Ganglionated Plexi Stimulation Research Articles

Autonomic modulation impacts conduction velocity dynamics and wavefront propagation in the left atrium.

Atrial fibrosis and autonomic remodelling are proposed pathophysiological mechanisms in atrial fibrillation (AF). Their impact on conduction velocity (CV) dynamics and wavefront propagation was evaluated. Local activation times (LATs), voltage, and geometry data were obtained from patients undergoing ablation for persistent AF. LATs were obtained at three pacing intervals (PIs) in sinus rhythm (SR). LATs were used to determine CV dynamics and their relationship to local voltage amplitude. The impact of autonomic modulation- pharmacologically and with ganglionated plexi (GP) stimulation, on CV dynamics, wavefront propagation, and pivot points (change in wavefront propagation of ≥90°) was determined in SR. Fifty-four patients were included. Voltage impacted CV dynamics whereby at non-low voltage zones (LVZs) (≥0.5 mV) the CV restitution curves are steeper [0.03 ± 0.03 m/s ΔCV PI 600-400 ms (PI1), 0.54 ± 0.09 m/s ΔCV PI 400-250 ms (PI2)], broader at LVZ (0.2-0.49 mV) (0.17 ± 0.09 m/s ΔCV PI1, 0.25 ± 0.11 m/s ΔCV PI2), and flat at very LVZ (<0.2 mV) (0.03 ± 0.01 m/s ΔCV PI1, 0.04 ± 0.02 m/s ΔCV PI2). Atropine did not change CV dynamics, while isoprenaline and GP stimulation resulted in greater CV slowing with rate. Isoprenaline (2.7 ± 1.1 increase/patient) and GP stimulation (2.8 ± 1.3 increase/patient) promoted CV heterogeneity, i.e. rate-dependent CV (RDCV) slowing sites. Most pivot points co-located to RDCV slowing sites (80.2%). Isoprenaline (1.3 ± 1.1 pivot increase/patient) and GP stimulation (1.5 ± 1.1 increase/patient) also enhanced the number of pivot points identified. Atrial CV dynamics is affected by fibrosis burden and influenced by autonomic modulation which enhances CV heterogeneity and distribution of pivot points. This study provides further insight into the impact of autonomic remodelling in AF.

PO-01-005 GANGLIONATED PLEXI MEDIATED BRADYCARDIA RESPONSES: A PRE-CLINICAL STUDY OF DIFFERENCES BETWEEN PULSED FIELD AND RADIOFREQUENCY ABLATION IN THE LEFT ATRIUM

During left atrial catheter ablation procedures, the peri-atrial neural network of ganglionated plexi (GP) can be affected by the ablative energy. Bradycardic responses (BR) from GP stimulation have been reported during both radiofrequency (RF) and pulsed field (PF) ablation procedures. To assess differences in BR between RF and PF during canine left atrial ablation. Healthy canines (n=14) underwent transeptal access under general anesthesia. A multielectrode spherical array catheter (Globe PF System; Kardium Inc., Canada) capable of both cardiac mapping and ablation with either RF or PF was deployed in the left atrium. For each application, electroanatomic maps with ostial tags, contact maps based on blood flow detection, and animated voltage maps were created to help verify isolation. Either temperature-controlled RF ablation (63°C for 3 minutes) or PF ablation (1.7-1.8 kV) was used to circumferentially isolate two PVs/animal and create a linear and focal lesion along the posterior wall and roof of the left atrium. GP stimulation as evidenced by BR was recorded if either sinus bradycardia or AV block was noted during and/or immediately after the pulse train (Figure). A total of 11 and 3 animals underwent PF and RF ablation, respectively. All ablations were successfully delivered to all locations without adverse events. Of the animals treated with RF, none (0 of 3) displayed any evidence of GP stimulation at any locations. All animals treated with PF showed evidence of GP stimulation: all animals (11 of 11,100%) exhibited BR during ablation at the inferior common vein, with 6 of 10 (60%) animals demonstrating BR at the roof and posterior wall (Table). BR of less severity was noted during subsequent pulse trains but remained most frequent at the inferior common vein. Ganglionated plexi-mediated bradycardic responses occur with PF ablation, with evidence of some degree of stunning when repeated pulse trains are delivered. This pre-clinical model with ablation at this location will serve as a good model to further our understanding of this phenomenon. The lack of any bradycardic responses with RF either represents a lack of stimulation (perhaps because of the inability of the RF energy to reach the epicardial GPs, unlike the volumetric nature of the pulsed electrical fields) or, complete ablation without stimulation. Further work is needed to explore these differences.

