Ganglionated Plexi Research Articles

Biophysical Models of Minipig Right Atrial Ganglionic Plexus Principal Neurons Identified from Transcriptomics Data

The Right Atrial Ganglionic Plexus (RAGP) is a component of the intrinsic cardiac nervous system. Its neurons are critical to the cardiac pacemaker response to vagal stimulation, regulating sino‐atrial node activity. We developed single‐compartment computational models of RAGP principal neurons by incorporating ion channels identified from transcriptomics data from HT‐qPCR (High Throughput quantitative Polymerase Chain Reaction) and RNA‐sequencing of 405 principal neurons in female Yucatan minipig RAGP. Out of the ~200 genes in the transcriptomics map, we identified 13 genes that encode ion channel proteins, namely: Naf (Scn1a, Nav 1.1), KDR (Kcnc1, Kv 3.1; Kcnab1, Kv 1.1), P‐, N‐, L‐, T‐type Ca2+ (Cacna1a, Cav 2.1; Cacna1b, Cav 2.2; Cacna1c, Cav 1.2; Cacna1g, Cav 3.1; Cacna1i, Cav 3.3), KA (Kcnd2) and HCN1, HCN2, HCN3, HCN4. The corresponding Hodgkin‐Huxley‐based kinetic models of these ion channel isoforms were mined from databases: Ion Channel Genealogy, Channelpedia, and ModelDB. Since each ion channel gene had several kinetic models associated with it, we ran multiple simulations on the NetPyNE software to identify a single model per gene that would best represent the channel's dynamic behaviour in the assembled electrophysiological model. A binary transcriptomic map of the 13 genes showed 101 distinct ion channel combinations. Our 505 electrophysiological models (5 sets of the 101 cells) elicited two primary firing profiles. 65% elicited a single‐spike phasic response, ~32% elicited a tonic firing in response to a current clamp stimulus, and ~3% produced tonic firing that continued after the stimulus. The firing frequencies increased by ~13 Hz for every 0.1 nA increase in the current clamp stimulus and decreased by ~11 Hz for every 0.01 S/cm2 increase in KA channel conductance. Our electrophysiological models are available to the SPARC community in NetPyNE and NIH’s O2S2PARC platform. The models exhibit phasic and tonic excitability profiles with phasic being more prevalent. We next aim to incorporate neuromodulatory inputs and simulate a network of these neuronal models.

Decreased Vessel Density in Retinal Capillary Plexus and Thinner Ganglion Cell Complex Associated With Cognitive Impairment.

BackgroundTo determine the association of the retinal capillary plexus (RCP) and ganglion cell complex (GCC) with cognitive impairment using optical coherence tomography angiography (OCTA).MethodsA cross-sectional, community-based study utilizing data from the participants enrolled between August 2019 and January 2020 in the Jidong Eye Cohort Study. We assessed the vessel density in RCP and GCC thickness using OCTA, and cognitive testing using the Montreal Cognitive Assessment (MoCA). Cognitive impairment in this study was defined as MoCA score < 24. We used multivariable analysis to evaluate the association of RCP and GCC with cognitive impairment after adjusting for confounders.ResultsThis study analyzed 1555 participants. The mean age of participants was 52.3 (8.4) years, and 861 (55.4%) were women. Cognitive impairment was observed in 268 (17.2%) participants. The adjusted odds ratio (OR) with 95% confidence interval (95% CI) for parafovea vessel density in the deep RCP with cognitive impairment was 1.20 (1.03–1.39). For vessel area and length density surrounding foveal avascular zone with cognitive impairment, the ORs with 95% CIs were 1.23 (1.07–1.41) and 1.30 (1.13–1.49), respectively. For thickness in the superior GCC with cognitive impairment, the OR with 95% CI was 1.16 (1.01–1.32).ConclusionLower vessel density in the RCP and thinner GCC were associated with cognitive impairment. Our results suggest that alterations in the RCP and GCC could provide further evidence when assessing the cognitive function and may even be potentially useful biomarkers in the detection of cognitive impairment.

