Inferior Vena Cava as a Trigger for Paroxysmal Atrial Fibrillation: Incidence, Characteristics, and Implications.

BACKGROUND: Identifying nonpulmonary vein triggers during atrial fibrillation (AF) ablation is of great importance. Currently, there are limited data on AF triggered by the inferior vena cava (IVC). OBJECTIVES: This study was performed to investigate the incidence, characteristics, and implications of IVC triggers for AF. METHODS: A total of 661 patients who underwent initial paroxysmal AF ablation were included. After pulmonary vein isolation, ectopic beats that triggered AF were further studied. Activation mapping and angiography were performed to confirm the location of ectopic origin. Electrocardiographic analysis of the ectopic P-wave (P'-wave) was performed. RESULTS: Six patients (0.91%) with AF triggered by the IVC were confirmed. The mean distance from the earliest activation site to the IVC ostium was 6.8 ± 2.5 mm (5.2 to 11.2 mm). Furthermore, the arrhythmogenic foci within the IVC were all located at the apical hemisphere of the IVC (3 at the septal side and 3 at the anterior side). A total of 2.3 ± 0.5 applications of radiofrequency energy were delivered to eliminate IVC triggers. The mean duration of the P' wave was 91.2 ± 11.2 milliseconds (81 to 108 milliseconds), which was narrower than that of the sinus P-wave (115.2 ± 19.3 milliseconds [87 to 139 milliseconds]; P = 0.002). Moreover, the configuration of all P' waves in the inferior leads was negative. During a mean follow-up period of 25.5 ± 7.3 months, all 6 patients remained arrhythmia free without antiarrhythmic drugs. CONCLUSIONS: IVC trigger, a rare but latent source of paroxysmal AF, could be identified and safely eliminated by focal radiofrequency ablation. Ectopic beats originating from the IVC presented with narrow P'-wave duration and negative P' waves in all inferior leads.

Blockade of NaV1.8 Increases the Susceptibility to Ventricular Arrhythmias During Acute Myocardial Infarction.

SCN10A/NaV1.8 may be associated with a lower risk of ventricular fibrillation in the setting of acute myocardial infarction (AMI), but if and by which mechanism NaV1.8 impacts on ventricular electrophysiology is still a matter of debate. The purpose of this study was to elucidate the contribution of NaV1.8 in ganglionated plexi (GP) to ventricular arrhythmias in the AMI model. Twenty beagles were randomized to either the A-803467 group (n = 10) or the control group (n = 10). NaV1.8 blocker (A-803467, 1 µmol/0.5 mL per GP) or DMSO (0.5 mL per GP) was injected into four major GPs. Ventricular effective refractory period, APD90, ventricular fibrillation threshold, and the incidence of ventricular arrhythmias were measured 1 h after left anterior descending coronary artery occlusion. A-803467 significantly shortened ventricular effective refractory period, APD90, and ventricular fibrillation threshold compared to control. In the A-803467 group, the incidence of ventricular arrhythmias was significantly higher compared to control. A-803467 suppressed the slowing of heart rate response to high-frequency electrical stimulation of the anterior right GP, suggesting that A-803467 could inhibit GP activity. SCN10A/NaV1.8 was readily detected in GPs, but was not validated in ventricles by quantitative RT-PCR, western blot and immunohistochemistry. While SCN10A/NaV1.8 is detectible in canine GPs but not in ventricles, blockade of NaV1.8 in GP increases the incidence of ventricular arrhythmias in AMI hearts. Our study shows for the first time an influence of SCN10A/NaV1.8 on the regulation of ventricular arrhythmogenesis via modulating GP activity in the AMI model.

Functional properties of the superior vena cava (SVC)-aorta ganglionated plexus: evidence suggesting an autonomic basis for rapid SVC firing.