PO-02-172 CONDUCTION VELOCITY AND CONDUCTION VELOCITY DYNAMICS IN THE LEFT ATRIUM ARE IMPACTED BY STRUCTURAL AND AUTONOMIC MODULATION AND SITES OF CONDUCTION VELOCITY HETEROGENEITY CORRELATE TO RE-ENTRY ACTIVITY IN ATRIAL FIBRILLATION

Structural and autonomic remodelling is proposed to drive atrial fibrillation (AF). Conduction velocity (CV) heterogeneity predisposes cardiac tissue to re-entry mechanisms. The impact of structural and autonomic remodelling on CV dynamics and re-entry formation is unclear. Evaluate the impact structural and autonomic modulation has on CV dynamics and re-entry activity in AF. Local activation times (LATs), voltage and geometry data were obtained from 20 patients undergoing catheter ablation for persistent AF. LATs were obtained at 3 pacing intervals (PI) (600, 400 and 250ms) with pacing from two pacing sites. LATs were used to determine CV dynamics and their relationship to voltage using an automated algorithm. Relationship between sites of enhanced CV heterogeneity defined as rate dependent CV slowing (RDCV) sites (sites exhibiting CV difference (CVd) between PI=600ms and PI=250ms of ≥20% of the mean CVd seen between these PIs for that voltage zone) and re-entry activity in AF was evaluated. Re-entry activity was identified using an automated algorithm and defined as ≥1.5 rotations of 360 degrees. The impact of autonomic modulation on CV dynamics both pharmacologically and with ganglionated plexi stimulation was assessed. A total of 512,082 LAT and voltage points were analysed. Voltage impacts CV (1.36±0.98 nLVZ ≥0.5mV, 1.05±1.03 LVZ 0.2-0.49mV and 0.58±0.37 vLVZ <0.2mV) (Figure 1A-B) and CV dynamics, whereby at nLVZ the curves are steeper (0.03±0.02ms CVd PI 600-400ms, 0.54±1.1ms CVd PI 400-250ms), broader at LVZ (0.16±0.09ms CVd PI 600-400ms, 0.23±1.1ms CVd PI 400-250ms) and flat at vLVZ (0.04±0.01ms CVd PI 600-400ms, 0.05±0.02ms CVd PI 400-250ms) (Figure 1C). Per patient, 5.6±1.1 RDCV sites and 3.4±1.3 sites of re-entry activity were identified. Of the RDCV sites, 72.3% (81/112) correlated to 94.1% (64/68) of re-entry activity sites which were mainly confined to LVZs (59/68, 86.8%). Autonomic modulation affected the CV dynamic curves through increasing rate dependency slowing (Figure 1D). The number of RDCV sites identified were enhanced following autonomic modulation (3.4±1.2 increase per patient). CVs and CV dynamics are impacted by structural remodelling and are influenced by autonomic modulation which enhances CV heterogeneity. CV heterogeneity sites correlate to re-entry activity in AF. Assessment of CV dynamics and heterogenity may help to determine the mechanistic importance of LVZs.