Pulmonary vein isolation with adjunctive left atrial ganglionic plexus ablation for treatment of atrial fibrillation: a meta-analysis of randomized controlled trials.

Adjunctive ganglionic plexus (GP) ablation may increase the efficacy of pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF). Prior meta-analyses examining PVI with adjunctive GP ablation have included non-randomized trials and have included trials evaluating thorascopic epicardial ablation. The objective of this study is to perform a meta-analysis of randomized controlled trials (RCTs) comparing endocardial catheter-based PVI to PVI with adjunctive GP ablation. Summary odds ratio (OR) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed with I2 values. Sub-group analysis was performed comparing arrhythmia recurrence between patients with paroxysmal versus persistent AF at trial baseline. Meta-regressions were performed with mean left atrial diameter and left ventricular ejection fraction at trial baseline as the moderator variables. Five RCTs were identified including 814 patients: 406 PVI + GP ablation and 408 PVI alone. The mean age of participants was 56.5years and 74.7% were male. Four of these trials evaluated catheter-based endocardial ablation for a total of 574 patients: 289 PVI + GP ablation and 285 PVI alone. The odds of arrhythmia recurrence in patients undergoing adjunctive GP ablation with PVI compared with PVI alone were a reduced: odds ratio (OR) 0.58, 95% confidence interval (CI) 0.41-0.82, I2 = 40.2%. In the subgroup analysis, the odds of arrhythmia recurrence with adjunctive GP ablation were reduced in those with paroxysmal AF (OR 0.396, 95% CI 0.23-0.69, I2 = 0%). A non-significant trend to reduced arrhythmia recurrence was also observed in those with persistent AF (OR 0.726, 95% CI 0.475-1.112, I2 = 0%). When performing the meta-regression, increased left atrial diameter was associated with decreased treatment effect of adjunctive GP ablation (R2 index = 1.0, I2 = 0%). The addition of GP ablation to PVI was associated with reduced arrhythmia recurrence. Adjunctive GP ablation was more effective in paroxysmal AF and in patients with smaller atria. Larger RCTs are needed to confirm the efficacy of GP + PVI ablation.

CD3+ T-Lymphocytic Coeliac-Mesenteric Ganglioneuritis Associated with Colonic Torsion and Inflammatory Bowel Disease in an Arabian Broodmare

A 5-year-old Arabian broodmare with acute colic was diagnosed with lymphocytic ganglioneuritis of the coeliac-mesenteric ganglia and lymphocytic‒plasmacytic enterocolitis resembling inflammatory bowel disease. No significant pathogens were identified by aerobic culture or histopathological examination. The ganglia were multifocally infiltrated with small lymphocytes that were immunopositive for CD3 and negative for CD20 and CD79a antigens, indicating CD3+ T-lymphocyte-mediated coeliac-mesenteric ganglioneuritis. The findings suggest immune-mediated inflammatory bowel disease resulting in disturbance of the autonomic nervous system in the gastrointestinal tract, as in ulcerative colitis in humans. Histopathological features in this case differ from those of equine enteric dysautonomia and chronic intestinal pseudo-obstruction, which are characterized by neuronal degeneration and inflammation, respectively, and mostly affect the mural ganglion plexuses. To the best of our knowledge, this is the first report of CD3+ T-lymphocytic extramural enteric ganglioneuritis in equine inflammatory bowel disease.

Blocking Intermediate-Conductance Calcium-Activated Potassium Channels in the Macrophages Around Ganglionated Plexi Suppresses Atrial Fibrillation Vulnerability in Canines With Rapid Atrial Pacing.

