Nonuniform Distribution of Vagal Effects on the Atrial Refractory Period

Alessi, Rudá; Nusynowitz, Martin L.; Abildskov, J.A.; Moe, Gordon K.

doi:10.1152/ajplegacy.1958.194.2.406

Cited by 285 publications

(101 citation statements)

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“…Normal atria exhibit a heterogeneous distribution of vagal and sympathetic innervation. 18,21,27 An increased dispersion of atrial refractoriness has been observed in animal models of AF 2,6,7,28 and humans with paroxysmal AF. 9 Increased regional dispersion of AFCL appears to be an important independent determinant of electrophysiological remodeling and is observed even after shortening of atrial refractoriness caused by rapid pacing has stabilized.…”

Section: Role Of Sympathetic Innervation In Electrical Remodeling and Afmentioning

confidence: 99%

“…9 Increased regional dispersion of AFCL appears to be an important independent determinant of electrophysiological remodeling and is observed even after shortening of atrial refractoriness caused by rapid pacing has stabilized. 6 Whereas vagal stimulation results in regional differences in shortening of refractoriness, promoting both induction and sustenance of AF, 21,23,27 sympathetic stimulation appears to have a less pronounced effect on the dispersion of atrial refractoriness, at least in autonomically decentralized animals. 21,22 It is also of note that these studies were performed in normal animals in sinus rhythm.…”

Section: Role Of Sympathetic Innervation In Electrical Remodeling and Afmentioning

confidence: 99%

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Atrial Fibrillation Produced by Prolonged Rapid Atrial Pacing Is Associated With Heterogeneous Changes in Atrial Sympathetic Innervation

et al. 2000

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Background-Structural and electrophysiological changes of the atria occur with prolonged rapid rates; however, the effects of sustained atrial fibrillation (AF) on autonomic innervation of the atria are unknown. We hypothesized that electrophysiological remodeling from rapid atrial rates is accompanied by altered atrial autonomic innervation. Methods and Results-Six dogs (paced group) underwent atrial pacing at 600 bpm; 9 dogs (control animals) were not paced. All paced dogs developed sustained AF by week 4 of pacing. All 15 animals underwent positron emission tomography imaging of the atria with [C-11] hydroxyephedrine (HED) to label sympathetic nerve terminals. HED retention in the atria was significantly greater in paced dogs compared with control animals (Pϭ0.03). Tissue samples from the atrial appendages had a greater concentration of norepinephrine in paced animals than in control animals (Pϭ0.01). The coefficient of variation of HED retention was also greater in paced animals (Pϭ0.05) and was greater in the right atrium than in the left atrium (Pϭ0.004). Epicardial activation maps of AF were obtained in the paced animals at baseline and with autonomic manipulation. Mean AF cycle length was longer in the right atrium (109.2Ϯ5 ms) than in the left atrium (85.8Ϯ5.5 ms) at baseline (Pϭ0.005). AF cycle length did not vary significantly from baseline (97.6Ϯ13.4 ms) with stellate stimulation (100.5Ϯ6 ms) but lengthened with propranolol (107.5Ϯ6.1 ms, Pϭ0.03). Conclusions-Rapid rates of AF produce a heterogeneous increase in atrial sympathetic innervation. These changes parallel disparate effects of rapid pacing-induced AF on atrial electrophysiology.

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Section: Role Of Sympathetic Innervation In Electrical Remodeling and Afmentioning

confidence: 99%

Section: Role Of Sympathetic Innervation In Electrical Remodeling and Afmentioning

confidence: 99%

Atrial Fibrillation Produced by Prolonged Rapid Atrial Pacing Is Associated With Heterogeneous Changes in Atrial Sympathetic Innervation

et al. 2000

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“…[33][34][35] Spatially disparate effects of vagal stimulation have been demonstrated in the atria. 19,20,36 Although this heterogeneous distribution of vagal effects on electrophysiological properties may contribute to the milieu necessary to maintain multiple-wavelet atrial reentry, it is clearly not sufficient in the baseline state, because spontaneous AF does not occur in the absence of other perturbations (such as vagal stimulation).…”