PV Isolation Using a Spherical Array PFA Catheter: Preclinical Assessment and Comparison to Radiofrequency Ablation

BackgroundA multielectrode spherical array catheter capable of single-shot mapping and ablation has been introduced. ObjectivesThis study sought to compare the efficacy and safety of circumferential, linear, and focal ablation using either microsecond pulsed field (PF) and radiofrequency (RF) ablation in preclinical model. MethodsUnder general anesthesia, a 122 gold-plated multielectrode array was introduced into the left atrium. Twenty-nine canines underwent isolation of two pulmonary veins (PVs), with linear and focal left atrial ablation with both RF (n = 12) and PF (n = 17). PF was also delivered within the superior vena cava and atop the esophagus in three swine. Animals were sacrificed acutely (immediately for RF [6 of 12] and 3 days for PF [6 of 17]) and the remaining (n = 17) at 14 to 30 days. Detailed necropsy and histopathology were performed. ResultsAll PVs were acutely (58 of 58) and durably (34 of 34) isolated and exhibited wide confluent lesions. Lesions were transmural for 97% to 100% of sections with depths of 2.5 to 3.4 mm and 2.5 to 3.5 mm in the acute and chronic cohorts, respectively. Linear and focal lesions displayed transmurality rates of 85% to 100% with depths of 3.5 millimeters to 4.2 millimeters in the acute cohort. In the chronic cohorts, linear lesions created with RF, PF+RF, and PF had no significant differences in depth (3.5 ± 1.8 mm, 4.0 ± 1.4 mm, and 3.9 ± 0.9 mm) or transmurality (83.3%, 100%, and 80%). Current of injury was seen on local unipolar electrogram immediately after PF and RF, and this occurred to a wider extent with PF. PF but not RF elicited bradycardia from ganglionated plexi stimulation. There were no instances of phrenic palsy, venous stenosis, esophageal damage, or thromboembolism. ConclusionsCircumferential, linear, and focal mapping and ablation can be achieved with this novel catheter using both PF and RF, with excellent efficacy and safety.

1094 MULTIVESSEL CORONARY ARTERY SPASM TRIGGERED BY GANGLIONATED PLEXI STIMULATION DURING ATRIAL FIBRILLATION RADIOFREQUENCY CATHETER ABLATYION: A CASE REPORT

Abstract Background Atrial fibrillation is the most common sustained cardiac arrhythmia in adults and it is associated with a high burden of mortality and morbidity worldwide. Atrial fibrillation could be managed with rate-control or rhythm-control strategies. The latter is increasingly used to improve symptoms and prognosis in selected patients, especially after the development of catheter ablation. Although this technique is generally considered safe, it is not free from rare but life-threatening procedure-related adverse events. Among these, coronary artery spasm is an uncommon but potentially fatal complication that requires immediate diagnosis and treatment. Case summary We report a case of severe multivessel coronary artery spasm triggered by ganglionated plexi stimulation during pulmonary vein isolation with radiofrequency catheter ablation in a patient with persistent atrial fibrillation, promptly resolved after intracoronary nitrate administration. Discussion Although rare, coronary artery spasm is a serious complication of atrial fibrillation catheter ablation. Immediate invasive coronary angiography is key for both diagnosis confirmation and treatment of such dangerous condition. As the number of invasive procedures increases, it is important that both interventional and general cardiologists are aware of possible procedure-related adverse events.

Location of Parasympathetic Innervation Regions From Electrograms to Guide Atrial Fibrillation Ablation Therapy: An in silico Modeling Study.