INTRODUCTION: the mechanism underlying spontaneous rapid superior vena cava (SVC) firing that initiates atrial fibrillation (AF) remains poorly understood. We investigated the role of the SVC-aorta-ganglionated plexus (SVC-Ao-GP) in AF initiated by rapid firing from the SVC. METHODS AND RESULTS: in 42 dogs, a circular catheter was positioned above the SVC-atrial junction. Multielectrode catheters were sutured on atria, atrial appendages and pulmonary veins. The effective refractory period (ERP) and window of vulnerability (WOV) for AF were measured at all sites in the baseline state, during cervical vagosympathetic trunk stimulation and during SVC-Ao-GP stimulation, before and after SVC-Ao-GP ablation. AF inducibility was also assessed by delivering high-frequency stimulation (HFS) within myocardial refractory period to the SVC before and after SVC-Ao-GP ablation. HFS applied to the SVC-Ao-GP slowed the sinus rate and/or atrioventricular conduction. HFS of the SVC-Ao-GP induced more significant shortening of ERP and a greater increase in WOV at the SVC than other sites. Ablation of the SVC-Ao-GP significantly increased the baseline ERP and decreased the baseline WOV only at the SVC. AF induced at the SVC by HFS during refractoriness was eliminated by ablation of the SVC-Ao-GP but was not altered by ablation of the 4 major atrial GP. Direct injection of acetylcholine into the SVC-Ao-GP initiated rapid firing from the SVC in every case. CONCLUSIONS: the SVC-Ao-GP preferentially modulates the electrophysiological function of the SVC sleeves and may contribute to rapid firing from the SVC.

Autonomic elements within the ligament of Marshall and inferior left ganglionated plexus mediate functions of the atrial neural network.

OBJECTIVES: We sought to systematically investigate the role of the ligament of Marshall (LOM) and inferior left ganglionated plexi (ILGP) in modulating electrophysiological functions. METHODS: The following structures were exposed in 36 dogs: (1) LOM, (2) superior left GP (SLGP) near the junction of left superior pulmonary vein (LSPV) and left atrium, (3) ILGP near the left inferior pulmonary vein-atrial junction, (4) anterior right GP (ARGP) near the sino-atrial node, and (5) inferior right GP (IRGP) at the junction of inferior vena cava and atria. High frequency stimulation (HFS; 0.6-8.0 V, 20 Hz, 0.1 msec in duration) was applied to the LOM, SLGP, ILGP, ARGP, IRGP, or vagosympathetic trunk. Ventricular rate (VR) during atrial fibrillation (AF) was compared before and after ablation of GP in different sequences. RESULTS: ARGP + ILGP ablation but not ARGP ablation alone eliminated the VR slowing response induced by LOM stimulation, suggesting that all the autonomic innervation from the LOM to AV node passes the ILGP. LOM ablation attenuated the VR slowing response caused by SLGP or left vagosympathetic stimulation, suggesting that LOM modulates the autonomic innervation between the AV node and the left vagosympathetic trunk or SLGP. ARGP attenuated while ARGP + ILGP ablation eliminated the VR slowing response induced by left vagosympathetic stimulation, suggesting that both ARGP and ILGP modulate the AV nodal innervation of the extrinsic and intrinsic cardiac autonomic nervous system (ANS). CONCLUSION: The LOM and ILGP function as the "integration centers" that modulate the autonomic interactions between extrinsic and intrinsic cardiac ANS on AV nodal function.

An acute model for atrial fibrillation arising from a peripheral atrial site: evidence for primary and secondary triggers.

BACKGROUND: We previously demonstrated that acetylcholine (Ach) injected into cardiac ganglionated plexi (GP) causes pulmonary vein (PV) ectopy initiating atrial fibrillation (AF). OBJECTIVE: To determine the effects of Ach applied at non-PV sites. METHODS: Overall, 54 dogs were anesthetized with Na-pentobarbital. A right and left thoracotomy allowed the placement of multielectrode catheters to record from the superior PVs, mid portion of the atrium and the atrial appendages (AA). A monophasic action potential (MAP) was recorded from the AA. Ach (1, 10, 100 mM) was applied sequentially to the AA. RESULTS: In 19 of 26 animals, Ach 100 mM on the right (n = 15) or left (n = 4) AA induced focal, sustained AF (>or=10 minutes) with rapid regular firing (cycle length = 37 +/- 7 ms) at the AA. A clamp with teeth placed across the AA caused arrest in the AA. However, AF was sustained only when PV sites adjacent to the GP manifested complex fractionated atrial electrograms (CFAE). Clamping the AA prior to Ach (100 mM) application resulted in focal AF arising at the PVs but not at the AA. When a clamp without teeth was applied prior to Ach application, no AF at either AA or PV site could be induced. CONCLUSION: Isolation of the focal AF at the AA (primary trigger) by clamping caused cessation of activity in the AA, but AF continued due to secondary triggers arising from PVs. The possible mechanism(s) responsible for these findings are discussed, and various ancillary experiments (n = 28) were added to help elucidate mechanisms.

Inducibility of atrial and ventricular arrhythmias along the ligament of marshall: role of autonomic factors.

