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BACKGROUND: Radiofrequency (RF) energy parameters and chronic lesion characteristics associated with the microbubbles formation have not been yet fully elucidated. OBJECTIVES: The objective of this study was to compare the energy profiles and chronic lesion characteristics associated with RF ablation of the pulmonary vein antrum using three different ablation protocols: (1) avoiding microbubbles; (2) continuous microbubble formation; (3) temperature-guided ablation. METHODS: A 4-mm tip ablation catheter was used for creating RF ablation lesions in 15 adult mongrel dogs. All ablation lesions were created at the posterior aspect of the PV antrum in each animal. Avoiding microbubbles (group 1, n = 5 dogs, 23 lesions), continuous microbubble formation (group 2, n = 5 dogs, 22 lesions), and temperature-guided (group 3, n = 5 dogs, 19 lesions, target temperature 60 degrees C/power limit 50 W) ablation lesions were analyzed. RESULTS: Group 1 showed significantly lower power (19 +/- 8.6 W), lower temperature (50 +/- 4.8 degrees C), higher efficiency-of-heating index (2.9 +/- 0.8 degrees C/W), and lower impedance (109 +/- 24.4 Omega) than groups 2 (38 +/- 8.4 W; 63 +/- 10 degrees C; 1.8 +/- 0.8 degrees C/W; 148 +/- 34.4 Omega) and 3 (44 +/- 12 W; 57 +/- 2.4 degrees C; 1.4 +/- 0.5 degrees C/W; 139 +/- 23.1 Omega) (P < 0.001 vs groups 2 and 3). During ablation, no significant events were detected in group 1, but 11 cases of audible pop, 11 cases of catheter tip charring, and 1 case of fatal myocardial perforation were observed in groups 2 and 3. Transmural lesions were more frequently created in group 1. CONCLUSION: RF energy delivery applying 'avoiding microbubbles' protocol seems to be associated with higher degree of safety and efficacy when compared to temperature-guided and continuous microbubble-formation ablation protocols. [ABSTRACT FROM AUTHOR]

Background: Our aim was to assess how atrial fibrillation (AF) induction, chronicity, and RR interval irregularity affect left atrial (LA) function and size in the setting of underlying heart failure (HF), and to determine whether AF effects can be mitigated by vagal nerve stimulation (VNS)., Methods: HF was induced by 4-weeks of rapid ventricular pacing in 24 dogs. Subsequently, AF was induced and maintained by atrial pacing at 600 bpm. Dogs were randomized into control (n = 9) and VNS (n = 15) groups. In the VNS group, atrioventricular node fat pad stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. LA volume and LA strain data were calculated from bi-weekly echocardiograms., Results: RR intervals decreased with HF in both groups (p = 0.001), and decreased further during AF in control group (p = 0.014), with a non-significant increase in the VNS group during AF. LA size increased with HF (p<0.0001), with no additional increase during AF. LA strain decreased with HF (p = 0.025) and further decreased after induction of AF (p = 0.0001). LA strain decreased less (p = 0.001) in the VNS than in the control group. Beat-by-beat analysis showed a curvilinear increase of LA strain with longer preceding RR interval, (r = 0.45, p <0.0001) with LA strain 1.1% higher (p = 0.02) in the VNS-treated animals, independent of preceding RR interval duration. The curvilinear relationship between ratio of preceding and pre-preceding RR intervals, and subsequent LA strain was weaker, (r = 0.28, p = 0.001). However, VNS-treated animals again had higher LA strain (by 2.2%, p = 0.002) independently of the ratio of preceding and pre-preceding RR intervals., Conclusions: In the underlying presence of pacing-induced HF, AF decreased LA strain, with little impact on LA size. LA strain depends on the preceding RR interval duration.

Background: Cervical vagal nerve stimulation (VNS) can improve left ventricular dysfunction in the setting of heart failure (HF). However, little is known about the impact of VNS on left atrial (LA) function. The aim of this study was to compare LA mechanics and histology between control and VNS-treated animals during HF development., Methods and Results: Fifteen mongrel dogs were randomized into control (n=7) and VNS (n=8) groups. All dogs underwent 8 weeks of high-rate ventricular pacing (at 220 beats per minute for the first 4 weeks to develop HF and another 4 weeks at 180 beats per minute to maintain HF). LA contractile function (LA negative peak strain), conduit function (LA positive peak strain), and reservoir function (LA total strain) were measured from speckle tracking in 2 groups. At the end of the terminal study, the LA appendage was obtained. Baseline LA strains were comparable in the control and VNS-treated dogs. At 4 and 8 weeks of ventricular pacing, all LA strains were decreased and LA volumes were increased in the control group compared with the VNS group (P<0.05). Histological evaluation of the left atrium revealed that percent fibrosis was significantly lower in the VNS versus the control group (8±1% versus 13±1%; P<0.001). Finally, transmitral flow showed decreased atrial contribution to left ventricular filling in the control group (P<0.05)., Conclusions: VNS improved LA function and volumes and suppressed LA fibrosis in the canine high-rate ventricular pacing model. VNS is a novel and potentially useful therapy for improving LA function during HF.

Background: Recently, left ventricular (LV) strain distribution pattern has been assessed in several cardiac disease states. Tachycardia-induced cardiomyopathy (TIC) is an animal model of non-ischemic cardiomyopathy well characterized in terms of global LV dysfunction but with poor understanding of regional variability in LV function. We hypothesized that TIC induces specific changes in LV strain distribution pattern., Methods: Twenty five adult mongrel conscious dogs were trained to lie down calmly for echocardiography. In seven selected dogs, we implanted pacing system for TIC induction under general anesthesia. We measured LV geometry and function, strains, and torsion before and after the development of TIC in awake non-sedated state., Results: In 25 healthy dogs, all three types of normal strain significantly increased from base to apex (p <0.05), while a definite and recognizable twist could be measured due to presence of shear strain. In 7 dogs with TIC, marked changes in LV mechanics occurred throughout the cardiac cycle, resulting in decrease of strain (p <0.001), twist (p <0.05), and negative peak twist rate (p <0.05). Interestingly, the relative decrease of strain due to TIC was more pronounced in the apex (p < 0.001), with the radial strain decreasing the most (p < 0.05)., Conclusion: TIC is accompanied by decreased systolic LV strain and twist deformation, as well as loss of early diastolic recoil. In addition, the decrease of strain was more profound in the apex. This "reverse" distribution of LV strain may help us understand LV dysfunction in the presence of nonischemic etiology.

Introduction: Atrial fibrillation (AF) and heart failure (HF) frequently coexist. We have previously demonstrated that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during AF. Due to withdrawal of vagal activity in HF, the therapeutic effects of AVN-VS may be compromised in the combined condition of AF and HF. Accordingly, this study was designed to evaluate the therapeutic effects of AVN-VS to control ventricular rate in AF and HF., Methods and Results: A combined model of AF and HF was created by implanting a dual chamber pacemaker in 24 dogs. A newly designed bipolar electrode was inserted into the ganglionic AVN fat pad and connected to a nerve stimulator for delivering AVN-VS. In all dogs, HF was induced by high rate ventricular pacing at 220 bpm for 4 weeks. AF was then induced and maintained by rapid atrial pacing at 600 bpm after discontinuation of ventricular pacing. These HF + AF dogs were randomized into control (n = 9) and AVN-VS (n = 15) groups. In the latter group, vagal stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. Compared with the control, AVN-VS had a consistent effect on ventricular rate slowing (by >50 bpm, all P < 0.001) during the entire 6-month observation period that was associated with left ventricular functional improvement. Moreover, AVN-VS was well tolerated by the treated animals., Conclusions: AVN-VS achieved consistent rate slowing, which was associated with improved ventricular function in a canine AF and HF model. Thus, AVN-VS may be a novel, effective therapeutic option in the combined condition of AF and HF., (© 2012 Wiley Periodicals, Inc.)