Previous studies have indicated that ganglionated plexi (GP) function influences atrial fibrillation (AF) vulnerability, and intermediate-conductance calcium-activated potassium channels (SK4) have a close relationship with cardiomyocyte automaticity and the induction of AF. However, the effects of the SK4 inhibitor on GP function and AF vulnerability are unknown. Eighteen beagles were randomly divided into a control group (n = 6), rapid atrial pacing (RAP) group (n = 6), and triarylmethane-34 (TRAM-34, an SK4 inhibitor) group (n = 6). TRAM-34 (0.3 ml, 15 mmol/L) and saline were locally injected into GPs in the TRAM-34 group dogs and dogs from the other groups, respectively. After that, dogs in the RAP and TRAM-34 groups were subjected to RAP, and the neural activity of anterior right GP (ARGP) and atrial electrophysiology were measured. The levels of inflammatory cytokines and function of macrophages in the ARGP were measured in the three groups. At 10 min after TRAM-34 injection, ARGP activity and atrial electrophysiology did not significantly change. The atrial pacing shortened effective refractory period (ERP) values at all sites and increased the AF vulnerability and ARGP neural activity, while TRAM-34 reversed these changes. The levels of CD68 + cells, induced nitric oxide synthase (iNOS), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the ARGP tissues were higher in the RAP group and TRAM-34 group than they were in the control group. Furthermore, the levels of the CD68 + cells, iNOS, and inflammatory cytokines in the ARGP tissues were higher in the pacing group than those in the TRAM-34 group. Based on these results, administration of TRAM-34 into the atrial GP can suppress GP activity and AF vulnerability during atrial pacing. The effects of TRAM-34 might be related to macrophage polarization and the inflammatory response of GP.

Ectopy-triggering ganglionated plexuses ablation to prevent atrial fibrillation: GANGLIA-AF study.

BackgroundThe ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system may play a role in atrial fibrillation (AF).ObjectiveWe hypothesized that ablating the ectopy-triggering GPs (ET-GPs) prevents AF.MethodsGANGLIA-AF (ClinicalTrials.gov identifier NCT02487654) was a prospective, randomized, controlled, 3-center trial. ET-GPs were mapped using high frequency stimulation, delivered within the atrial refractory period and ablated until nonfunctional. If triggered AF became incessant, atrioventricular dissociating GPs were ablated. We compared GP ablation (GPA) without pulmonary vein isolation (PVI) against PVI in patients with paroxysmal AF. Follow-up was for 12 months including 3-monthly 48-hour Holter monitors. The primary end point was documented ≥30 seconds of atrial arrhythmia after a 3-month blanking period.ResultsA total of 102 randomized patients were analyzed on a per-protocol basis after GPA (n = 52; 51%) or PVI (n = 50; 49%). Patients who underwent GPA had 89 ± 26 high frequency stimulation sites tested, identifying a median of 18.5% (interquartile range 16%–21%) of GPs. The radiofrequency ablation time was 22.9 ± 9.8 minutes in GPA and 38 ± 14.4 minutes in PVI (P < .0001). The freedom from ≥30 seconds of atrial arrhythmia at 12-month follow-up was 50% (26 of 52) with GPA vs 64% (32 of 50) with PVI (log-rank, P = .09). ET-GPA without atrioventricular dissociating GPA achieved 58% (22 of 38) freedom from the primary end point. There was a significantly higher reduction in antiarrhythmic drug usage postablation after GPA than after PVI (55.5% vs 36%; P = .05). Patients were referred for redo ablation procedures in 31% (16 of 52) after GPA and 24% (12 of 50) after PVI (P = .53).ConclusionGPA did not prevent atrial arrhythmias more than PVI. However, less radiofrequency ablation was delivered to achieve a higher reduction in antiarrhythmic drug usage with GPA than with PVI.