BACKGROUND: The mechanism(s) underlying atrial fibrillation (AF) initiation along the ligament of Marshall (LOM) remains controversial. OBJECTIVES: We sought to examine the role of the autonomic nervous system in arrhythmogenesis along the LOM. METHODS: In 31 anesthetized dogs, a left thoracotomy exposed the LOM. During atrial pacing, high-frequency stimulation (HFS: 200 Hz, 0.1 ms pulse width, 40 ms duration, 0.6-12 V) was delivered during atrial refractoriness to different sites of LOM (LOM(CS)= near coronary sinus; LOM(LIPV)= near left inferior pulmonary vein; LOM(LS-LIPV)= between LIPV and left superior pulmonary vein (LSPV); LOM(LSPV)= near LSPV). HFS was repeated after intravenous administration of esmolol (1 mg/kg; n = 9) or atropine (2 mg; n = 12). Norepinephrine (10(-7) M, 0.4 cc) was injected into LOM(LSPV) (n = 5). RESULTS: The median voltages for HFS to induce AF were 3.2 V, 3.2 V, 8.0 V*(,double dagger), and 12 V*(,double dagger) at LOM(CS), LOM(LIPV), LOM(LS-LIPV), and LOM(LSPV), respectively (*P < 0.01, compared with LOM(CS) and double dagger P < 0.01, compared with LOM(LIPV)). Esmolol or atropine markedly increased the threshold for AF induction. Ventricular tachycardias (VT) and accelerated junctional rhythm were induced in 8 of 12 and 6 of 12 dogs after atropine administration, respectively. Sustained VT occurred within minutes in 5 of 5 dogs receiving norepinephrine injection into the LOM(LSPV.) CONCLUSION: HFS induced AF along LOM with a gradient of stimulation thresholds from LOM(CS) (lowest) toward LOM(LSPV) (highest). This response was inhibited by esmolol or atropine. These data suggest an autonomic basis for AF initiation in LOM, and both sympathetic and parasympathetic neural elements play an important role in AF initiation. Hyperactivity of the sympathetic neural elements in LOM may be crucial in the initiation of ventricular tachyarrhythmias.

Autonomic mechanism for complex fractionated atrial electrograms: evidence by fast fourier transform analysis.

INTRODUCTION: The mechanism(s) underlying complex fractionated atrial electrograms (CFAE) is not well understood. We hypothesized that CFAE may be caused by enhanced activity of the intrinsic cardiac autonomic nervous system. METHODS AND RESULTS: In 35 anesthetized dogs, via a right or left thoracotomy, sustained atrial fibrillation was induced by local application of acetylcholine (ACh; 10, 100 mM) to the surface of the atrial appendage (AA) or by injection of ACh (10 mM) into the ganglionated plexi (GP). Fast Fourier transform analysis was performed from recordings at AA, atrial sites near the AA, mid portion of the atrium, atrial sites near the GP, and the pulmonary veins. After AF was induced with ACh either by topical application to the AA or by direct injection into the GP, CFAE exhibited a significant gradient of progressively decreasing dominant frequency and incidence of CFAE (CFAE%) from the GP toward distant sites, while regularity index progressively decreased in the opposite direction. Ablation of GP markedly attenuated CFAE and eliminated these gradients. CONCLUSIONS: These results suggest CFAE may result from activation of the intrinsic cardiac autonomic nervous system in these animal models of sustained AF. Ablation of GP attenuates CFAE and eliminates the DF gradient.

[Incidence, risk factors and management of pericardial effusion post radiofrequency catheter ablation in patients with atrial fibrillations].