Background: The atrioventricular node (AVN) plays a vital role in determining the ventricular rate during atrial fibrillation (AF). AF results in profound electrophysiological and structural remodeling in the atria as well as the sinus node. However, it is unknown whether AVN undergoes remodeling during AF., Objective: To determine whether AVN undergoes functional remodeling during AF., Methods: AVN conduction properties were studied in vitro in 9 rabbits with AF and 10 normal controls. A previously validated index of AVN dual-pathway electrophysiology, His-electrogram alternans, was used to monitor fast-pathway or slow-pathway (SP) AVN conduction in these experiments. AVN conduction properties were further studied in vivo in 7 dogs with chronic AF and 8 controls., Results: Compared with the control rabbits, the rabbits with AF had a longer AVN conduction time (83 ± 16 ms vs 68 ± 7 ms; P <.01), longer AVN effective refractory period (141 ± 27 ms vs 100 ± 9 ms; P <.01), an earlier transition from fast-pathway to SP conduction (at a longer prematurity, 249 ± 60 ms vs 171 ± 24 ms; P <.01), and a slower ventricular rate during simulated AF (RR interval 249 ± 42 ms vs 202 ± 12 ms; P <.01). Notably, a larger proportion of conducted beats utilized the SP in AF preparations (92% ± 12% vs 63% ± 32%; P <.05). Long-term AF in dogs resulted in a longer atrioventricular conduction time and AVN effective refractory period and a slower ventricular rate during AF compared with the controls., Conclusions: Pronounced AVN functional electrophysiological remodeling occurs after long-term AF, which could lead to a spontaneous slowing of the ventricular rate. Furthermore, the SP dominance during AF underscores the effectiveness of its modification by ablation for ventricular rate control during AF., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: The precise mechanism(s) governing the phenomenon of AV nodal Wenckebach periodicity is not fully elucidated. Currently 2 hypotheses, the decremental conduction and the Rosenbluethian step-delay, are most frequently used. We have provided new evidence that, in addition, dual pathway (DPW) electrophysiology is directly involved in the manifestation of AV nodal Wenckebach phenomenon., Methods and Results: AV nodal cellular action potentials (APs) were recorded from 6 rabbit AV node preparations during standard A1A2 and incremental pacing protocols. His electrogram alternans, a validated index of DPW electrophysiology, was used to monitor fast (FP) and slow (SP) pathway conduction. The data were collected in intact AV nodes, as well as after SP ablation. In all studied hearts the Wenckebach cycle started with FP propagation, followed by transition to SP until its ultimate block. During this process complex cellular APs were observed, with decremental foot formations reflecting the fading FP and second depolarizations produced by the SP. In addition, the AV node cells exhibited a progressive loss in maximal diastolic membrane potential (MDP) due to incomplete repolarization. The pause created with the blocked Wenckebach beat was associated with restoration of MDP and reinitiation of the conduction cycle via the FP wavefront., Conclusion: DPW electrophysiology is dynamically involved in the development of AV nodal Wenckebach periodicity. In the intact AV node, the cycle starts with FP that is progressively weakened and then replaced by SP propagation, until block occurs. AV nodal SP modification did not eliminate Wenckebach periodicity but strongly affected its paradigm., (© 2011 Wiley Periodicals, Inc.)

Background: Autonomic denervation may suppress atrial fibrillation (AF) vulnerability. This study was designed to assess the short- to mid-term effects of botulinum toxin, a cholinergic neurotransmission blocker, on AF inducibility., Methods and Results: A total of 23 mongrel dogs were studied. The sinus node and atrioventricular node epicardial fat pads were exposed through a right lateral thoracotomy. Botulinum toxin (Botox, 50 U per fat pad) or 0.9% normal saline (control) was injected into the center of each of the 2 fat pads. The electrophysiological effects were evaluated at 1, 2, and 3 weeks (7 to 8 animals at each time point) with and without cervical vagal stimulation. The vagal stimulation effects on the sinus and atrioventricular nodes were inhibited, and dispersion of atrial effective refractory period was lower at 1 week in the Botox group. Significant suppression of AF inducibility was observed at 1 week but disappeared at 2 and 3 weeks. These changes were not observed in the control group., Conclusions: Temporary suppression of vagally mediated AF, for at least 1 week, was achieved with botulinum toxin injection in this canine model. This effect might be associated with reduced dispersion of effective refractory period. A temporary autonomic block using botulinum toxin might be a novel therapeutic option for several clinical conditions such as post-cardiac surgery AF.

Dual atrioventricular (AV) nodal pathway physiology is described as two different wave fronts that propagate from the atria to the His bundle: one with a longer effective refractory period [fast pathway (FP)] and a second with a shorter effective refractory period [slow pathway (SP)]. By using His electrogram alternance, we have developed a mathematical model of AV conduction that incorporates dual AV nodal pathway physiology. Experiments were performed on five rabbit atrial-AV nodal preparations to develop and test the presented model. His electrogram alternances from the inferior margin of the His bundle were used to identify fast and slow wave front propagations. The ability to predict AV conduction time and the interaction between FP and SP wave fronts have been analyzed during regular and irregular atrial rhythms (e.g., atrial fibrillation). In addition, the role of dual AV nodal pathway wave fronts in the generation of Wenckebach periodicities has been illustrated. Finally, AV node ablative modifications have been evaluated. The model accurately reproduced interactions between FP and SP during regular and irregular atrial pacing protocols. In all experiments, specificity and sensitivity higher than 85% were obtained in the prediction of the pathway responsible for conduction. It has been shown that, during atrial fibrillation, the SP ablation significantly increased the mean HH interval (204 ± 39 vs. 274 ± 50 ms, P < 0.05), whereas FP ablation did not produce significant slowing of ventricular rate. The presented mathematical model can help in understanding some of the intriguing AV node mechanisms and should be considered as a step forward in the studies of AV nodal conduction.

Enhancing vagal tone by delivering electrical stimulation to the vagal nerves (VNS) is emerging as a promising novel therapy in heart failure. In addition, VNS is already an FDA-approved therapy for refractory epilepsy and depression. Besides its well-known negative chronotropic, inotropic, and dromotropic effects, VNS has profound effects on cardiac electrophysiology and arrhythmogenesis. This review summarizes current knowledge about the complex relationship between VNS and cardiac arrhythmias. Specifically, the focus is on VNS capability to become a therapeutic strategy along with important electrophysiological alterations that may constitute a potential arrhythmogenic substrate and become a clinical concern.

Role of dual AV nodal pathway physiology in the atrioventricular nodal (AVN) conduction during atrial arrhythmias remains unclear. By using His electrogram alternans (HEA), we have developed a functional model of the atrioventricular conduction that incorporates the dual AV nodal pathway physiology. Experiments performed on 5 rabbit atrial-AVN preparations were used to develop and test the presented AV nodal functional model. HEAs from the inferior margin of the His bundle were used to identify fast and slow wavefront propagations (FP and SP). Conduction curves were calculated by using the model and compared with the real experiments, the root mean square error of the FP and SP were 7 ± 4ms and 3 ± 3 ms respectively. In addition, the model has been used for illustrating the effects of the atrioventricular node modification, which has emerged as one of the alternatives for ventricular rate control during atrial fibrillation. The presented model can help in understanding some of the unclear AV node conduction mechanisms and should be considered as a step forward in understanding the AV node and specifically its dual pathway physiology.

