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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 ”

View Article: PubMed Central - PubMed

ABSTRACT

Background: Botulinum 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 results: Bilateral 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.

Conclusions: Temporary 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.

No MeSH data available.


An example of the electrogram recordings from pacemakers interrogated 2 months after the first operation from a group 2 dog on the day without rapid atrial pacing. In the left panel, the atrial rate of >280 bpm is shown as a circle at 280 bpm due to the limited y‐axis scale. Sustained AF is confirmed from the stored electrograms is denoted by the dotted box.
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jah31615-fig-0003: An example of the electrogram recordings from pacemakers interrogated 2 months after the first operation from a group 2 dog on the day without rapid atrial pacing. In the left panel, the atrial rate of >280 bpm is shown as a circle at 280 bpm due to the limited y‐axis scale. Sustained AF is confirmed from the stored electrograms is denoted by the dotted box.

Mentions: The atrial capturing rates were similar between group 1 and group 2 dogs during RAP (188±12 versus 193±7 ms, P=NS). Electrogram recordings from the cardiac pacemaker were checked weekly on the day that RAP was discontinued in all dogs after the first operation. The atrial tachyarrhythmia burden increased significantly from the fifth week in group 2, compared with that of group 1 dogs (Figure 2). Three of 7 dogs in group 2 remained in sustained AF without sinus rhythm on the day without RAP (1 at 4 weeks, 1 at 7 weeks, and 1 at 11 weeks of RAP). Figure 3 shows an example of the stored electrogram interrogated from the cardiac pacemaker 2 months after the first operation in a group 2 dog. After RAP for 2 months, RAP was temporarily discontinued. Sustained AF was noted in the group 2 dog.


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 ”
An example of the electrogram recordings from pacemakers interrogated 2 months after the first operation from a group 2 dog on the day without rapid atrial pacing. In the left panel, the atrial rate of >280 bpm is shown as a circle at 280 bpm due to the limited y‐axis scale. Sustained AF is confirmed from the stored electrograms is denoted by the dotted box.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015371&req=5

jah31615-fig-0003: An example of the electrogram recordings from pacemakers interrogated 2 months after the first operation from a group 2 dog on the day without rapid atrial pacing. In the left panel, the atrial rate of >280 bpm is shown as a circle at 280 bpm due to the limited y‐axis scale. Sustained AF is confirmed from the stored electrograms is denoted by the dotted box.
Mentions: The atrial capturing rates were similar between group 1 and group 2 dogs during RAP (188±12 versus 193±7 ms, P=NS). Electrogram recordings from the cardiac pacemaker were checked weekly on the day that RAP was discontinued in all dogs after the first operation. The atrial tachyarrhythmia burden increased significantly from the fifth week in group 2, compared with that of group 1 dogs (Figure 2). Three of 7 dogs in group 2 remained in sustained AF without sinus rhythm on the day without RAP (1 at 4 weeks, 1 at 7 weeks, and 1 at 11 weeks of RAP). Figure 3 shows an example of the stored electrogram interrogated from the cardiac pacemaker 2 months after the first operation in a group 2 dog. After RAP for 2 months, RAP was temporarily discontinued. Sustained AF was noted in the group 2 dog.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Botulinum 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 results: Bilateral 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.

Conclusions: Temporary 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.

No MeSH data available.