Microscopic structure of the ganglia of the solar plexus and other ganglia of the marginal trunk of the sympathetic nerve

In my work on the fine structure of the intracardiac nervous system of mammals (Proceedings of the Society of Russian Doctors in St. Petersburg for 1907), I proposed a new classification of sympathetic ganglion cells, based on the principle that a given cell belonged to one type or another, depending on whether what type of terminal apparatuses end its dendrites. In this work, I have described in more or less detail four of these main types of ganglion cells, and a large number of drawings taken from the corresponding preparations are attached to the German text of this work (Internat. Monatsschrift fr Anatomie und Physiologie. Bd. XXV. 1908).

Role and mechanism of lncRNA under magnetic nanoparticles in atrial autonomic nerve remodeling during radiofrequency ablation of recurrent atrial fibrillation

ABSTRACT It aimed to investigate the mechanism of magnetic nanoparticles (MNPs) on atrial fibrillation and effect of n-isopropyl acrylamide coated MNPs (NIPA-co-MN) on the treatment of atrial fibrillation. Ten beagles weighing 20 − 25 kg were randomly divided into test group and control group. Dogs with atrial fibrillation were set as test group, and non-atrial fibrillation dogs as control group. The expression of long non-coding RNA (lncRNA) differentially expressed in the right anterior adipose pad in atrial fibrillation and non-atrial fibrillation dogs was detected by high-throughput sequencing. The relationship between lncRNA and cardiac autonomic nerve remodeling (CANR) was explored. In addition, 20 beagles weighing 20–25 kg were selected to study the therapeutic effect of n-isopropylacrylamide magnetic nanoparticles (NIPA-co-MN) on atrial fibrillation, and statistical analysis was performed. The volume and number of new neurons in the anterior right fat pad of atrium of test group were larger than the control group. The test group dogs produced 45 brand-new lncRNA, including 15 up-regulated transcripts and 30 down-regulated transcripts. MNPs injection can slow down the reduction of ventricular rate in right inferior ganglion plexus. The anterior right ganglion plexus resulted in a reduced amplitude of sinus tachyarrhythmia. This study provided references for the discovery of new diagnostic biomarkers or therapeutic targets and for the treatment of patients with atrial fibrillation.

Importance of vagal tone before atrial fibrillation onset

Neuromodulation is increasingly attempted during ablation procedures for atrial fibrillation (AF). The role of the cardiac autonomic nervous system (CANS) in triggering paroxysmal AF episodes is well-established. Heart rate variability (HRV) provides information on the final output of the influence of the CANS. The high frequency component (HF: 0.15–0.40 Hz) reflects vagal activity, and the low frequency component (LF: 0.04–0.15 Hz) reflects a complex mix of parasympathetic, sympathetic, and other unidentified non-linear factors. Therefore, clinically, the analysis of the temporality of these parameters could be useful for the selection of additional therapy during AF ablation procedures. Study the significance of CANS variations prior to AF onset by tracking the evolution of frequential parameters of HRV and premature atrial contractions (PACs). We screened our ECG Holter monitoring database of more than 20,000 patients to find those with paroxysmal AF episodes recorded. Three hundred analyzable AF onsets from 210 paroxysmal AF patients were labelled. We analyzed HRV frequential parameters by segments every 300 RR intervals, progressing beat by beat to allow the evolution of the spectral parameters of the HRV and count of PACs to be closely monitored. We focused on the evolution of low (LF) and high frequencies (HF), as well as the LF/HF ratio and the number of PACs. We observed several cyclical variations of increasing amplitude in CANS followed by a final significant upward shift in HF and LF preceding the onset of AF. The number of PACs shows a progressive increase in parallel to autonomic changes (see Fig. 1 ). These data suggest that vagal influence is preponderant in the AF onset for most of the patients. This is in favor of a thoracoscopic approach to neuromodulation procedures, as ganglionic plexi contain mainly parasympathetic neurons and are located in epicardial fat pads.