Background: Autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, contributes to the progression of heart failure (HF). Although the therapeutic benefits of sympathetic inhibition with beta-blockers in HF are clear, the role of increased vagal tone in this setting has been less studied. We have investigated the impact of enhancing vagal tone (achieved through chronic cervical vagus nerve stimulation, [VNS]) on HF development in a canine high-rate ventricular pacing model., Methods and Results: Fifteen dogs were randomized into control (n=7) and VNS (n=8) groups. All dogs underwent 8 weeks of high-rate ventricular pacing (at 220 bpm for the first 4 weeks to develop HF and another 4 weeks at 180 bpm to maintain HF). Concomitant VNS, at an intensity reducing sinus rate approximately 20 bpm, was delivered together with the ventricular pacing in the VNS group. At 4 and 8 weeks of ventricular pacing, both left ventricular end-diastolic and -systolic volumes were lower and left ventricular ejection fraction was higher in the VNS group than in the control group. Heart rate variability and baroreflex sensitivity improved in the VNS dogs. Rises in plasma norepinephrine, angiotensin II, and C-reactive protein levels, ordinarily expected in this model, were markedly attenuated with VNS treatment., Conclusions: Chronic VNS improves cardiac autonomic control and significantly attenuates HF development in the canine high-rate ventricular pacing model. The therapeutic benefit of VNS is associated with pronounced anti-inflammatory effects. VNS is a novel and potentially useful therapy for treating HF.

Background: Many patients require temporary inotropic support after cardiac surgery, and dobutamine is one of the commonly used drugs for this purpose. However, dobutamine infusion is frequently associated with unwanted sinus tachycardia. Selective sinus node electrical vagal stimulation through a discrete epicardial ganglionic plexus (fat pad) approach can achieve sinus rate slowing. Because sinus node fat pad vagal stimulation (SNFP-VS) can easily be applied during or after cardiac surgery, we hypothesized that combining selective SNFP-VS with dobutamine could produce desired hemodynamic improvement while avoiding sinus tachycardia in patients when inotropic drug support is needed., Methods: This exploratory experimental study was performed in 7 open-chest dogs. Dobutamine (2.5 to 10 microg x kg(-1) x min(-1)) was infused at a rate producing at least 30% increase in sinus rate and cardiac output. Then electrical SNFP-VS was applied in the epicardial ganglionic plexus located at the right pulmonary vein-atrial junction, to slow the sinus rate back to control level. Hemodynamic data during control, with steady-state dobutamine infusion, and with dobutamine plus SNFP-VS were collected and compared., Results: Dobutamine significantly increased heart rate, systolic and diastolic blood pressures, peak left ventricular systolic pressure, positive and negative maximal derivatives of left ventricular pressure, and cardiac output. Combining SNFP-VS with dobutamine eliminated sinus rate increase while preserving all major hemodynamic benefits. Selective SNFP-VS itself had no direct effect on cardiac contractility during atrial pacing., Conclusions: Combining SNFP-VS with dobutamine could achieve hemodynamic improvement while avoiding sinus tachycardia in this dog model, suggesting that similar strategy may also be applied in patients.

Background: Strong vagus nerve stimulation (VNS) is routinely used to induce and maintain atrial fibrillation (AF) in acute animal studies. Taken as a surrogate of increased vagal tone, such observations suggest an arrhythmogenic role of VNS in AF. In contrast, VNS has been demonstrated to have profound therapeutic effects in heart failure and other ailments., Objective: The purpose of this study was to examine the relationship between right cervical VNS and AF, especially the potential arrhythmogenic effects of therapeutic VNS., Methods: The relationship between VNS intensities and AF inducibility was studied in eight acute dogs at baseline and four different levels of VNS, which were set to prolong spontaneous sinus cycle length (SCL) by 20%, 40%, 60%, or 100%. The effect of mild VNS treatment on AF induction was further investigated in six chronically instrumented conscious dogs. These dogs were implanted with right cervical VNS stimulators and specialized atrial pacemakers. VNS intensity was titrated to slow the sinus rate by 10%., Results: In acute studies, it was found that mild to moderate VNS (i.e., producing < or =40% SCL prolongation) did not increase AF inducibility, while strong VNS (i.e., producing > or =60% SCL prolongation) did. In chronic studies, compared with controls, AF induction did not change during the 4-week VNS treatment., Conclusions: AF inducibility by right cervical VNS is intensity dependent: strong VNS (producing > or =60% SCL prolongation) facilitates AF, while moderate VNS (producing < or =40% SCL prolongation) appears not to affect AF. The nonarrhythmogenic effect of therapeutic chronic VNS was further verified in conscious animals. We conclude that VNS with moderate intensities can be used to deliver therapeutic benefits without arrhythmogenic risk.

Objectives: The aims of this study were to demonstrate the safety and the feasibility of the robotic catheter remote control system (CCS) in endocardial navigation in all cardiac chambers, as well as facilitation of the transseptal puncture., Background: CCS has been developed to facilitate control and precise positioning of catheters within the cardiovascular system., Methods: CCS consists of a remote catheter manipulator, a set up joint, a physician workstation, and a steerable guide catheter (SGC) and sheath. A conventional 4-mm tip catheter was inserted through the SGC to perform mapping of five predefined targets in each cardiac chamber. Seven mongrel dogs were used in this study. Intracardiac echocardiography and three-dimensional (3-D) electroanatomical mapping were integrated with CCS to facilitate catheter manipulation and to guide transseptal puncture. The time to complete the transseptal puncture and the time to complete access to the predefined targets in each cardiac chamber were measured. Gross and microscopic examinations of the accessed and ablation sites were performed to evaluate safety., Results: Transseptal puncture was performed successfully in all animals with a mean time of 7 +/- 3 minutes. Procedure times to access the five targets in the right atrium, right ventricle, left atrium, and left ventricle were 5.6 +/- 1.7, 4.6 +/- 1.5, 13.5 +/- 11.0, 7.0 +/- 2.9 minutes, respectively. There were no intracardiac damages associated with catheter manipulation noted in the excised hearts., Conclusions: Endocardial catheter navigation and mapping using the robotic catheter remote control is safe and feasible. Moreover, the CCS could be used to perform transseptal puncture and left atrial instrumentation.

Background: Major epicardial fat pads contain cardiac ganglionated plexi of the autonomic, predominantly vagal nerves. Vagal denervation may improve the success rate of atrial fibrillation (AF) treatment., Objectives: The purpose of this study was to elucidate the long-term effects of fat pad ablation on the electrophysiologic characteristics of the atrium and AF inducibility., Methods: Six mongrel dogs were studied. Cervical vagal stimulation was applied to determine effects on the sinus node, AV node, atrial effective refractory period (AERP), and AF inducibility. AERP and AF inducibility were evaluated at both the right atrial and left atrial appendages and at the right atrial and left atrial free walls. Radiofrequency energy was delivered epicardially to the entire areas of two major fat pads: right pulmonary vein fat pad and inferior vena cava-left atrium fat pad. Cervical vagal stimulation then was applied to confirm the acute effects of fat pad ablation. The same evaluation was repeated 4 weeks later., Results: The effects of vagal stimulation on the sinus node, AV node, and AERP were significantly eliminated immediately after fat pad ablation. However, these denervation effects disappeared after 4 weeks. At baseline, AF inducibility was increased by vagal stimulation (right atrial appendage: 72% +/- 31% vs 4.8% +/- 12%; right atrial free wall: 75% +/- 31% vs 0.0% +/- 0.0%; left atrial appendage: 60% +/- 29% vs 0.0% +/- 0.0%; left atrial free wall: 65% +/- 42% vs 0.0% +/- 0.0%). Fat pad ablation significantly reduced this vagal stimulation effect (8.3% +/- 20%, 10% +/- 22%, 17% +/- 29%, and 25% +/- 29%, respectively). However, similar to baseline, AF inducibility was strongly augmented by vagal stimulation 4 weeks after fat pad ablation (96% +/- 10%, 100% +/- 0.0%, 100% +/- 0.0%, and 95% +/- 11%, respectively)., Conclusion: Radiofrequency fat pad ablation may not achieve long-term suppression of AF induction in this canine model.