OBJECTIVE: Pericardial effusion (PE) is a major complication of atrial fibrillation ablation (AFB). We analyzed the incidence, risk factors and managements of PE post AFB (radiofrequency catheter ablation). METHODS: A total of 156 consecutive patients with AF [male 108, paroxysmal AF 114, (57.6 +/- 11.3) years], who underwent AFB guided by a three-dimensional mapping system (CARTO or CARTO-Merge, Biosense-Webster Inc., Diamond Bar, California) and a circular mapping catheter (Lasso, Biosense-Webster Inc., Diamond Bar, California), were included in this study. The ablation strategy included circumferential pulmonary veins isolation (CPVI), linear ablation and/or complex fractionated atrial electrograms (CFAEs) ablation. Electrophysiological data and vital signs of patients were recorded by a multiple physiological recorder (Prucka, GE Medical Systems) during ablation. Ablation process, sites, duration and other related factors were also recorded. Echocardiography and other examinations were performed for diagnosing and monitoring PE. RESULTS: CPVI were achieved in all 156 patients. Incidence of PE was 10.3% (16/156) post AFB. One patient developed acute cardiac tamponade and emergency drainage of the pericardial effusion was performed through a median sternotomy and patient recovered without complications during the 18 months follow-up. The rest 15 PE patients with small PE received outpatient care and no invasive treatment was needed and PE disappeared after 3 months in 6 patients and after 6 months in 9 patients. Univariate analysis showed that the composition of gender (P < 0.01), ablation in coronary sinus (CS, P = 0.026), ablation of CFAEs (P = 0.037) and superior vena cava (SVC, P = 0.041) were risk factors for PE. Logistic regression analysis showed that female gender [beta = 3.594, exp (b) = 36.4, 95% confidence interval (CI): 4.2 - 312.1, P = 0.001] and ablation in CS [beta = 2.419, exp (b) = 11.2, 95% CI: 1.0 - 124.6, P = 0.049] were independent risk factors for PE post AFB. CONCLUSIONS: PE is a common complication of AFB, female gender and ablation in CS were independent risk factors for PE. Most PE patients experienced spontaneous recovery but emergency treatment was needed for patient with cardiac tamponade.

Autonomic mechanism to explain complex fractionated atrial electrograms (CFAE).

OBJECTIVE: To simulate complex fractionated atrial electrograms (CFAE) during sustained atrial fibrillation (AF) in experimental animals. BACKGROUND: The mechanism(s) underlying CFAE has not been fully elucidated. METHODS: Twenty-two dogs were subjected to a right and/or left thoracotomy. A gauze patch soaked with acetylcholine (ACh) was placed on the right atrial appendage (RAA) to induce sustained AF. During AF, varying concentrations of ACh (1, 10, 100 mM) were "painted" on the RA where electrograms showed regular organized activity. In another six dogs, anterior right ganglionated plexi (ARGP) near the sino-atrial node and inferior right GP (IRGP) at the junction of inferior vena cava and atria were sequentially ablated. In five dogs, ACh was injected into ARGP to induce CFAE. RESULTS: During sustained AF, local "painting" with ACh 1 mM and 10 mM induced intermittent CFAE in 1 of 11 and 10 of 11 dogs, respectively. With 100 mM ACh, all 11 showed CFAE (two intermittent, nine continuous). In six other dogs, continuous CFAE induced by topical application of 100 mM ACh were markedly attenuated by ARGP + IRGP ablation. In another five of five dogs, ACh injection into ARGP induced a gradient of CFAE with the continuous CFAE always occurring near the ARGP and CFAE also occurring at left pulmonary vein-atrial junctions. During ARGP ablation, AF was terminated in all five dogs immediately after regularization of the rotor-like electrograms or continuous CFAE. CONCLUSIONS: This study demonstrates an autonomic basis for CFAE formation, suggesting that graded hyperactive states of the autonomic nervous system (ANS) may induce various types of CFAE observed clinically.

Interactive atrial neural network: Determining the connections between ganglionated plexi.

BACKGROUND: The electrophysiologic functions of the intrinsic cardiac autonomic nervous system (ANS) are not well understood. OBJECTIVES: The purpose of this study was to investigate the functional interactions between ganglionated plexi within the intrinsic cardiac ANS. METHODS: The hearts of 21 dogs were exposed via right and/or left thoracotomy to expose the (1) anterior right ganglionated plexi near the caudal end of the sinoatrial node, (2) inferior right ganglionated plexi at the junction of inferior vena cava and atria, and (3) superior left ganglionated plexi near the junction of left superior pulmonary vein and left pulmonary artery. Ganglionated plexi were stimulated at 0.6 to 8.0 V (square waves, 20 Hz, 0.1-ms duration). Sinus rate, AH interval during atrial pacing, and ventricular rate during atrial fibrillation were compared before and after ganglionated plexi stimulation and after their ablation. RESULTS: Anterior right ganglionated plexi stimulation induced significant AH prolongation and slowing of ventricular rate and sinus rate. When inferior right ganglionated plexi was ablated, slowing of sinus rate by anterior right ganglionated plexi stimulation was unaltered, but inhibition of AV conduction was eliminated. Superior left ganglionated plexi stimulation induced similar effects on sinus and AV nodal function, and sinus rate slowing was markedly attenuated by anterior right ganglionated plexi ablation. Ablation of both anterior right ganglionated plexi and inferior right ganglionated plexi eliminated AV conduction inhibition but not sinus rate slowing by superior left ganglionated plexi stimulation. CONCLUSION: This study provides functional evidence for the interconnections between ganglionated plexi to modulate sinus and AV nodal function, supporting clinical evidence that interconnections within the intrinsic cardiac ANS are critical elements in identifying the targets for atrial fibrillation ablation.