High-power and short-duration ablation with the Qdot+ algorithm for pulmonary vein isolation and the right superior ganglion plexus ablation without fluoroscopy

In this report we present pulmonary vein and posterior box isolation together with the right superior ganglion plexus ablation using the Qdot Micro catheter without fluoroscopy. We describe different possibilities of this new technology for catheter ablation. The main advantages of this catheter to potentially increase ablation safety and effectiveness are discussed. Specifically, the possibility to perform high-density mapping with the lowest available distance between points. Furthermore, the possibility to decrease the risk of collateral tissue damage and to improve atrial linear lesions contiguity, transmurality and durability due to the dominance of resistive heating supported by the feedback temperature control. Finally, the possibility to shorten the procedure and fluoroscopy duration due to the high shortening of application duration to 4 seconds only.

Catheter ablation of ganglionated plexi in patients with adenosine triphosphate-induced atrial fibrillation after pulmonary vein isolation.

Intravenous ATP may induce atrial fibrillation (AF). ATP shares similar receptor-effector coupling systems with acetylcholine. However, the association between an ATP injection and the hyperactivity of the intrinsic cardiac autonomic nervous system, known as ganglionated plexi (GPs), is not well understood. We describe a series of patients with non-pulmonary vein (PV) trigger sites provoked by an ATP injection, and assess the feasibility of a ganglionated plexus (GP) ablation. We retrospectively analyzed 547 patients (69% male; mean age 67.4 ± 10.4years; 38.5% non-paroxysmal AF) who underwent a total of 604 ablation procedures. Intravenous ATP was administered with an isoproterenol infusion during sinus rhythm after a pulmonary vein isolation in 21.3%, Box isolation in 78.6%, and SVC isolation in 52.0% of the procedures, respectively. We reviewed the incidence, the distribution of the foci, and the ablation outcomes in patients with ATP-induced AF. A total of seven patients (1.3%) had ATP-induced AF. Foci were identified in the coronary sinus (CS) in six patients, right atrial posterior wall (RAPW) adjacent to the interatrial groove in two, mitral annulus in two, ligament of Marshall in one, right septum below the foramen ovale in one and left atrial posterior wall in one, respectively. Among these trigger foci, we confirmed the vagal response by high-frequency stimulation in the CS and RAPW in six and two patients, respectively. After a median RF time of 2.9min (range 2.5-11.3) targeting these foci, in five of six patients who received a repeat ATP injection, the AF became non-inducible. ATP-provoked trigger foci were distributed among certain sites that overlapped with the distribution of the GPs. The GP ablation was effective for this rare, but challenging situation.

Pathohistological study of the ganglion plexuses of the sigmoid colon in patients with chronic slow-transit constipation

The morphological study of the resected sections of the colon obtained at the S.P. Fedorov Department of Faculty Surgery of S.M. Kirov Military Medical Academy, as a result of surgical treatment of patients with severe chronic slow-transit constipation, included an assessment of the changes in the structures of ganglion plexuses. Three cases were considered (women, aged 3740 years). Various degrees of pathological changes were detected in the ganglion plexuses (Auerbach and Meissner) of the sigmoid colon from patients with chronic slow-transit constipation using Nissls toluidine blue staining. In all cases, reactive, dystrophic, severe degenerative-necrotic changes of ganglion cells, as well as the details of their death, were described in detail. Along with pathological changes in nerve cells in the myenteric nerve plexus and gliosis, features of neuronglial relationships were described, and the death of ganglion cells in the human colon with the active participation of specialized astrocyte-like glial cells was also established for the first time. In the third case, a pattern of pronounced dysplasia and dysgangliogenesis was revealed in the myenteric ganglion plexus of the sigmoid colon, and the presence of diffuse lymphmonocytic infiltrates was noted in the circular muscle layer. Pathological changes in the enteral nervous system in chronic slow-transit constipation reflect neuropathy, which can serve as the main cause of impaired intestinal functions and of some symptoms.