While the heart size maintains a constant proportion to body size, heart function parameters, such as heart rate and cardiac output, show a more complex scaling pattern. How these phenomena affect the long-axis left ventricular (LV) function is unknown. We studied 10 mice, 15 rats, 6 rabbits, 8 mongrel dogs and 38 human volunteers. Doppler tissue echocardiography data were postprocessed to reconstruct mitral annulus (MA) peak systolic velocity and displacement. The relationship between MA peak velocity, MA displacement and LV ejection time, and LV end-diastolic volume (and mass) were fit to an allometric (power-law) equation Y=kMbeta. LV mass varied from 0.062 to 255 g, while end-diastolic volume varied from 0.014 to 205 ml. beta values of the relation between LV ejection time and LV end-diastolic volume and mass were 0.247+/-0.017 and 0.267+/-0.018, respectively. beta values of the relationship between MA displacement and LV end-diastolic volume and mass were 0.358+/-0.047 and 0.390+/-0.051 (P<0.023 versus beta of LV ejection time). beta values of the relationship between MA peak systolic velocity and LV end-diastolic volume and mass were 0.096+/-0.012 and 0.100+/-0.013, respectively (P<0.0001 versus 0). Finally, beta values of the relationship between the long-to-short axis displacement ratio and LV end-diastolic volume and mass were 0.077+/-0.017 and 0.086+/-0.019 (P<0.0001 versus 0). We conclude that MA velocity, displacement, and long-to-short axis displacement ratio scale allometrically to heart size. This reduces the relative long-axis contribution to heart function in small mammals.

Background: Mechanistic roles of the immediate increase in left atrial (LA) pressure in pacing-induced congestive heart failure have not been clearly understood. We evaluated the impact of asynchronous rapid ventricular pacing on LA hemodynamics in this model., Methods: Transthoracic and transesophageal echocardiography and hemodynamic assessment were performed in 23 healthy mongrel dogs. Data were acquired before and 5 minutes after initiation of rapid right ventricular pacing (200/min)., Results: At 5 minutes after initiation of the pacing, giant pulmonary venous (PV) flow reversal (-76 cm/s) was observed in association with 1:1 ventriculoatrial conduction or complete atrioventricular dissociation. This giant PV flow reversal corresponded to an inappropriately timed atrial contraction, especially during systole. Cardiac output (3.21 vs 2.00 L/min, P < .001) was decreased corresponding to the decrease in the forward blood volumes as described by decrease in the Doppler left ventricular (LV) outflow (8.99 vs 4.73 cm, P < .0001), mitral inflow (6.89 vs 3.19 cm, P < .0001), and PV flow (14.15 vs 7.22 cm, P < .0001) velocity integrals. As a result, there was a marked elevation of the mean pulmonary capillary wedge (9.1 vs 17.1 mm Hg, P < .001) and LV end-diastolic (8.2 vs 17.4 mm Hg, P < .01) pressures leading to congestive heart failure., Conclusions: The giant PV flow reversal seen during asynchronous rapid right ventricular pacing corresponds to an inappropriate atrial contraction, immediately elevates LA pressure, and may initially promote congestive heart failure. The increase in LV end-diastolic pressure associated with decreased LV ejection fraction caused decrease in the LV filling volume leading to further increase in the LA pressure. This sustained marked elevation in the LA pressure and LV end-diastolic pressure could contribute to the heart failure process.

Background: Although left ventricular (LV) contractility in atrial fibrillation (Af) is known to change in a beat-to-beat fashion, little is known about the changes in LV compliance in Af., Material/methods: We experimentally induced tachycardic Af (average heart rate - 154 beats per minute) in 18 sheep. LV volume and pressure were simultaneously monitored using a conductance catheter. LV end-diastolic volume (V(ED)) and pressure (P(ED)) were plotted in a beat-to-beat fashion and fitted to the following exponential equation (P(ED)=gamma x e(b x V(ED))) in each animal. A random effects model was constructed to determine if the intercepts and slopes differ., Results: In all animals, those plots after the induction of Af fit quite well to the exponential function (r=0.834+/-0.184) by gating short preceding interval (RR1) beats. By simply taking the natural logarithm of both sides in the equation, the linear relationship (ln(P(ED)) =alpha+ betaxV(ED), where a = lng) was observed in all animals before (normal sinus rhythm, NSR) and after the induction of Af. Only two of 18 intercepts and four of 18 slopes deviate between NSR and Af. Most interestingly, the random effects model clearly detailed that the average animal had intercepts and slopes that were not discernibly different between NSR and Af., Conclusions: Unlike LV contractility, myocardial compliance did not change after the acute induction of Af. These interesting results may give us insights into the understanding of the physiology in acute rapid Af.

Objectives: The aim of this study was to achieve regular slow ventricular rhythm during atrial fibrillation (AF) without destroying the AV node (AVN)., Background: Recent experimental and clinical studies have demonstrated that selective AVN vagal stimulation (AVN-VS) can be used to slow ventricular rate during AF; however, an irregular rhythm remains. Alternatively, ventricular on-demand (VVI) pacing achieves rate regularization but at rates faster than the already fast intrinsic rate during AF. We hypothesized that AVN-VS combined with VVI pacing would achieve slow, regular rhythm during AF without requiring AVN ablation., Methods: AF was induced in eight dogs. AVN-VS was applied to the epicardial fat pad that projects vagal nerve fibers to the AVN. A computer-controlled algorithm adjusted AVN-VS intensity to achieve three levels of mean ventricular RR interval: 75%, 100%, or 125% of the spontaneous sinus cycle length. At each of the three levels, concomitant VVI pacing was delivered at a constant cycle length equal to the corresponding target. Hemodynamic measurements were performed during the study to elucidate the advantages of the proposed method., Results: AF resulted in rapid, irregular ventricular rates (RR = 287 +/- 36 ms, or 56% of sinus cycle length). AVN-VS achieved average ventricular rate slowing to the three target levels in all dogs (RR increased to 381 +/- 41, 508 +/- 54, and 632 +/- 68 ms, respectively). At each of the three target rate levels, AVN-VS combined with VVI pacing fully eliminated rate irregularities. The regular slow ventricular rhythms during AF were associated with significant hemodynamic improvement., Conclusions: A novel approach combining AVN-VS with VVI pacing results in a regular, slow ventricular rhythm during AF that does not necessitate AVN ablation. Rate regularization achieved by this approach was associated with pronounced hemodynamic benefits during AF.

