Identification and Characterization of Atrioventricular Parasympathetic Innervation in Humans

Quan, Kara J.; Lee, Jai H.; Hare, George F. Van; Biblo, Lee A.; Mackall, Judith A.; Carlson, Mark D.

doi:10.1046/j.1540-8167.2002.00735.x

Cited by 106 publications

(57 citation statements)

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“…38 The AV-node is highly innervated by parasympathetic nerve fibers where Na v 1.8 is expressed. [39][40][41] Recognition of disease mechanisms overlap between the AF and AV-nodal re-entry tachycardia, and the fact that AVNRT may be the triggering factor for AF has been reported in several studies. [42][43][44][45] Consistent with this notion, several of our paroxysmal AF patients with the rare variants have AVNRT (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…46 Changes in autonomic tone, also known as sympathovagal imbalance, are important triggers in some forms of paroxysmal AF and also in the generation and maintenance of persistent AF. [41][42][43] With the expression of Na v 1.8 channels in vagal fibers and their absence in sympathetic fibers, it is possible that the observed effects on Na v 1.8 function of the different variants alters the sympathovagal balance. 19,20,22 We were able to examine 3 families for cosegregation of SCN10A variants identified in the respective probands (Table 1), but none of the family members diagnosed with AF carried the variant of the proband.…”

Section: Discussionmentioning

confidence: 99%

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Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Jabbari

Olesen

Yuan

et al. 2015

Circ Cardiovasc Genet

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2=0.933). We therefore sought to determine whether common and rare SCN10A variants are associated with early onset AF. Methods and Results-SCN10A was sequenced in 225 AF patients in whom there was no evidence of other cardiovascular disease or dysfunction (lone AF). In an association study of the rs6795970 single nucleotide polymorphism variant, we included 515 AF patients and 2 control cohorts of 730 individuals free of AF and 6161 randomly sampled individuals. Functional characterization of SCN10A variants was performed by whole-cell patch-clamping. In the lone AF cohort, 9 rare missense variants and 1 splice site donor variant were detected. Interestingly, AF patients were found to have higher G allele frequency of rs6795970, which encodes the alanine variant at position 1073 (described from here on as A1073, odds ratio =1 ). Both of the common variants, A1073 and P1092, induced a gain-of-channel function, whereas the rare missense variants, V94G and R1588Q, resulted in a loss-of-channel function. Conclusions-The common variant A1073 is associated with increased susceptibility to AF. Both rare and common variants have effect on the function of the channel, indicating that these variants influence susceptibility to AF. Hence, our study suggests that SCN10A variations are involved in the genesis of AF. (Circ Cardiovasc Genet. 2015;8:64-73.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Jabbari

Olesen

Yuan

et al. 2015

Circ Cardiovasc Genet

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“…21 Numerous studies have observed multiple major and small GPs in the atria of mammalian hearts. 19,[22][23][24] These GPs modulate the interaction and balance between the extrinsic and intrinsic autonomic nervous system and contain efferent cholinergic and adrenergic neurons which influence the atrial myocardium, 25 in terms of action potential duration, AERP, and conduction velocity. In many animal studies, autonomic denervation exhibited short-term efficacy.…”

Section: Changes In the Electrophysiological Characteristics In The Tmentioning

confidence: 99%

Long-Term Effects of Ganglionated Plexi Ablation on Electrophysiological Characteristics and Neuron Remodeling in Target Atrial Tissues in a Canine Model

Wang

Zou

Zhang

et al. 2015

Circ: Arrhythmia and Electrophysiology

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Background-The long-term effects of ganglionated plexi ablation on electrophysiological characteristics and neuron remodeling in target atrial tissues remain unclear. Methods and Results-Dogs in group 1 (control, n=8) were not subjected to ganglionated plexi ablation and observed for 1 month, and dogs in groups 2 to 4 (ablation groups, n=8 each) underwent ablation of the right-sided ganglionated plexi and observed for 1, 6, and 12 months, respectively. Atrial electrophysiological characteristics were examined before ablation, immediately and continuously after ablation. Target atrial tissues were subjected to immunohistochemical staining and Western blot analysis. Atrial effective refractory period was significantly prolonged immediately after ablation (P<0.001), and persisted for 1 month (P<0.05). Nerve densities decreased 1 month after ablation (P<0.001). These parameters reverted to preablation levels after 6 and 12 months. In the ablation groups, atrial fibrillation was induced in 5 of 8 dogs after 1 month and in all animals after 6 and 12 months. Atrial fibrillation was not observed in the control group and in the experimental groups immediately after ablation. Moreover, the expression of the growth-associated protein 43 was upregulated after ablation. Conclusions-Ganglionated plexi ablation effectively prolonged atrial effective refractory period for a short period, but the long-term effects on atrial effective refractory period and the suppression of atrial fibrillation induction were not persistent. Targeted atrial neuron remodeling may be an important mechanism underlying the observed electrophysiological changes.