Vagal response during circumferential pulmonary vein isolation decreases the recurrence of atrial fibrillation in the short-term in patients with paroxysmal atrial fibrillation: A prospective, observational study

BackgroundVagal responses (VRs) are often seen in patients undergoing circumferential pulmonary vein isolation (CPVI). The possible mechanism of VR is that CPVI creates a coincidental modification of the cardiac ganglionated plexi (GP). AimTo investigate whether the presence of VR during CPVI impacts post-ablation recurrence in patients with paroxysmal atrial fibrillation (AF). MethodsA total of 112 consecutive patients with symptomatic paroxysmal AF who underwent CPVI for the first time from October 1, 2017 to April 30, 2019 were prospectively enrolled, of which two were lost the follow-up. Patients were divided into two groups based on whether VRs were experienced during CPVI. Electrophysiological parameters, including atrial effective refractory period (AERP) and mean heart rate (MHR), were measured before and post-ablation. The patients were then followed up for 12 months. ResultsThe 71 patients who had experienced VRs during CPVI were assigned to group B, and the remaing 39 patients who did not experience VR during CPVI were assigned to group A. The MHR (79.6 ± 8.3 vs 70.4 ± 7.8 b/min; p ≤ 0.001) was significantly higher; and the AERP (244 ± 22 vs 215 ± 27 ms; p ≤ 0.001) was prolonged in group B compared to respective pre-ablation values. There were no significant changes in the MHR (69.5 ± 7.9 vs 69.7 ± 8.7 b/min; p = 0.541) and AERP (224 ± 28 vs 225 ± 33 ms; p = 0.542) in group A. During the first four months of follow-up after ablation, the MHR gradually slowed down to pre-procedural levels in group B. The recurrence of AF (6/71 vs 7/39; p = 0.023) significantly decreased in group B relative to group A during the first 6 months after ablation, but there was no significant difference (14/71 vs 9/39; p = 0.598) at the end of the 12-month follow-up period. ConclusionPatients with paroxysmal AF who develop VRs during CPVI might have a decreased recurrence of AF and accelerated MHR in the short-term.

Temporary prolongation of corrected QT interval after cardioneuroablation for functional bradyarrhythmias

Abstract Background There are controversial reports on QT interval response to ganglionic plexi ablation that are selectively targeted during cardioneuroablation (CNA) or occurs as collateral lesion during left atrial ablation procedures. Both shortening or prolongation of the heart-rate corrected QT interval (QTc) with therapeutic or safety implications were described. Purpose In this retrospective study, we investigated longitudinal changes of QTc after CNA. Methods The study included 108 patients (age: 39±12 years, 60% males) who underwent biatrial cardioneuroablation (radiofrequency time: 15.5±6.7 min) for symptomatic functional bradyarrhythmias. Surface ECG examinations were performed on the day before the CNA (N=108), 1 hour after the CNA (N=106), on the 1st post-ablation day (N=50), at the 3-month (N=99), and 1-year (N=63) follow-up visits. Automated measurements of QT interval were employed for the analysis. Four formulas (Bazett, Framingham, Fridericia, and Hodges) were used for the correction of QT interval to instant heart rate. Results QTc significantly prolonged immediately after the CNA with rapid return to baseline values (Figure and Table). This was particularly valid for QT correction by Framingham formula (and similarly for Fridericia and Hodges formulas). The QTc by Bazett formula, which is known to overestimate QT at higher heart rates, returned to baseline more slowly and incompletely. Several mechanisms may contribute to observed QTc dynamics: (1) direct effect of autonomic denervation with recovery phenomenon; (2) QT hysteresis with an extremely long time constant; or (3) artifact due to suboptimum QT correction to a substantial change of heart rate. Conclusions The study suggests that CNA produces acute prolongation of QTc interval with rapid decay and virtual normalization in 3 months. CNA in otherwise healthy subjects is not likely associated with substantial long-term risk of long-QT-associated arrhythmias. In the same way, we cannot confirm earlier observations of clinically significant QTc shortening effect of ganglionated plexi ablation. Funding Acknowledgement Type of funding sources: None. Figure 1Table 1