Objectives: The aim of this study was to assess whether Frank-Starling mechanism has an independent effect on left ventricular (LV) performance in atrial fibrillation (AF)., Background: Ventricular performance in AF depends on variable contractility through the interval-force mechanism based on the ratio of preceding and pre-preceding RR intervals (RR(p)/RR(pp)). The impact of end-diastolic volume (EDV) variability, through the Frank-Starling mechanism, is not well understood., Methods: We induced AF in 16 open chest dogs. RR intervals, LV pressure, LV volume, and aortic flow were collected for >400 beats during rapid AF (ventricular cycle length 292 +/- 66 ms). In six of the dogs, additional data were collected while average ventricular cycle length was prolonged from 258 +/- 34 ms to 445 +/- 80 ms by selective vagal nerve stimulation of the AV node., Results: The relations of maximal LV power (LVPower) and peak LV pressure derivative (dP/dt) versus RR(p)/RR(pp) were fitted to the equation y = A * (1 - EXP (RR(p)/RR(pp)min - RR(p)/RR(pp))/C) and the residuals (RES) of these relations were analyzed. LVPower and dP/dt strongly correlated with RR(p)/RR(pp) (r(2) = 0.67 +/- 0.12 and 0.66 +/- 0.12, P < .0001 for all correlations). Importantly, RES-LVPower and RES-dP/dt showed linear correlation with EDV (r(2) = 0.20 +/- 0.14 and r(2) = 0.24 +/- 0.17, P < .01 for all correlations). In the six dogs with slowed average ventricular rate, the slope of both residual relationships (RES-LVPower vs EDV and RES- dP/dt vs EDV) decreased (P < .03 for both)., Conclusions: The Frank-Starling mechanism contributes to ventricular performance in AF independently of the interval-force effects of the beat-to-beat variability in cardiac contractility. The Frank-Starling mechanism is sensitive to the average ventricular rate.

Patients with paroxysmal atrial fibrillation (AF) who have recently converted from AF to sinus rhythm often exhibit a restrictive Doppler pattern in the transmitral flow (TMF) velocity. However, the mechanism of this phenomenon has not been well defined. We evaluated the temporal change of TMF pattern and hemodynamics after conversion of AF to in sinus rhythm in an animal model. Eight open-chest dogs underwent 3 hours of pacing-induced AF. TMF velocities and pressure data were acquired at baseline (sinus rhythm), immediately after conversion of AF, and every 10 minutes thereafter. Early diastolic TMF velocity was increased immediately after conversion and recovered to the baseline value in 20 minutes. Atrial systolic TMF velocity was reduced after AF and recovered to baseline value in 20 to 30 minutes. Early diastolic/atrial systolic TMF velocity was increased after conversion, and recovered to baseline value in 20 to 30 minutes. The mean left atrial (LA) pressure increased immediately, 10 and 20 minutes after the conversion of AF to sinus rhythm. The left ventricular end-diastolic pressure was increased and positive left ventricular dP/dt and tau were decreased immediately after AF, whereas they recovered within 10 minutes. In conclusion, a pseudorestrictive pattern of TMF after AF occurred as a result of transient LA mechanical functional impairment and increased LA pressure caused by LA stunning. Transient left ventricular diastolic dysfunction also effected the TMF velocity immediately after the conversion from AF to sinus rhythm, although it recovered faster than LA mechanical dysfunction.

Atrial fibrillation (AF) is the most common arrhythmia. Currently there are two broad strategic treatment options for AF: rhythm control and rate control. For rhythm control, the treatment is directed toward restoring and maintaining the sinus rhythm. For rate control, the intention is to slow ventricular rate while allowing AF to continue. In both cases anticoagulation therapy is recommended. The results of currently available clinical trials demonstrated clearly that rate control is not inferior to rhythm control. Thus, rate control is an acceptable primary therapy for many AF patients. The rate control can be achieved essentially by depressing or modifying the filtering properties of the atrioventricular (AV) node. This can be attained by medications that depress the impulse transmission within the AV node, by anatomic modification of the AV communications, as well as by autonomic manipulations that produce AV node negative dromotropic effect. We are reviewing current clinical and newer experimental modalities aimed at enhancing the lifesaving function of this remarkable nodal structure.

Left ventricular (LV) diastolic function during atrial fibrillation (AF) remains poorly understood due to the complex interaction of factors and beat-to-beat variability. The purpose of the present study was to elucidate the physiological determinants of beat-to-beat changes in LV diastolic function during AF. The RR intervals preceding a given cardiac beat were measured from the right ventricular electrogram in 12 healthy open-chest mongrel dogs during AF. Doppler echocardiography and LV pressure and volume beat-to-beat analyses were performed. The LV filling time (FT) and early diastolic mitral inflow velocity-time integral (E(vti)) were measured using the pulsed Doppler method. The LV end-diastolic volume (EDV), peak systolic LV pressure (LVP), minimum value of the first derivative of LV pressure curve (dP/dt(min)), and the time constant of LV pressure decay (tau) were evaluated with the use of a conductance catheter for 100 consecutive cardiac cycles. Beat-to-beat analysis revealed a cascade of important causal relations. LV-FT showed a significant positive linear relationship with E(vti) (r = 0.87). Importantly, there was a significant positive linear relationship between the RR interval and LV-EDV in the same cardiac beat (r = 0.53). Consequently, there was a positive linear relationship between LV-EDV and subsequent peak systolic LVP (r = 0.82). Furthermore, there were significant positive linear and negative curvilinear relationships between peak systolic LVP and dP/dt(min) (r = 0.95) and tau (r = -0.85), respectively, in the same cardiac beat. In addition, there was a significant negative curvilinear relationship between dP/dt(min) and tau (r = -0.86). We have concluded that the determinants of LV diastolic function in individual beats during AF depend strongly on the peak systolic LVP. This suggests that the major benefit of slower ventricular rate appears related to lengthening of LV filling interval, promoting subsequent higher peak systolic LVP and greater LV relaxation.

Objectives: Atrioventricular node (AVN) modification is one of the alternatives for ventricular rate control in patients with drug refractory atrial fibrillation (AF). However, the underlying mechanisms, and in particular the role of the dual pathway electrophysiology is not clear. By using a novel index, His electrogram (HE) alternans, we have previously demonstrated in rabbits that both the slow (SP) and the fast pathways (FP) are involved in AVN conduction during AF. This electrophysiological-morphological study was designed to address the role of selective FP ablation on AVN conduction during AF., Methods and Results: In 12 rabbit AVN preparations dual pathway conduction was confirmed by HE alternans during A1A2 pacing protocol, as well as during AF. On average 48% of the conducted beats during AF utilized the FP. Selective FP ablation (n=12) guided by HE alternans resulted in only-SP conduction, with longer AVN conduction time at basic beats, but without change of AVN effective refractory period (ERP). Interestingly, despite elimination of all FP-conducted beats during AF, the selective FP ablation allowed previously concealed SP beats to be conducted, resulting in little net effect on the ventricular rate (average His-His interval 199+/-10 ms before versus 201+/-13 ms after FP ablation, p>0.05). Morphological evidence indicated that FP ablation created lesions within the transitional cells of the superior approaches at the junction between the central fibrous body and the AVN. However, extension of FP ablation lesion into the compact AVN domain resulted in non-selective AVN modification and slowing of ventricular rate during AF., Conclusions: Despite its longer ERP, FP is responsible for a substantial number of ventricular beats during AF. However, selective FP ablation has a minor effect on ventricular rate. The most likely mechanism for this phenomenon is that FP ablation allows previously concealed SP beats to be conducted. On the other hand, ventricular rate slowdown could be achieved if FP ablations caused collateral damage in the compact node. This study highlights the usefulness of HE alternans as a novel tool to monitor dual pathway conduction during AF and to guide AVN modification.