The autonomic nervous system (ANS) plays an essential role in the generation and maintenance of cardiac arrhythmias. The cardiac ANS can be divided into its extrinsic and intrinsic components, with the latter being organized in an epicardial neural network of interconnecting axons and clusters of autonomic ganglia called ganglionated plexi (GPs). GP ablation has been associated with a decreased risk of atrial fibrillation (AF) recurrence, but the accurate location of GPs is required for ablation to be effective. Although GP stimulation triggers both sympathetic and parasympathetic ANS branches, a predominance of parasympathetic activity has been shown. This study aims was to develop a method to locate atrial parasympathetic innervation sites based on measurements from a grid of electrograms (EGMs). Electrophysiological models representative of non-AF, paroxysmal AF (PxAF), and persistent AF (PsAF) tissues were developed. Parasympathetic effects were modeled by increasing the concentration of the neurotransmitter acetylcholine (ACh) in randomly distributed circles across the tissue. Different circle sizes of ACh and fibrosis geometries were considered, accounting for both uniform diffuse and non-uniform diffuse fibrosis. Computational simulations were performed, from which unipolar EGMs were computed in a 16 × 1 6 electrode mesh. Different distances of the electrodes to the tissue (0.5, 1, and 2 mm) and noise levels with signal-to-noise ratio (SNR) values of 0, 5, 10, 15, and 20 dB were tested. The amplitude of the atrial EGM repolarization wave was found to be representative of the presence or absence of ACh release sites, with larger positive amplitudes indicating that the electrode was placed over an ACh region. Statistical analysis was performed to identify the optimal thresholds for the identification of ACh sites. In all non-AF, PxAF, and PsAF tissues, the repolarization amplitude rendered successful identification. The algorithm performed better in the absence of fibrosis or when fibrosis was uniformly diffuse, with a mean accuracy of 0.94 in contrast with a mean accuracy of 0.89 for non-uniform diffuse fibrotic cases. The algorithm was robust against noise and worked for the tested ranges of electrode-to-tissue distance. In conclusion, the results from this study support the feasibility to locate atrial parasympathetic innervation sites from the amplitude of repolarization wave.

I Impact of Atrial Fibrillation on the Vagal Response to Ganglionated Plexi Stimulation: Comparison Between Patients with and without Atrial Fibrillation

I Impact of Atrial Fibrillation on the Vagal Response to Ganglionated Plexi Stimulation: Comparison Between Patients with and without Atrial Fibrillation

Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity: In silico modeling study.

BackgroundThe role of the autonomic nervous system (ANS) on atrial fibrillation (AF) is difficult to demonstrate in the intact human left atrium (LA) due to technical limitations of the current electrophysiological mapping technique. We examined the effects of the ANS on the initiation and maintenance of AF by employing a realistic in silico human left atrium (LA) model integrated with a model of ganglionated plexi (GPs).MethodsWe incorporated the morphology of the GP and parasympathetic nerves in a three-dimensional (3D) realistic LA model. For the model of ionic currents, we used a human atrial model. GPs were stimulated by increasing the IK[ACh], and sympathetic nerve stimulation was conducted through a homogeneous increase in the ICa-L. ANS-induced wave-dynamics changes were evaluated in a model that integrated a patient’s LA geometry, and we repeated simulation studies using LA geometries from 10 different patients.ResultsThe two-dimensional model of pulmonary vein (PV) cells exhibited late phase 3 early afterdepolarization-like activity under 0.05μM acetylcholine (ACh) stimulation. In the 3D simulation model, PV tachycardia was induced, which degenerated to AF via GP (0.05μM ACh) and sympathetic (7.0×ICa-L) stimulations. Under sustained AF, local reentries were observed at the LA-PV junction. We also observed that GP stimulation reduced the complex fractionated atrial electrogram (CFAE)-cycle length (CL, p<0.01) and the life span of phase singularities (p<0.01). GP stimulation also increased the overlap area of the GP and CFAE areas (CFAE-CL≤120ms, p<0.01). When 3 patterns of virtual ablations were applied to the 3D AF models, circumferential PV isolation including the GP was the most effective in terminating AF.ConclusionCardiac ANS stimulations demonstrated triggered activity, automaticity, and local reentries at the LA-PV junction, as well as co-localized GP and CFAE areas in the 3D in silico GP model of the LA.