Thromboembolic event rate in patients with persistent or paroxysmal atrial fibrillation post circumferential pulmonary vein isolation: a single center experience in China.

BACKGROUND: Pulmonary-vein isolation (PVI) is currently used for the treatment of chronic and paroxysmal atrial fibrillation and a major risk of PVI is thromboembolism. The purpose of this study was to observe embolic event rate in patients with persistent or paroxysmal atrial fibrillation (AF) undergone PVI. METHODS: Circumferential PVI (CPVI) was performed in 64 consecutive patients with persistent AF (42 men, aged (60.0 +/- 9.1) years) and in 84 consecutive patients with paroxysmal AF (53 men, aged (61.4 +/- 9.3) years). Warfarin was administrated in all patients before ablation for at least 3 weeks ((5.2 +/- 2.6) weeks) and continued for at least 3 months post ablation with international normalized ratio (INR) of 2.0 - 3.0. During CPVI, intravenous heparin was given at a dose of 5000 - 8000 U or 75 - 100 U/kg, followed by 1000 U or 12 U/kg per hour. RESULTS: In patients with persistent AF, 1 patient developed embolic event during ablation and 3 patients developed embolic events after ablation. In contrast, no thromboembolic event was observed in patients with paroxysmal AF (4/64 vs 0/84, P = 0. 033). CONCLUSION: Thromboembolic event rate related to CPVI is significantly higher in patients with persistent AF than that in patients with paroxysmal AF.

Autonomic mechanism for initiation of rapid firing from atria and pulmonary veins: evidence by ablation of ganglionated plexi.

AIMS: Previous studies showed that autonomic activation by high-frequency electrical stimulation (HFS) during myocardial refractoriness evokes rapid firing from pulmonary vein (PV) and atria, both in vitro and in vivo. This study sought to investigate the autonomic mechanism underlying the rapid firings at various sites by systematic ablation of multiple ganglionated plexi (GP). METHODS AND RESULTS: In 43 mongrel dogs, rapid firing-mediated atrial fibrillation (AF) was induced by local HFS (200 Hz, impulse duration 0.1 ms, train duration 40 ms) to the PVs and atria during myocardial refractoriness. The main GP in the atrial fat pads or the ganglia along the ligament of Marshall (LOM) were then ablated. Ablation of the anterior right GP and inferior right GP significantly increased the AF threshold by HFS at the right atrium and PVs. The AF threshold at left atrium and PVs was significantly increased by ablation of the superior left GP and inferior left GP, and was further increased by ablation of the LOM. Ablation of left- or right-sided GP on the atria had a significant effect on contralateral PVs and atrium. Administration of esmolol (1 mg/kg) or atropine (1 mg) significantly increased AF threshold at all sites. CONCLUSION: HFS applied to local atrial and PV sites initiated rapid firing via activation of the interactive autonomic network in the heart. GP in either left side or right side contributes to the rapid firings and AF originating from ipsolateral and contralateral PVs and atrium. Autonomic denervation suppresses or eliminates those rapid firings.

Antifibrillatory properties of mivacurium in a canine model of atrial fibrillation.

The electrophysiologic actions of the competitive neuromuscular blocker mivacurium (0.05-0.8 mg/kg IV; N = 10) and atropine sulfate [0.01-0.16 mg/Kg intravenously (IV), N = 6] were determined under control conditions, during right vagus nerve stimulation, and during anterior right ganglionated plexus stimulation. Both drugs suppressed shortening of right atrial monophasic action potential (MAP) duration, right atrial refractoriness, and right superior pulmonary vein sleeve refractoriness produced by vagus nerve or ganglionated plexus stimulation and suppressed the induction of atrial fibrillation. Suppression of atrial fibrillation by atropine was accompanied by improved sinus and atrioventricular (AV) nodal function, increasing the ventricular heart rate observed during sinus rhythm and atrial fibrillation and eliminating the depressant actions of vagus nerve stimulation on sinoatrial (SA) and AV nodal function. Unlike atropine, mivacurium selectively antagonized the effects of vagus nerve and ganglionated plexus stimulation on atrial and pulmonary vein sleeve myocardium (shortening of action potential duration/refractoriness and increased atrial vulnerability) without altering sinus or AV nodal function under control conditions or during vagus nerve stimulation. The selective inhibition of parasympathetic nervous system effects in atrium versus sinus and AV nodes by mivacurium may represent a selective mechanism for the suppression of atrial fibrillation without altering SA and AV nodal function.

