellular A-V nodal potentials in the beating dog heart, in vivo. METHODS: In eleven Na-pentobarbital anesthetized, open-chest dogs, an octapolar electrode catheter (2 mm rings, 2 mm spacing) was inserted through a purse-string suture in the coronary sinus (CS) distal to the ostium and positioned electrographically so that the tip electrode recorded a His bundle (Hb) potential. RESULTS: Stable recordings of A-V nodal potentials (amplitude, 178 +/- 94 microV; duration 78 +/- 26 msec) were consistently made during sinus rhythm from the second and/or third bipolar pairs of electrodes. Programmed atrial stimulation and vagal stimulation resulted in loss of amplitude and increased duration of the A-V nodal potentials associated with A-H prolongation. In another series of experiments, crushing the sinus node in 6 dogs resulted in AV nodal rhythms with AV nodal potentials of varying amplitudes (132 to 840 microV) and durations (range 25 to 71 msec) as the earliest activation which preceded the Hb, atrial and ventricular deflections. One dog, showing dual AV nodal physiology as documented from the AV nodal function curve, had two distinctly different AV nodal potentials. The low-level, longer duration potentials were associated with longer (slow pathway) A-H intervals; whereas the shorter higher amplitude potentials (fast pathway) showed shorter A-H intervals, each occurring at a critical paced cycle length. CONCLUSION: We conclude that consistent extracellular AV nodal electrograms can be recorded in vivo although the configuration of these potentials varies depending on heart rate, autonomic stimulation and different arrhythmic conditions such as AV nodal escape rhythms and dual AV nodal physiology.

Reentrant circuits in the canine atrioventricular node during atrial and ventricular echoes: electrophysiological and histological correlation.

BACKGROUND: The anatomic-electrophysiological correlation of AV nodal reentry is unclear. To localize reentrant circuits during atrial and ventricular echoes and to characterize sites of slow conduction and block, we correlated histology with electrophysiology of the AV node. METHODS AND RESULTS: In 10 isolated dog hearts, extracellular electrical activity was recorded in Koch's triangle at 208 or 247 sites (interelectrode distance, 0.5 and 0.3 mm) after removal of 0.7 to 1.5 mm of overlying atrial tissue. Resection did not affect refractory periods. Five hearts were subjected to histology. Complete atrial echoes were induced in 1 heart, incomplete atrial echoes in 5 hearts. Unidirectional conduction block occurred at the atrial-transitional cell junction in the superior area. Zones of slow conduction arose at the atrial-transitional or the transitional-compact node junction in the inferior area. Complete reentrant circuits of ventricular echoes were obtained in 5 hearts. Unidirectional conduction block occurred at the compact node-transitional cell junction in the superior area. Localized zones of slow conduction arose at the junctions between the different types of tissue in the inferior area. CONCLUSIONS: In the dog heart, tissue architecture and functional dissociation between the inferior and the superior region of the AV node enable dual physiology and reentry. Slow conduction and functional conduction block occur at the junctions between the different types of tissue in the AV nodal area. Atrial echoes were enabled by conduction block at the atrial-transitional cell junction, whereas during ventricular echoes conduction block occurred at the compact node-transitional cell junction.

The elusive extracellular AV nodal potential: studies from the canine heart, ex vivo.

Various forms of extracellular recordings from the AV node (AVN) have been reported. However, lack of consistent validation have precluded the use of such recordings in experimental and clinical studies. In 14 Langendorff perfused dog hearts, the triangle of Koch (TOK) was exposed and an octapolar electrode catheter (2 mm rings, 2 mm spacing) was inserted under the endocardium so that the bipolar pairs recorded electrograms from the apex to the base of the TOK. All recording were filtered between 0.05 and 250 Hz, except for a His bundle (Hb) recording (30-250 Hz) made from another bipolar electrode catheter placed in the aortic root. Transmembrane action potentials (AP) were recorded close to the sites of extracellular electrograms. Pin electrodes at the periphery of the bath were arranged to register two ECG leads from the volume conductor. During recovery of electrical activity 11 of 14 preparations developed a junctional rhythm that initially manifested only an AV nodal extracellular and corresponding intracellular AV nodal potentials followed gradually by conduction to the Hb and ventricles but no retrograde atrial activation; 3 preparations initially produced Hb rhythms based on extracellular and transmembrane AP recordings from the AVN and Hb. The amplitude and duration of the AVN extracellular potentials (average: 97 +/- 26 microV and 92 +/- 25 msec, respectively) during AVN rhythms, significantly differed from those during atrial pacing (262 +/- 185 microV and 78 +/- 26 msec, p < 0.05). Histologic sections of the sites underlying the electrodes recording AVN potentials showed AVN tissue throughout. We conclude that extracellular AV nodal potentials are independent waveforms with specific qualitative and quantitative characteristics that distinguish them from adjacent atrial, transitional, Hb or ventricular potentials.

Atrial activation sequence during junctional tachycardia induced by thermal stimulation of Koch's triangle in canine blood-perfused atrioventricular node preparation.