Autonomic Modulation by Electrical Stimulation of the Parasympathetic Nervous System: An Emerging Intervention for Cardiovascular Diseases

The cardiac autonomic nervous system has been known to play an important role in the development and progression of cardiovascular diseases. Autonomic modulation by electrical stimulation of the parasympathetic nervous system, which increases the parasympathetic activity and suppresses the sympathetic activity, is emerging as a therapeutic strategy for the treatment of cardiovascular diseases. Here, we review the recent literature on autonomic modulation by electrical stimulation of the parasympathetic nervous system, including vagus nerve stimulation, transcutaneous auricular vagal stimulation, spinal cord stimulation, and ganglionated plexi stimulation, in the treatment of heart failure, atrial fibrillation, and ventricular arrhythmias.

Low-intensity Atrial Ganglionated Plexi Stimulation Decreases the Serum Level of Inflammatory Factors in Canine

Activation of efferent vagus fibers exerts an anti-inflammatory role, a mechanism known as the cholinergic anti-inflammatory pathway. We hypothesised that stimulation of atrial ganglionated plexi (GP) may also be anti-inflammatory. Six-hour low-intensity GP stimulation was performed in eight dogs and the serum levels of acetylcholine (Ach), C reactive protein (CRP), interleukin-6 (IL-6), high-mobility group box 1 (HMGB1) were determined with enzyme-linked immunosorbent assay kits. The serum level of acetylcholine was significantly increased (P<0.05) while the serum levels of inflammatory factors of C reactive protein, interleukin-6 and high-mobility group box 1 were markedly decreased after six-hour GP stimulation (all P<0.05). These results suggest that GP stimulation exerts an anti-inflammatory role and might be a therapeutic option for inflammatory heart diseases.

Low level tragus nerve stimulation is a non-invasive approach for anti-atrial fibrillation via preventing the loss of connexins

Atrial fibrillation (AF) is the most common cardiac arrhythmia, but the mechanism of AF maintenance remains unclear. It has been found that gap junctional remodeling (connexin expression is downregulated and distributed) is closely associated with AF maintenance [ [1] Van der Velden H.M. Ausma J. Rook M.B. Hellemons A.J. van Veen T.A. Allessie M.A. Jongsma H.J. Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat. Cardiovasc. Res. 2000; 46: 476-486 Crossref PubMed Scopus (214) Google Scholar ]. Autonomic nervous system stimulation can exert anti-arrhythmia effects [ 2 Thunsiri K. Shinlapawittayatorn K. Chinda K. Palee S. Surinkaew S. Chattipakorn S.C. KenKnight B.H. Chattipakorn N. Application of vagus nerve stimulation from the onset of ventricular fibrillation to post-shock period improves defibrillation efficacy. Int. J. Cardiol. 2014; 176: 1030-1032 Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar , 3 He B. Lu Z. He W. Huang B. Jiang H. Similar effects of vagus nerve stimulation and atrial ganglionated plexi stimulation on ventricular effective refractory period and action potential duration in canine. Int. J. Cardiol. 2013; 168: 5116-5118 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ]. Recently, we reported that cervical low level vagal nerve stimulation (LL-VNS) could suppress AF induced high-frequency stimulation [ [4] Yu L. Scherlag B.J. Li S. Sheng X. Lu Z. Nakagawa H. Zhang Y. Jackman W.M. Lazzara R. Jiang H. Po S.S. Low-level vagosympathetic nerve stimulation inhibits atrial fibrillation inducibility: direct evidence by neural recordings from intrinsic cardiac ganglia. J. Cardiovasc. Electrophysiol. 2011; 22: 455-463 Crossref PubMed Scopus (104) Google Scholar ] and then we developed a non-invasive approach, low level tragus nerve stimulation (LL-TS), and found that it had the same effect on suppressing AF [ [5] Yu L. Scherlag B.J. Li S. Fan Y. Dyer J. Male S. Varma V. Sha Y. Stavrakis S. Po S.S. Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve: a noninvasive approach to treat the initial phase of atrial fibrillation. Heart Rhythm. 2013; 10: 428-435 Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar ]. However, whether LL-TS could regulate Cx40 and Cx43 to suppress AF remains unknown. We hypothesized that LL-TS exerted anti-atrial fibrillatory effect via the downregulation of atrial Cx40 and Cx43.