An off-pump biatrial mini-maze procedure for treatment of long-standing persistent atrial fibrillation

Abstract Background Surgical treatment has assumed a more prominent role in the therapy of atrial fibrillation (AF) with favorable efficiency and acceptable safety during the last decades. The traditional Cox-Maze procedure and Wolf Mini-Maze procedure focused on left atrial ablation. However, it is ubiquitous that patients with long-standing persistent atrial fibrillation (LSPAF) typically suffer from biatrial electrical and structural remodeling. The left atrial procedures are still not enough in patients with LSPAF. Purpose Herein, we aimed to introduce a modified biatrial off-pump ablation procedure based on the Wolf Mini-Maze procedure and to detect the safety and efficacy of the surgery for patients with LSPAF. Methods Between January 2016 and September 2020, 102 patients of LSPAF underwent our modified Mini-Maze procedure using bipolar radiofrequency ablation. Those patients firstly underwent a Mini-Maze procedure using Dallas lesion set, including video-assisted bilateral mini-thoracotomy, left atrial appendage excision, bilateral pulmonary vein isolation, ganglionic plexi evaluation and destruction, left atrial roof connecting lesion, and a linear lesion connecting this roofline to the root of the aorta at the junction of the left coronary and the non-coronary cusp. Secondly, a purse-string suture was performed on the right atrium, and then four ablation lesions were made to the superior vena cava, to the inferior vena cava, to the appendix of the right atrium, and to the tricuspid valve annulus from the purse-string suture point by the bipolar radiofrequency clamp. After the operation, the patients were followed up at an interval of 3, 6, 12 months, and every 1 year after that. Results No mortality No surgical re-exploration for bleeding. No permanent pacemaker implantation. 99 patients were free from LSPAF upon discharge. A follow-up at interval of 3, 6, 12, 24, 36, and 48 months showed a success rate free from LSPAF was 95.1% (97/102), 94.4% (85/90), 94.8% (73/77), 91.5% (54/59), 90.3% (28/31) and 100% (9/9), respectively Conclusions The modified biatrial Mini-Maze suggested a safe and feasible procedure. Early follow-up demonstrated an acceptable success rate free from AF. It might have the potential to become another option for clinical treatment of LSPAF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): General Program of the National Natural Science Foundation of China Schematic of the procedure

Acute change in parasympathetic cardiac innervation after pulmonary vein isolation by pulse-field and radiofrequency energy

Abstract Background In patients with atrial fibrillation (AF), pulmonary vein isolation (PVI) by radiofrequency (RF) energy is associated with a significant change of cardiac autonomic regulations due to collateral ganglionic plexi ablation. Pulse-field (PF) ablation energy presumably spares neural tissue. Purpose We compared the effect of PVI by PF and RF energy on cardiac autonomic function. Methods A study enrolled 23 patients who underwent PVI in general anaesthesia. In 12 patients, a novel lattice-tip catheter and PF energy were used for ablation while 11 patients were ablated using a conventional irrigated-tip catheter and RF energy. The response of the sinus node (SAN) and atrioventricular node (AVN) to extracardiac high-frequency vagal stimulation (ECVS) was tested before and after PVI (via right internal jugular vein; stimulation frequency of 50 Hz; pulse width of 0.05 ms; output of 1 V/kg (&amp;lt;70V); train duration of 5 s). Results At baseline, physiological massive response to ECVS (sinus arrest and/or AV block) was demonstrated in the majority of patients. After PVI, complete loss of autonomic response of the SAN in 11/11 (100%) and 3/12 (25%) patients (p=0.003), and the AVN in 9/11 (82%) and 3/12 (25%) patients (p=0.01) was observed in RF and PF groups, respectively. The figure shows the maximum duration of the pause in sinus rhythm (maximum P-P interval) and AVN block (maximum R-R interval during atrial pacing) induced by ECVS after PVI. Conclusion Cardiac vagal response is preserved in a considerable proportion of AF patients after PF ablation which is in contrast with a significantly stronger effect of RF energy. This may influence the clinical outcome of AF ablation procedures. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Institute for Clinical and Experimental Medicine, Prague

Anti-arrhythmic and anti-heart failure effects of low-level electrical stimulation on aortic root ventricular ganglionated plexi.