Atrial fibrillation begets atrial fibrillation: autonomic mechanism for atrial electrical remodeling induced by short-term rapid atrial pacing.

BACKGROUND: The mechanism(s) for acute changes in electrophysiological properties of the atria during rapid pacing induced atrial fibrillation (AF) is not completely understood. We sought to evaluate the contribution of the intrinsic cardiac autonomic nervous system in acute atrial electrical remodeling and AF induced by 6-hour rapid atrial pacing. METHODS AND RESULTS: Continuous rapid pacing (1200 bpm, 2x threshold [TH]) was performed at the left atrial appendage. Group 1 (n=7) underwent 6-hour pacing immediately followed by ganglionated plexi (GP) ablation; group 2 (n=7) underwent GP ablation immediately followed by 6-hour pacing; and group 3 (n=4) underwent administration of autonomic blockers, atropine (1 mg/kg), and propranolol (0.6 mg/kg) immediately followed by 6-hour pacing. The effective refractory period (ERP) and window of vulnerability (WOV, in milliseconds), ie, the difference between the longest and the shortest coupling interval of the premature stimulus that induced AF, were measured at 2xTH and 10xTH at the left atrium, right atrium, and pulmonary veins every hour before and after GP ablation or autonomic blockade. In group 1, ERP was markedly shortened in the first 2 hours and then stabilized both at 2xTH and 10xTH; however, WOV was progressively widened throughout the 6-hour period. After GP ablation, ERP was significantly longer than before ablation and AF could not be induced (WOV=0) at either 2xTH or 10xTH. In groups 2 and 3, rapid atrial pacing failed to shorten the ERP. AF could not be induced in 6 of 7 dogs in group 2 and all 4 dogs in group 3 during the 6-hour pacing period. CONCLUSIONS: The intrinsic cardiac autonomic nervous system plays a crucial role in the acute stages of atrial electrical remodeling induced by rapid atrial pacing.

Ganglionated plexi modulate extrinsic cardiac autonomic nerve input: effects on sinus rate, atrioventricular conduction, refractoriness, and inducibility of atrial fibrillation.

OBJECTIVES: This study sought to systematically investigate the interactions between the extrinsic and intrinsic cardiac autonomic nervous system (ANS) in modulating electrophysiological properties and atrial fibrillation (AF) initiation. BACKGROUND: Systematic ganglionated plexi (GP) ablation to evaluate the extrinsic and intrinsic cardiac ANS relationship has not been detailed. METHODS: The following GP were exposed in 28 dogs: anterior right GP (ARGP) near the sinoatrial node, inferior right ganglionated plexi (IRGP) at the junction of the inferior vena cava and atria, and superior left ganglionated plexi (SLGP) near the junction of left superior pulmonary vein and left pulmonary artery. With unilateral vagosympathetic trunk stimulation (0.6 to 8.0 V, 20 Hz, 0.1 ms in duration), sinus rate (SR), and ventricular rate (VR) during AF were compared before and after sequential ablation of SLGP, ARGP, and IRGP. RESULTS: The SLGP ablation significantly attenuated the SR and VR slowing responses with right or left vagosympathetic trunk stimulation. Subsequent ARGP ablation produced additional effects on SR slowing but not VR slowing. After SLGP + ARGP ablation, IRGP ablation eliminated VR slowing but did not further attenuate SR slowing with vagosympathetic trunk stimulation. Unilateral right and left vagosympathetic trunk stimulation shortened the effective refractory period and increased AF inducibility of atrium and pulmonary vein near the ARGP and SLGP, respectively. The ARGP ablation eliminated ERP shortening and AF inducibility with right vagosympathetic trunk stimulation, whereas SLGP ablation eliminated ERP shortening but not AF inducibility with left vagosympathetic trunk stimulation. CONCLUSIONS: The GP function as the "integration centers" that modulate the autonomic interactions between the extrinsic and intrinsic cardiac ANS. This interaction is substantially more intricate than previously thought.