Effects of renal sympathetic denervation on the atrial electrophysiology in dogs with pacing-induced heart failure.

Heart failure (HF) and atrial fibrillation (AF) are associated with sympathetic activation. Renal sympathetic denervation (RSD) can suppress AF vulnerability. The impact of RSD on atrial electrophysiology in experimental HF is unclear. Twenty-two beagles were randomized into control, HF, and HF + RSD groups. Control dogs were implanted cardiac pacemakers without pacing. Dogs in the HF group underwent right ventricular pacing for 3 weeks at 240 beats/min to induce HF. The dogs in the HF + RSD group received RSD and underwent the same HF-inducing procedure. The P-wave dispersion was higher in HF dogs than in the control and HF + RSD dogs (19 ± 3.1 ms vs 13 ± 2.3 ms, 15 ± 2.9 ms, P = 0.04). Conduction time within the interatrium was significantly longer in the HF dogs than that in the control and HF + RSD dogs (39 ± 4 ms vs 31 ± 3 ms, 33 ± 4 ms; P = 0.03). Window of vulnerability (WOV) of AF was widened in the HF dogs than in the HF + RSD dogs (37 ± 5 ms vs 14 ± 3 ms; P < 0.01), while AF could not be induced (WOV = 0) in the control dogs during S1 S2 stimulation. The voltage in the threshold for AF inducibility was lower during ganglionated plexi stimulation in the HF dogs than in the control and HF + RSD dogs (1.8 ± 0.6 V vs 2.5 ± 0.6 V, 2.4 ± 0.4 V; P = 0.04). RSD could reverse the atrial electrical remodeling and decrease AF inducibility in dogs with pacing-induced HF.

The independent role of the aortic root ganglionated plexi in the initiation of atrial fibrillation: An experimental study

The major atrial ganglionated plexi (GP) can initiate atrial fibrillation alone without any contribution from the extrinsic cardiac nervous system. However, if stimulation of the ventricular GP, especially the aortic root GP, can provoke atrial fibrillation (AF) alone is unknown. Our study was designed to investigate the independent role of aortic root GP activity in the initiation of AF. In 10 Langendorff-perfused canine hearts, the atrial effective refractory period, pulmonary vein effective refractory period, and percentage of AF induced were measured at baseline and during aortic root GP stimulation. Stimulation of the aortic root GP shortened the atrial effective refractory period from 128 ± 10 ms atbaseline to 103 ± 15 ms (P<.05) and shortened the pulmonary vein effective refractory period from 139± 14 ms to 114 ± 15 ms (P<.05). Furthermore, the percentage of AF induced in the 10 isolated hearts increased from 10% at baseline to 90% during aortic root GP stimulation (P<.05). In Langendorff-perfused canine hearts, stimulation of the aortic root GP provokes AF in theabsence of any extrinsic cardiac nerve activity. The aortic root GP is an important element in the intrinsicneuronal loop that can increase the risk of AF in isolated heart models.

Atrial ganglionated plexi stimulation may be an effective therapeutic tool for the treatment of heart failure

An autonomic imbalance, i.e., increased sympathetic tone and/or decreased parasympathetic tone is a critical characteristic of heart failure, which is associated with progressive ventricular remodeling, ventricular arrhythmia generation and disease progression. Increasing cardiac parasympathetic tone by vagus nerve stimulation has been shown to significantly improve heart failure symptoms, hemodynamics, left ventricular function and quality of life. However, cervical surgery is needed to position vagal stimulation electrode and vagus nerve stimulation may also cause some undesired side effects. Our recent studies showed that ablation of the main atrial ganglionated plexi (GP) facilitated the occurrence of ventricular arrhythmias in acute myocardial ischemic heart while low-intensity atrial GP stimulation inhibited the occurrence of ventricular arrhythmias during acute myocardial ischemia and ischemia reperfusion. Based on these results, we hypothesize that atrial GP stimulation may ameliorate autonomic dysfunction in heart failure, inhibit heart failure progression and improve heart failure prognosis.