Junctional tachycardia is observed during radiofrequency ablation of the slow pathway. The authors investigated the atrial activation sequence during junctional tachycardia induced with thermal stimulation in canine blood-perfused atrioventricular node (AVN) preparation. The canine heart was isolated (n = 7) and cross-circulated with heparinized arterial blood of the support dog. The activation sequence in the region of Koch's triangle (15 x 21 mm) was determined byrecording 48 unipolar electrograms. Atrial sites anterior to the coronary sinus ostium (site AN), close to the His-potential recording site (site N) and superior to site N (site F), were subjected to a continuous temperature rise from 38 degrees C to 50 degrees C with a heating probe. The temperature of the tissue adjacent to the heating site was monitored simultaneously. Junctional tachycardia at a rate of 92+/-12 beats/min with the His potential preceding the atrial one in the His-bundle electrogram was induced during thermal stimulation at site AN (temperature 42.1 degrees C+/-0.9 degrees C) in all seven preparations, whereas junctional tachycardia was induced during stimulation at site N in one and at site F in none. In each case, the temperature rose only at the site of stimulation. The earliest activation site during junctional tachycardia induced by site AN stimulation was at the His-potential recording site in five preparations and the middle of Koch's triangle in the other two. After creating an obstacle between sites AN and N, atrial tachycardia at a rate of 85+/-11 beats/min was induced during site AN stimulation. The earliest activation site during this tachycardia was site AN. Thus, junctional tachycardia induced by thermal stimulation was suggested to originate from the AN thermal stimulation site. The impulse from the stimulation site appeared to conduct via the posterior input to the compact AVN and junctional tachycardia was generated. When the posterior input was interrupted, atrial tachycardia was generated.

His electrogram alternans reveal dual-wavefront inputs into and longitudinal dissociation within the bundle of His.

BACKGROUND: His electrogram (HE) amplitude and morphology changes were observed in our previous studies during transition from "fast" to "slow" atrioventricular nodal (AVN) conduction. This phenomenon and its significance for the dual-AVN electrophysiology are not well recognized and have not been studied. METHODS AND RESULTS: Experiments were performed on 17 healthy rabbit atrial-AVN preparations during standard programmed electrical pacing. HEs were mapped along the His bundle with roving surface electrodes, along with recording of cellular action potentials (APs). HEs recorded from the superior margin of the His bundle were of greater amplitude during basic beats and decreased substantially, by 42+/-19% (P<0.01), when premature A(1)A(2) shortened to 178+/-20 ms. In contrast, the HEs from the inferior margin increased dramatically, 2.9+/-1.7 times (P<0.01), during short A(1)A(2) and remained high until AVN block occurred. In addition, during long A(1)A(2), the superior HEs consistently preceded the inferior by 1.9+/-0.7 ms. In contrast, at short A(1)A(2), the superior HEs occurred 2.7+/-0.8 ms after the inferior. Cellular AP recordings demonstrated clearly the presence of and the transition between early (fast) and late (slow) excitation wavefronts that accompanied HE alternans. CONCLUSIONS: The morphological-electrophysiological evidence from the AV junction suggests that fast and slow wavefronts reach the His bundle differently, producing functional longitudinal dissociation into 2 domains. The characteristic HE alternans recorded from these domains are a new sensitive tool to determine the presence of distinctly different wavefronts and their participation in the conduction during reentrant or other arrhythmias. These findings provide further understanding of the mechanisms of dual-AVN electrophysiology.

The effects of intrinsic nitric oxide on cardiac neural regulation in cats.

UNLABELLED: In this study, we aimed to elucidate the effects of intrinsic nitric oxide (NO) on cardiac neural regulation. Twenty-two cats were anesthetized with 1.5% isoflurane and allocated to Group I (intact; n = 7), Group D (denervated baroreceptors and vagi; n = 8), or Group B (autonomic blockade with i.v. hexamethonium, propranolol, and atropine; n = 7). Cardiac sympathetic nerve activity (CSNA), mean arterial pressure (MAP), sinus heart rate (HR), and A-H and H-V intervals during pacing (150 bpm) were measured before and after i.v. administration of a NO synthase inhibitor, NG-nitro-L-arginine (L-NNA, 30 mg/kg) and after reversal with an excessive dose of L-arginine (300 mg/kg), before and during intermittent electrical stimulation of the posterior hypothalamus. L-NNA significantly increased MAP in Groups I and B, but not in Group D. L-NNA significantly decreased HR and lengthened A-H in Group I, but not in other groups. L-arginine further decreased HR and lengthened A-H unexpectedly. The reasons for these findings could not be determined in this study. L-NNA did not change CSNA. Hypothalamic stimulation did not potentiate L-NNA-induced changes in CSNA, hemodynamic variables, and atrioventricular conduction. In conclusion, intrinsic NO may modulate atrioventricular conduction and sinus rate through a vagal cholinergic, rather than a nonautonomic mechanism. IMPLICATIONS: Elucidating the roles of intrinsic nitric oxide (NO) on cardiac neural regulation is important. In intact, vagotomized, and baroreceptor-denervated or pharmacologically autonomic blockaded cats, an NO synthesis inhibitor was administered, and atrioventricular conduction and cardiac sympathetic neural discharge were measured. The results suggest a vagal cholinergic mechanism of intrinsic NO.