The shape of the shock waveform influences defibrillation efficacy. However, the optimal combination between capacitance size and truncation/tilt which can determine monophasic waveform's shape, has not been determined for external defibrillation. The purpose of this study was to assess the effects of varying capacitance and tilt on external defibrillation using exponential monophasic waveforms. In a pig model of external defibrillation (n = 10, 30 +/- 6 kg), nine exponential monophasic waveforms combining three capacitance values (30 microF, 60 microF, and 120 microF) and three tilt values (55%, 75%, and 95%) were tested randomly. The energy and leading edge voltage at 50% defibrillation success (E50 and V50) were used to evaluate defibrillation efficacy. E50 and V50 were determined by the Bayesian technique. The lowest stored E50 for the 30microF, 60 microF, and 120 microF waveforms were 90 +/- 12 J (95% tilt), 106 +/- 45 J (55% tilt), and 107 +/- 52 J (75% tilt), respectively. The lowest V50 for the 30 microF, 60 microF, and 120 microF waveforms were 2,439 +/- 166 V (95% tilt), 1,849 +/- 375 V (55% tilt), and 1,301 +/- 322 V (75% tilt), respectively. The average current at external defibrillation threshold demonstrated a strength versus pulse duration relationship similar to that seen with pacing. Reducing capacitance has the same effect as truncating the waveform. The E50 is more sensitive to tilt values changes in larger capacitance waveforms. This study suggests that the optimal combination between capacitance and tilt may be 120 microF and 55%-75% for external defibrillation.

Background: Traditional tools to study dual-pathway atrioventricular nodal (AVN) electrophysiology are not applicable in subjects with permanent atrial fibrillation (AF). The presence of fast-pathway (FP) and slow-pathway (SP) wavefronts and their possible modification remain uncertain in this condition. We demonstrated previously that His electrogram (HE) alternans can determine whether the FP or the SP reaches the His bundle on a beat-by-beat basis. We have now applied this novel index to monitor dual-pathway conduction and the effects of SP modification during AF., Methods and Results: In 12 rabbit AVN preparations, HE alternans were confirmed during a standard A(1)A(2) pacing protocol. During AF, in 9 of the 12 hearts, HE alternans indicated the presence of dual pathways. Successful SP modification guided by the HE alternans eliminated the SP, resulting in a predominantly FP conduction during AF in all hearts. This increased the average His-His interval (204+/-14 versus 276+/-51 ms, P<0.001). Morphological studies revealed that SP modification damaged only the posterior extension of the AVN., Conclusions: We have demonstrated for the first time in rabbits that HE alternans permit "visualization" of dual-pathway electrophysiology and confirmed the presence of both FP and SP wavefronts during AF. This novel index has been used in a selective SP ablation that resulted in a significant slowing of the ventricular rate. HE alternans provide a new insight into the mechanisms of AVN conduction and could guide AVN modification for ventricular rate control in AF clinically.

Although we soon will be marking the 100th anniversary of the discovery of the atrioventricular (AV) node, the mysteries of this most complex of all parts of the conduction system of the heart remain. We are still battling controversies related to the precise morphology of the AV node and its atrial approaches. We are still debating the exact reentrant pathways of the AV nodal reentrant tachycardia. We are still uncertain if the so-called dual AV nodal electrophysiology encompasses two or more pathways, and what exactly makes these pathways in the absence of distinct insulated cables between the atrium and the AV node. It may be just surprising, in view of the above limitations, that current level of knowledge has nevertheless made possible some of the most spectacular successes in the modern cardiac electrophysiology. Thus, the cases of typical AVNRT are cured with a very high rate of success by radiofrequency ablations, increasing the quality of life of thousands of patients. AV nodal modifications are being performed to slow the ventricular rate during atrial fibrillation, although more progress is needed in this endeavor. The goal of the present review is to outline the major anatomic and electrophysiologic efforts in understanding the mechanisms underlying the dual pathway AV nodal propagation and to trace some novel approaches that promise to widen the horizon of the experimental and clinical fields.

Although it has been suggested that multisite ventricular pacing alleviates heart failure by restoring ventricular electrical synchronization, the respective roles of voltage output, interventricular delay, and pacing sites in the development of ventricular arrhythmias occurrence have not been studied during biventricular pacing or LV pacing. Voltage-sensitive dye was used in eight ischemic Langerdorff-perfused guinea pig hearts to measure ventricular activation times and examine conduction patterns during multisite pacing from three RV and four LV sites. The hearts were stained with di-4-ANEPPS and mapped with a 16 x 16 photodiode array at a resolution of 625 microns per diode. Isochronal maps of RV and LV activation were plotted. Ischemia was produced by gradually halving the perfusion output over 5 minutes. Pacing the RV apex and the base of the LV anterior wall was associated with the most homogeneous and rapid activation pattern (28 +/- 9 vs 41 +/- 12 ms with the other configurations, P < 0.01), and no inducible arrhythmia. In six hearts, ventricular tachycardia could be induced when pacing from the right and left free walls with 20 ms of interventricular delay, at six times the pacing threshold output. In four hearts, simultaneous RV and LV pacing at high voltage output induced ventricular fibrillation with complex three-dimensional propagation patterns, independently of the pacing sites. During biventricular pacing with ischemia, pacing at high voltage output with a long interventricular delay is likely to induce ventricular arrhythmias, particularly when left and right pacing results in a conduction pattern orthogonal to the ventricular myocardial fibers orientation.

Atrial fibrillation (AF) is characterized by short and irregular ventricular cycle lengths (VCL). While the beneficial effects of heart rate slowing (i.e., the prolongation of VCL) in AF are well recognized, little is known about the impact of irregularity. In 10 anesthetized dogs, R-R intervals, left ventricular (LV) pressure, and aortic flow were collected for >500 beats during fast AF and when the average VCL was prolonged to 75%, 100%, and 125% of the intrinsic sinus cycle length by selective atrioventricular (AV) nodal vagal stimulation. We used the ratio of the preceding and prepreceding R-R intervals (RR(p)/RR(pp)) as an index of cycle length irregularity and assessed its effects on the maximum LV power, the minimum of the first derivative of LV pressure, and the time constant of relaxation by using nonlinear fitting with monoexponential functions. During prolongation of VCL, there was a pronounced decrease in curvature with the formation of a plateau, indicating a lesser dependence on RR(p)/RR(pp). We conclude that prolongation of the VCL during AF reduces the sensitivity of the LV performance parameters to irregularity.

Background: Selective atrioventricular nodal (AVN) vagal stimulation (AVN-VS) has emerged as a novel strategy for ventricular rate (VR) control in atrial fibrillation (AF). Although AVN-VS preserves the physiological ventricular activation sequence, the resulting rate is slow but irregular. In contrast, AVN ablation with pacemaker implantation produces retrograde activation (starting at the apex), with regular ventricular rhythm. We tested the hypothesis that, at comparable levels of VR slowing, AVN-VS provides hemodynamic benefits similar to those of ablation with pacemaker implantation., Methods and Results: AVN-VS was delivered to the epicardial fat pad that projects parasympathetic nerve fibers to the AVN in 12 dogs during AF. A computer-controlled algorithm adjusted AVN-VS beat by beat to achieve a mean ventricular RR interval of 75%, 100%, 125%, or 150% of spontaneous sinus cycle length. The AVN was then ablated, and the right ventricular (RV) apex was paced either irregularly (i-RVP) using the RR intervals collected during AVN-VS or regularly (r-RVP) at the corresponding mean RR. The results indicated that all 3 strategies improved hemodynamics compared with AF. However, AVN-VS resulted in significantly better responses than either r-RVP or i-RVP. i-RVP resulted in worse hemodynamic responses than r-RVP. The differences among these modes became less significant when mean VR was slowed to 150% of sinus cycle length., Conclusions: AVN-VS can produce graded slowing of the VR during AF without destroying the AVN. It was hemodynamically superior to AVN ablation with either r-RVP or i-RVP, indicating that the benefits of preserving the physiological antegrade ventricular activation sequence outweigh the detrimental effect of irregularity.