Similar effects of vagus nerve stimulation and atrial ganglionated plexi stimulation on ventricular effective refractory period and action potential duration in canine

Cervical vagus nerves and atrial ganglionated plexi (GP) serve as the main extrinsic and intrinsic cardiac parasympathetic nervous systems [1], respectively. Atrial GP have been found to be concentrated within epicardial fat pads. Although atrial GP are traditionally considered as relay stations that merely transmit central parasympathetic impulses to the heart, recent studies indicated that GP included not only parasympathetic postganglionic neurons but also sympathetic neurons and the innervation by a host of neurochemically non-cholinergic inputs [2], going well beyond cholinergic efferent neuronal relay stations.

ASSA13-03-7 Renal Sympathetic Denervation Changes the Distribution of Atrial Substrate and Inhibites the Inducibility of Atrial Fibrillation

Objective Whether renal sympathetic denervation has effect on changes of atrial substrate and inducilibity of atrial fibrillation is unknown. The purpose of this study was to determine the effect of renal denervation on the inducibility atrial fibrillation. Methods Thirteen dogs were randomly divided into control group (7 dogs) and renal artery ablation group (6 dogs). In control group, at first, atrial fibrillation was induced by anterior right ganglionated plexi stimulation. Then, rapid atrial pacing was performed for 7 hours. Atrial effective refractory period and atrial fibrillation were measured each hour. In renal artery ablation group, after renal artery ablation, dogs were raised for 6 weeks. After that, the procedure of pacing and electrophysiological measurement was same as in the control group. Results The voltage in the sinus rate slowing response and the threshold of inducilibity atrial fibrillation increased during ganglionated plexi stimulation after renal artery ablation (3.5 ± 1.6V vs 1.6 ± 0.3V; 5.1V ± 1.0V vs 2.1V ± 0.7V, P = 0.03). Induced number of times and duration of atrial fibrillation was higher in control group than that in renal artery ablation group after cessation of pacing. Levels of ANP in right atrium and densities of Cx43 were lower in renal artery ablation group than that in control group (ANP: 220.5 ± 37.6 pg/mg vs 164.4 ± 22.0 pg/mg, P = 0.02; Cx43: 0.52, 0.63, 0.87 vs 1, 1.02, 1.91, P Conclusions Renal sympathetic denervation results in changes of atrial substrate and markedly decrease the inducilibity of atrial fibrillation by inhibiting activity of renin-angiotensin-aldosterone system.

The effects of atrial ganglionated plexi stimulation on ventricular electrophysiology in a normal canine heart

Atrial ganglionated plexi (GP) have been shown to modulate atrial electrophysiology and play an important role in atrial fibrillation initiation and maintenance. The purpose of this study was to investigate the effects of atrial GP stimulation (GPS) on ventricular refractoriness, restitution properties and electrical alternans. In 12 anesthetized dogs, two multiple electrode catheters were sutured at left and right ventricular free walls for recording. Monophasic action potentials were recorded from six epicardial ventricular sites. Ventricular effective refractory period (ERP), action potential duration (APD) restitution properties and APD alternans were measured at baseline and during GPS. Compared with baseline, GPS significantly prolonged ventricular ERP and APD at all sites and decreased their spatial dispersions (P < 0.05 for all). GPS also significantly flattened ventricular restitution curves and decreased the maximal slope of restitution curves at each site (P < 0.05 for all). APD alternans occurred at shorter pacing cycle length at each site during GPS when compared with baseline (P < 0.05 for all). GPS prolonged ventricular ERP, decreased the slope of restitution curves and delayed APD alternans, indicating that GPS may exert a protective role for ventricular arrhythmias.