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“…It contains abundant parasympathetic fibers that affect AV node conduction. 6,7 After proof of concept in humans, we and others developed a technique for chronic endocardial 8,9 and epicardial 10 neurostimulation of the RIGP for ventricular rate control during atrial fibrillation (AF) in dogs. Of note, the negative dromotropic effect during endocardial HFES could be maintained throughout the entire neurostimulation period of 2 years.…”

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confidence: 99%

Chronic Electrical Neuronal Stimulation Increases Cardiac Parasympathetic Tone by Eliciting Neurotrophic Effects

Rana

Saygili

Gemein

et al. 2011

Circulation Research

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Rationale: Recently, we provided a technique of chronic high-frequency electric stimulation (HFES) of the right inferior ganglionated plexus for ventricular rate control during atrial fibrillation in dogs and humans. In these experiments, we observed a decrease of the intrinsic ventricular rate during the first 4 to 5 months when HFES was intermittently shut off.Objective: We thus hypothesized that HFES might elicit trophic effects on cardiac neurons, which in turn increase baseline parasympathetic tone of the atrioventricular node. Methods and Results:In mongrel dogs atrial fibrillation was induced by rapid atrial pacing. Endocardial HFES of the right inferior ganglionated plexus, which contains abundant fibers to the atrioventricular node, was performed for 2 years. Sham-operated nonstimulated dogs served as control. In chronic neurostimulated dogs, we found an increased neuronal cell size accompanied by an increase of choline acetyltransferase and unchanged tyrosine hydroxylase protein expression as compared with unstimulated dogs. Moreover, ␤-nerve growth factor (NGF) and neurotrophin (NT)-3 were upregulated in chronically neurostimulated dogs. In vitro, HFES of cultured neurons of interatrial ganglionated plexus from adult rats increased neuronal growth accompanied by upregulation of NGF, NT-3, glial-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) expression. NGF was identified as the main growth-inducing factor, whereas NT-3 did not affect HFES-induced growth. However, NT-3 could be identified as an important acetylcholine-upregulating factor. Key Words: atrial fibrillation Ⅲ tachyarrhythmias Ⅲ acetylcholine Ⅲ nervous system D uring the last 10 years, techniques have been developed to directly and selectively interfere with the intrinsic cardiac neural system via electric stimulation catheters or leads in animals and patients. [1][2][3][4][5] The baseline observation for these applications was that depolarization of intracardiac neural fibers by high-frequency electric stimulation (HFES) delivers neurotransmitters that subsequently act locally on cardiac structures (eg, stimulation of sympathetic fibers along the coronary sinus selectively increases left ventricle inotropy). 5 Furthermore, acute, short-term endocardial HFES of the right inferior ganglionated plexus (RIGP) elicits selective negative dromotropic effects in awake patients and slows atrioventricular (AV) conduction during atrial fibrillation. 3 The RIGP is located between the inferior caval vein, the left atrium and the ostium of the coronary sinus. It contains abundant parasympathetic fibers that affect AV node conduction. 6,7 After proof of concept in humans, we and others developed a technique for chronic endocardial 8,9 and epicardial 10 neurostimulation of the RIGP for ventricular rate control during atrial fibrillation (AF) in dogs. Of note, the negative dromotropic effect during endocardial HFES could be maintained throughout the entire neurostimulation period of 2 year...

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Identification and Characterization of Atrioventricular Parasympathetic Innervation in Humans

Abstract: For the first time in humans, an epicardial fat pad was identified from which parasympathetic nerve fibers selectively innervate the AV node but not the sinoatrial node. Nerves in this fat pad also innervate the surrounding right atrium.

Cited by 106 publications

References 1 publication

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Long-Term Effects of Ganglionated Plexi Ablation on Electrophysiological Characteristics and Neuron Remodeling in Target Atrial Tissues in a Canine Model

Chronic Electrical Neuronal Stimulation Increases Cardiac Parasympathetic Tone by Eliciting Neurotrophic Effects

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