Background: Left ventricular contractility in atrial fibrillation is known to change in a beat to beat fashion, but there is no gold standard for contractility indices in atrial fibrillation, especially those measured non-invasively., Objective: To determine whether the non-invasive index of contractility "preload-adjusted PWR(max)" (maximal ventricular power divided by the square of end diastolic volume) can accurately measure left ventricular contractility in a beat to beat fashion in atrial fibrillation., Methods: Atrial fibrillation was induced experimentally using 60 Hz stimulation of the atrium and maintained in 12 sheep; four received diltiazem, four digoxin, and four no drugs (control). Aortic flow, left ventricular volume, and left ventricular pressure were monitored simultaneously. Preload-adjusted PWR(max), the slope of the end systolic pressure-volume relation (E(max)), and the maximum rate of change of left ventricular pressure (dP/dt(max)) were calculated in a beat to beat fashion., Results: Preload-adjusted PWR(max) correlated linearly with load independent E(max) (p < 0.0001) and curvilinearly with load dependent dP/dt(max) (p < 0.0001), which suggested the load independence of preload-adjusted PWR(max). After five minutes of diltiazem administration, preload-adjusted PWR(max), dP/dt(max), and E(max) fell significantly (p < 0.0001) to 62%, 64%, and 61% of baseline, respectively. Changes were not significant after five minutes of digoxin (103%, 98%, and 102%) or in controls (97%, 96%, and 95%)., Conclusions: Preload-adjusted PWR(max) correlates linearly with E(max) and is a useful measure of contractility even in atrial fibrillation. Non-invasive application of this method, in combination with echocardiography and tonometry, may yield important information for optimising the treatment of patients with atrial fibrillation.

Although the beneficial effects of ventricular rate (VR) slowing during atrial fibrillation (AF) are axiomatic, the precise relationship between VR and hemodynamics has not been determined. We hypothesized that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) by varying the nerve stimulation intensity could achieve precise graded slowing and permit evaluation of an optimal VR during AF. The aims of the present study were the following: 1) to develop a method for computerized vagally controlled VR slowing during AF, 2) to determine the hemodynamic changes at each level of VR slowing, and 3) to establish the optimal anterograde VR during AF. AVN-VS was delivered to the epicardial fat pad that projects parasympathetic nerve fibers to the AVN in 14 dogs. Four target average VR levels, corresponding to 75%, 100%, 125%, and 150% of the sinus cycle length (SCL), were achieved by computer feedback algorithm. VR slowing resulted in improved hemodynamics and polynomial fit analysis found an optimum for the cardiac output at VR slowing of 87% SCL. We conclude that this novel method can be used to maintain slow anterograde conduction with best hemodynamics during AF.

Unlabelled: Auxiliary shocks (AS) from electrodes sutured to the left ventricle (LV) prior to primary biphasic shocks (PS) have been shown to reduce defibrillation thresholds (DFT). Two capacitors are required to generate these waveforms. We investigate delivery of AS from one capacitor using a novel waveform. The epicardial surface of the LV is accessed transvenously via the middle cardiac vein (MCV) avoiding a thoracotomy., Methods: A defibrillation electrode was placed in the right ventricle (RV) and superior vena cava (SVC) in 12 pigs (37+/-2 kg). A 50x1.8 mm electrode was inserted in the MCV through a guide catheter. A can was placed in the left pectoral region. A monophasic AS (100 microF, 1.5 J) was delivered along one pathway before switching to deliver a biphasic waveform (40% tilt, 2 ms phase 2) along another. DFTs (PS+AS) were assessed using a binary search. Two configurations not incorporating AS acted as controls. DFTs were compared using repeated measures analysis of variance., Results: DFTs of the four novel configurations (AS/PS) were: RV-->Can/MCV-->Can=14.9+/-3.7 J, MCV-->Can/RV-->Can=17.2+/-5.7 J, RV-->SVC+Can/MCV-->SVC+Can=13.4+/-4.6 J, MCV-->SVC+Can/RV-->SVC+Can=17.1+/-5.9 J. Delivering AS in the RV followed by PS in the MCV reduced the DFT (RV-->Can (19.9+/-7.3 J, P<0.01) and RV-->SVC+Can (19.2+/-6.0 J, P<0.05))., Conclusions: Delivering AS prior to PS in the MCV reduces the DFT by up to a third compared to conventional configurations of RV-->Can and RV-->SVC+Can. This is possible using only a single capacitor and an entirely transvenous approach to the LV.

Although the atrioventricular node (AVN) plays a vital role in blocking many of the atrial impulses from reaching the ventricles during atrial fibrillation (AF), a rapid irregular ventricular rate nevertheless persists. The goals of the present study were to explore the feasibility of novel epicardial selective vagal nerve stimulation for slowing of the ventricular rate during AF and to characterize the hemodynamic benefits in vivo. Electrophysiological-echocardiographic experiments were performed on 11 anesthetized open-chest dogs. Hemodynamic measurements were performed during three distinct periods: 1) sinus rate, 2) AF, and 3) AF with vagal nerve stimulation. AF was associated with significant deterioration of all measured parameters (P < 0.025). The vagal nerve stimulation produced slowing of the ventricular rate, significant reversal of the pressure and contractile indexes (P < 0.025), and a sharp reduction in one-half of the abortive ventricular contractions. The present study provides comprehensive evidence that slowing of the ventricular rate during AF by selective ganglionic stimulation of the vagal nerves that innervate the AVN successfully improved the hemodynamic responses.

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 clinical assessment of left ventricular (LV) systolic function during atrial fibrillation (AF) is unreliable and difficult because of beat-to-beat variability. We evaluated an index for the estimation of LV systolic function in AF that is based on the relationship between the preceding (R-R1) and prepreceding (R-R2) R-R intervals. LV Doppler stroke volume (SV), ejection fraction (EF), peak aortic flow rate (AoF) and the maximum value of the first derivative of the LV pressure curve (dP/dt(max)) were evaluated in 13 healthy open-chest dogs during triggered AF. All parameters showed a significantly strong positive linear relationship with the ratio of R-R1/R-R2 (r = 0.65, 0.74, 0.75, and 0.70 for SV, EF, AoF, and dP/dt(max), respectively). The calculated value of LV systolic parameters at R-R1/R-R2 = 1 in the linear regression line showed a good relationship and an agreement with the measured average value of the parameter over all cardiac cycles (SV, 12.1 vs. 12.8 ml; EF, 49.6 vs. 51.2%; AoF, 1.37 vs. 1.48 l/min; and dP/dt(max), 2,323 vs. 2,454 mmHg/s). Using the LV systolic parameters estimated at R-R1/R-R2 = 1 in the linear regression line allows the LV contractile function to be accurately and reproducibly evaluated during AF and obviates the less-reliable process of averaging multiple cardiac cycles.

The remarkable success of radiofrequency ablation in recent decades in curing atrioventricular nodal reentrant tachycardias has intensified efforts to provide a solid theoretical basis for understanding the mechanisms of atrioventricular transmission. These efforts, which were made by both anatomists and electrophysiologists, frequently resulted in seemingly controversial observations. Quantitatively and qualitatively, our understanding of the mysteries of propagation through the inhomogeneous and extremely complex atrioventricular conduction axis is much deeper than it was at the beginning of the past century. We must go back to the initial sources, nonetheless, in an attempt to provide a common ground for evaluating the morphological and electrophysiological principles of junctional arrhythmias. In this review, we provide an account of the initial descriptions, which still provide an appropriate foundation for interpreting recent electrophysiological findings.