Effects of low-intensity atrial ganglionated plexi stimulation on ventricular electrophysiology and arrhythmogenesis

Atrial ganglionated plexi (GP) have been shown to modulate sinus rate, atrioventricular conduction and atrial electrophysiology. The aim of this study was to investigate the effect of low-intensity GP stimulation (GPS) on ventricular electrophysiological properties in normal heart and on ventricular arrhythmogenesis after acute myocardial ischemia (AMI) in canine. Thirty-nine dogs were assigned into the normal heart group (n=12) and the acute myocardial ischemia (AMI) group (n=27, 12 in control and 15 in low-intensity GPS). In the normal heart group, ventricular effective refractory period (ERP), dynamic restitution and electrical alternans were measured at baseline and after 6-hour low-intensity GPS. In the AMI group, the incidence of ventricular arrhythmias was determined during 1-hour recording after AMI was induced. In the normal heart, 6-hour low-intensity GPS significantly prolonged ventricular ERP and action potential duration (APD) at each site (all P<0.05) but did not change their spatial dispersions when compared with baseline. Low-intensity GPS also caused an upward shift of ventricular restitution curves in each site but did not change the slope of restitution curves. APD alternans after low-intensity GPS occurred at longer pacing cycle length at each site when compared with baseline (all P<0.05). In the AMI heart, the incidence of ventricular arrhythmias in low-intensity GPS group was significantly lower than that in control group (P<0.05). Low-intensity GPS induces no increase in the risk of ventricular arrhythmias in the normal heart as well as protects against ventricular arrhythmogenesis during AMI.

Inhibition of atrial fibrillation by low-level vagus nerve stimulation: the role of the nitric oxide signaling pathway

We examined the role of the phosphatidylinositol-3 kinase (PI3K)/nitric oxide (NO) signaling pathway in low-level vagus nerve stimulation (LLVNS)-mediated inhibition of atrial fibrillation (AF). In 17 pentobarbital anesthetized dogs, bilateral thoracotomies allowed the attachment of electrode catheters to the superior and inferior pulmonary veins and atrial appendages. Rapid atrial pacing (RAP) was maintained for 6 h. Each hour, programmed stimulation was used to determine the window of vulnerability (WOV), a measure of AF inducibility, at all sites. During the last 3 h, RAP was overlapped with right LLVNS (50 % below that which slows the sinus rate). In group 1 (n = 7), LLVNS was the only intervention, whereas in groups 2 (n = 6) and 3 (n = 4), the NO synthase inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME) and the PI3K inhibitor wortmannin, respectively, were injected in the right-sided ganglionated plexi (GP) during the last 3 h. The duration of acetylcholine-induced AF was determined at baseline and at 6 h. Voltage-sinus rate curves were constructed to assess GP function. LLVNS significantly decreased the acetylcholine-induced AF duration by 8.2 ± 0.9 min (p < 0.0001). Both L-NAME and wortmannin abrogated this effect. The cumulative WOV (the sum of the individual WOVs) decreased toward baseline with LLVNS (p < 0.0001). L-NAME and wortmannin blunted this effect during the fifth (L-NAME only, p < 0.05) and the sixth hour (L-NAME and wortmannin, p < 0.05). LLVNS suppressed the ability of GP stimulation to slow the sinus rate, whereas L-NAME and wortmannin abolished this effect. The anti-arrhythmic effects of LLVNS involve the PI3K/NO signaling pathway.

049 The role of the neural networks in identification and ablation of pulmonary vein ectopic triggers

IntroductionThe cardiac neural network comprises ganglionated plexi (GP) adjacent to each pulmonary vein (PV) which can trigger AV block and PV ectopy. We hypothesised that AV block in response to...