Section: Role Of Autonomic Nervous System In Afmentioning

confidence: 99%

Heterogeneous Atrial Denervation Creates Substrate for Sustained Atrial Fibrillation

et al. 1998

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Background-Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atrial fibrillation (AF). We hypothesized that heterogeneous sympathetic denervation with phenol would create a milieu for sustained AF. Methods and Results-After the determination of baseline inducibility, 15 dogs underwent atrial epicardial phenol application and 11 underwent a sham procedure. After 2 weeks of recovery, the animals had repeat attempts at inducing AF and effective refractory period (ERP) testing. Epicardial maps were obtained to determine local AF cycle lengths. ERPs were determined at baseline and during sympathetic, vagal, and simultaneous vagal/sympathetic stimulation.

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“…In addition, autonomic remodeling plays an important role in the pathogenesis of AF. Several publications demonstrated that hyperactivity or imbalance of the cardiac autonomic nervous system (ANS) facilitates the initiation and maintenance of AF 4, 5, 6, 7, 8, 9, 10, 11. Hyperactivity of the cardiac ANS and AF also form a vicious cycle in which the former can initiate AF and the latter further enhance the activity of the cardiac ANS to perpetuate AF 7, 9…”

Section: Introductionmentioning

confidence: 99%

Temporary Suppression of Cardiac Ganglionated Plexi Leads to Long‐Term Suppression of Atrial Fibrillation: Evidence of Early Autonomic Intervention to Break the Vicious Cycle of “AF Begets AF”

Chang

Scherlag

et al. 2016

JAHA

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BackgroundBotulinum toxin (BTX), temporarily suppressing cholinergic transmission (<3 weeks), has been reported to suppress atrial fibrillation (AF) for ≥1 year. We aimed to investigate the mechanism underlying long‐term suppression of AF caused by injecting BTX into major atrial ganglionated plexi (GPs).Methods and ResultsBilateral thoracotomies in anesthetized dogs allowed programmed stimulation at 4 pulmonary veins, biatrial appendages, and the superior vena cava to determine the effective refractory period (ERP) in the first operation. Group 1 (n=10) received BTX injection into all GPs; group 2 (n=7) received no injection. Groups 1 and 2 received rapid atrial pacing (800 bpm) 6 days a week. Group 3 (n=7) did not undergo thoracotomy or rapid atrial pacing to serve as controls for histological studies. A second operation and the same measurements were made 3 months later. During the first operation in group 1, ERPs of 4 pulmonary veins, but not biatrial appendages or superior vena cava, increased immediately after BTX injection. AF burdens increased significantly from the fifth week after the first operation in group 2 but not in group 1. In the second operation, ERPs remained unchanged compared with ERPs before BTX injection in group 1, whereas ERPs shortened significantly at all sites except the superior vena cava in group 2. There was no difference of autonomic nerve density between group 1 and group 3. The GP choline acetyltransferase (+) and atrial tyrosine hydroxylase (+) nerve densities were higher in group 2 than in group 1 and group 3.ConclusionsTemporary suppression of major atrial GPs by BTX prevents autonomic remodeling and provides long‐term suppression of AF, indicating the critical role of GPs in AF progression.

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Nonuniform Distribution of Vagal Effects on the Atrial Refractory Period

Cited by 285 publications

References 0 publications

Atrial Fibrillation Produced by Prolonged Rapid Atrial Pacing Is Associated With Heterogeneous Changes in Atrial Sympathetic Innervation

Atrial Fibrillation Produced by Prolonged Rapid Atrial Pacing Is Associated With Heterogeneous Changes in Atrial Sympathetic Innervation

Heterogeneous Atrial Denervation Creates Substrate for Sustained Atrial Fibrillation

Temporary Suppression of Cardiac Ganglionated Plexi Leads to Long‐Term Suppression of Atrial Fibrillation: Evidence of Early Autonomic Intervention to Break the Vicious Cycle of “AF Begets AF”

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