Introduction: The use of two independent, fully discharging capacitors for each phase of a biphasic defibrillation waveform may lead to the design of a simpler, smaller, internal defibrillator. The goal of this study was to determine the optimal combination of capacitor sizes for such a waveform., Methods and Results: Eight full-discharge (95/95% tilt), biphasic waveforms produced by several combinations of phase-1 capacitors (30, 60, and 90 microF) and phase-2 capacitors (1/3, 2/3, and 1.0 times the phase-1 capacitor) were tested and compared to a single-capacitor waveform (120 microF, 65/65% tilt) in a pig ventricular fibrillation model (n = 12, 23+/-2 kg). In the full-discharge waveforms, phase-2 peak voltage was equal to phase-1 peak voltage. Shocks were delivered between a right ventricular lead and a left pectoral can electrode. E50s and V50s were determined using a ten-step Bayesian process. Full-discharge waveforms with phase-2 capacitors of < or =40 microF had the same E50 (6.7+/-1.7 J to 7.3+/-3.9 J) as the single-capacitor truncated waveform (7.3+/-3.7 J), whereas waveforms with phase-2 capacitors of > or =60 microF had an extremely high E50 (14.5+/-10.8 J or greater, P < 0.05). Moreover, of the former set of energy-efficient waveforms, those with phase-1 capacitors of > or =60 microF additionally exhibited V50s that were equivalent to the V50 of the single-capacitor waveform (344+/-65 V to 407+/-50 V vs 339+/-83 V)., Conclusion: Defibrillation efficacy can be maintained in a full-discharge, two-capacitor waveform with the proper choice of capacitors.

Background: Clinical applications of the principles of dual atrioventricular nodal (AVN) electrophysiology in the treatment of AVN reentrant tachycardias rely on empirical findings, such as discontinued conduction curves or the presence of specific catheter-recorded signals. However, neither the shape of the conduction curve nor the surface electrograms have been validated as functionally related to the presence of slow or fast wavefronts., Methods and Results: We performed in vitro studies using 10 rabbit atrial-AVN preparations. A bipolar roving electrode was used to explore the endocardial surface of the triangle of Koch during programmed electrical stimulation. Microelectrodes were impaled in AVN cells to correlate surface and intracellular responses. In 7 preparations, a specific area near the compact cell region produced surface electrograms that were dissociated in 2 distinct components, with progressive shortening of prematurity. Similar dissociation was demonstrated during Wenckebach periodicity and increased vagal tone. Cellular recordings supported the presence of early ("fast") and late ("slow") wavefronts, with different refractory properties. Although the fast-slow transition was a basis for discontinued propagation, the AVN conduction curves were smooth in the majority of cases., Conclusions: Exploration of the triangle of Koch during programmed pacing reveals the presence of dual-wavefront surface potentials. Clinical confirmation of these AVN potentials could provide a new, sensitive tool in defining dual AVN electrophysiology.

Objectives: The role of the atrial inputs for the conduction through the atrioventricular node (AVN) at slow rates and during reentrant tachycardia is well acknowledged, although still controversial. However, the relationship between the sequence and rate of atrial engagement of the AVN inputs and the resulting ventricular rate during high atrial rate remains unclear. This study provides quantitative description of complex AVN input-output correlations determining the ventricular rate during random high atrial rate., Methods and Results: 12 rabbit heart preparations were used to evaluate the ventricular rate during programmed regular high atrial rate pacing or random pacing from eight atrial sites. Electrograms were recorded at the posterior (P) and anterior (A) AVN inputs, and at the bundle of His along with nodal cellular action potentials. Lorenz-plots and input-output-rate correlations were used to quantify the ventricular rate under different pacing protocols. Small alternations in the sequence of activation of P and A resulted in substantial changes of the organization of the intranodal cellular responses and the ventricular rate. The ventricular rate was shown to be significantly dependent on the site of high rate pacing (P < 0.01) and on the resulting mean rate of inputs activation. Furthermore, the asymmetry between P- and A-bombardment was an important determinant, so that high ventricular rate was associated with large difference between the inputs rates and vice versa (P < 0.05)., Conclusions: The prevailing ventricular rate during high atrial rate is a complex dynamic parameter that depends not only on the global mean atrial rate but, in a major part, on the differential bombardment of the AVN inputs and on the site of initiation of the atrial wave fronts.

Background: Phase-2 voltage and maximum pulse width are dependent on phase-1 pulse characteristics in a single-capacitor biphasic waveform. The use of 2 separate output capacitors avoids these limitations and may allow waveforms with lower defibrillation thresholds. A previous report also suggested that the optimal tilt may be >70%. This study was designed to determine an optimal biphasic waveform by use of a combination of 2 separate and fully (95% tilt) discharging capacitors., Methods and Results: We performed 2 external defibrillation studies in a pig ventricular fibrillation model. In group 1, 9 waveforms from a combination of 3 phase-1 capacitor values (30, 60, and 120 microF) and 3 phase-2 capacitor values (0=monophasic, 1/3, and 1.0 times the phase-1 capacitor) were tested. Biphasic waveforms with phase-2 capacitors of 1/3 times that of phase 1 provided the highest defibrillation efficacy (stored energy and voltage) compared with corresponding monophasic and biphasic waveforms with the same capacitors in both phases except for waveforms with a 30-microF phase-1 capacitor. In group 2, 10 biphasic waveforms from a combination of 2 phase-1 capacitor values (30 and 60 microF) and 5 phase-2 capacitor values (10, 20, 30, 40, and 50 microF) were tested. In this range, phase-2 capacitor size was more critical for the 30-microF phase-1 than for the 60-microF phase-1 capacitor. The optimal combinations of fully discharging capacitors for defibrillation were 60/20 and 60/30 microF. Conclusions-Phase-2 capacitor size plays an important role in reducing defibrillation energy in biphasic waveforms when 2 separate and fully discharging capacitors are used.

Background: Postganglionic vagal stimulation (PGVS) by short bursts of subthreshold current evokes release of acetylcholine from myocardial nerve terminals. PGVS applied to the atrioventricular node (AVN) slows nodal conduction. However, little is known about the ability of PGVS to control ventricular rate (VR) during atrial fibrillation (AF)., Methods and Results: To quantify the effects and establish the mechanism of PGVS on the AVN, AF was simulated by random high right atrial pacing in 11 atrial-AVN rabbit heart preparations. Microelectrode recordings of cellular action potentials (APs) were obtained from different AVN regions. Five intensities and 5 modes of PGVS delivery were evaluated. PGVS resulted in cellular hyperpolarization, along with depressed and highly heterogeneous intranodal conduction. Compact nodal AP exhibited decremental amplitude and dV/dt and multiple-hump components, and at high PGVS intensities, a high degree of concealed conduction resulted in a dramatic slowing of the VR. Progressive increase of PGVS intensity and/or rate of delivery showed a significant logarithmic correlation with a decrease in VR (P<0.001). Strong PGVS reduced the mean VR from 234 to 92 bpm (P<0.001). The PGVS effects on the cellular responses and VR during AF were fully reproduced in a model of direct acetylcholine injection into the compact AVN via micropipette., Conclusions: These studies confirmed that PGVS applied during AF could produce substantial VR slowing because of acetylcholine-induced depression of conduction in the AVN.