It remains uncertain whether low-level electrical stimulation (LL-ES) of the ventricular ganglionated plexi (GP) improves heart function. This study investigated the anti-arrhythmic and anti-heart failure effects of LL-ES of the aortic root ventricular GP (ARVGP). Thirty dogs were divided randomly into control, drug, and LL-ES groups after performing rapid right ventricular pacing to establish a heart failure (HF) model. The inducing rate of arrhythmia; levels of bioactive factors influencing HF, including angiotensin II type I receptor (AT-1R), transforming growth factor-beta (TGF-β), matrix metalloproteinase (MMP), and phosphorylated extracellular signal-regulated kinase (p-ERK1/2); left ventricular stroke volume (LVSV), and left ventricular ejection fraction (LVEF)were measured after treatment with placebo, drugs, and LL-ES. The inducing rate of atrial arrhythmia decreased from 60% in the control group to 50% in the drug group and 10% in the LL-ES group (p=.033vs. drug group) after 1week of treatment. The ventricular effective refractory period was prolonged from 139 ± 8ms in the drug group to 166 ± 13ms in the LL-ES group (p=.001). Compared to the drug group, the expressions of AT-1R, TGF-β, and MMP proteins were down-regulated in the LL-ES group, whereas that of p-ERK1/2 was significantly increased (all p=.001). Moreover, in the LL-ES group, LVSV increased markedly from 13.16 ± 0.22 to 16.86 ± 0.27mL, relative to that in the drug group (p=.001), and LVEF increased significantly from 38.48% ± 0.53% to 48.94% ± 0.57% during the same time frame (p=.001). Short-term LL-ES of ARVGP had both anti-arrhythmic and anti-inflammatory effects and contributed to the treatment of tachycardia-induced HF and its associated arrhythmia.

Electrical properties and synaptic transmission in mouse intracardiac ganglion neurons in situ.

The intrinsic cardiac nervous system represents the final site of signal integration for neurotransmission to the myocardium to enable local control of cardiac performance. The electrophysiological characteristics and ganglionic transmission of adult mouse intrinsic cardiac ganglion (ICG) neurons were investigated using a whole‐mount ganglion preparation of the excised right atrial ganglion plexus and intracellular microelectrode recording techniques. The passive and active electrical properties of ICG neurons and synaptic transmission including synaptic response strength and efficacy as a function of stimulation frequency were examined. The resting membrane potential and input resistance of ICG neurons were −47.9 ± 4.0 mV and 197.2 ± 81.5 MΩ, respectively. All neurons had somatic action potentials with overshoots of >+15 mV and after‐hyperpolarizations having an average of 10 mV amplitude and ~45 ms half duration. Phasic discharge activities were recorded from the majority of neurons studied and several types of excitatory synaptic responses were recorded following inputs from the vagus or interganglionic nerve trunk(s). Most postganglionic neurons (>75%) received a strong, suprathreshold synaptic input and reliably followed high‐frequency repetitive nerve stimulation up to at least 50 Hz. Nerve‐evoked synaptic transmission was blocked by extracellular Cd2+, ω‐conotoxin CVIE, or α‐conotoxin RegIIA, a selective α3‐containing nicotinic acetylcholine receptor antagonist. Synaptic transmission and the electrical properties of murine ICG neurons contribute to the pattern of discharge which regulates chronotropic, dromotropic, and inotropic elements of cardiac function.

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.

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.