Limits...
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.


Related in: MedlinePlus

Examples of immunohistochemical (group 1: A and C, group 2: B and D) and trichrome staining (group 1: E, group 2: F) in cardiac ganglia and myocardia. A and B, Choline acetyltransferase (ChAT) staining showing increased cholinergic neural density within ganglia in group 2 (B) than in group 1 (A). C and D, Tyrosine hydroxylase (TH) staining showing increased sympathetic innervation in atrial myocardium in group 2 (D) than in group 1 (C). E and F, Trichrome staining demonstrating similar connective tissue distributions between group 1 (E) and group 2 (F).
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5015371&req=5

jah31615-fig-0004: Examples of immunohistochemical (group 1: A and C, group 2: B and D) and trichrome staining (group 1: E, group 2: F) in cardiac ganglia and myocardia. A and B, Choline acetyltransferase (ChAT) staining showing increased cholinergic neural density within ganglia in group 2 (B) than in group 1 (A). C and D, Tyrosine hydroxylase (TH) staining showing increased sympathetic innervation in atrial myocardium in group 2 (D) than in group 1 (C). E and F, Trichrome staining demonstrating similar connective tissue distributions between group 1 (E) and group 2 (F).

Mentions: Four GPs and myocardia from the anterior wall of the LA and RA were harvested in group 1 and 2 dogs after the second operation. In group 3 dogs, without undergoing thoracotomy or RAP, animals were killed to provide baseline histological data for comparison. Figure 4 illustrates examples of the histological studies from the fat pad containing GPs with ChAT staining and myocardia with TH and trichrome staining in group 1 (A, C, and E) and group 2 (B, D, and F) dogs. In the GPs, group 1 dogs demonstrated a lower ChAT‐positive nerve density (236.55±19.04 103 μm2/mm2) than that of the group 2 dogs (359.92±16.45 103 μm2/mm2, P<0.001) but similar to that of the group 3 dogs (218.76±11.02 103 μm2/mm2, P=NS). The GP TH‐positive nerve density of group 1 dog was 166.02±19.59 103 μm2/mm2 and was similar to that of group 2 dogs (163.25±20.35 103 μm2/mm2, P=NS) and group 3 dogs (130.07±14.33 103 μm2/mm2, P=NS), respectively. Individual GP immunohistochemistry staining results are shown in Figure 5. In the atrial myocardium, there was a higher TH‐positive nerve density in group 2 (16.07±2.26 103 μm2/mm2) than in group 1 (1.01±0.30 103 μm2/mm2, P<0.001) and group 3 (0.96±0.28 103 μm2/mm2, P<0.001), respectively, but there was no difference between group 1 and group 3 (Figure 5D). The ChAT‐positive nerve densities were comparable among 3 groups (0.44±0.15 and 0.40±0.11 versus 0.39±0.25 μm2/mm2, P=0.36) in the atrial myocardium (Figure 5C).


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 ”
Examples of immunohistochemical (group 1: A and C, group 2: B and D) and trichrome staining (group 1: E, group 2: F) in cardiac ganglia and myocardia. A and B, Choline acetyltransferase (ChAT) staining showing increased cholinergic neural density within ganglia in group 2 (B) than in group 1 (A). C and D, Tyrosine hydroxylase (TH) staining showing increased sympathetic innervation in atrial myocardium in group 2 (D) than in group 1 (C). E and F, Trichrome staining demonstrating similar connective tissue distributions between group 1 (E) and group 2 (F).
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

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

jah31615-fig-0004: Examples of immunohistochemical (group 1: A and C, group 2: B and D) and trichrome staining (group 1: E, group 2: F) in cardiac ganglia and myocardia. A and B, Choline acetyltransferase (ChAT) staining showing increased cholinergic neural density within ganglia in group 2 (B) than in group 1 (A). C and D, Tyrosine hydroxylase (TH) staining showing increased sympathetic innervation in atrial myocardium in group 2 (D) than in group 1 (C). E and F, Trichrome staining demonstrating similar connective tissue distributions between group 1 (E) and group 2 (F).
Mentions: Four GPs and myocardia from the anterior wall of the LA and RA were harvested in group 1 and 2 dogs after the second operation. In group 3 dogs, without undergoing thoracotomy or RAP, animals were killed to provide baseline histological data for comparison. Figure 4 illustrates examples of the histological studies from the fat pad containing GPs with ChAT staining and myocardia with TH and trichrome staining in group 1 (A, C, and E) and group 2 (B, D, and F) dogs. In the GPs, group 1 dogs demonstrated a lower ChAT‐positive nerve density (236.55±19.04 103 μm2/mm2) than that of the group 2 dogs (359.92±16.45 103 μm2/mm2, P<0.001) but similar to that of the group 3 dogs (218.76±11.02 103 μm2/mm2, P=NS). The GP TH‐positive nerve density of group 1 dog was 166.02±19.59 103 μm2/mm2 and was similar to that of group 2 dogs (163.25±20.35 103 μm2/mm2, P=NS) and group 3 dogs (130.07±14.33 103 μm2/mm2, P=NS), respectively. Individual GP immunohistochemistry staining results are shown in Figure 5. In the atrial myocardium, there was a higher TH‐positive nerve density in group 2 (16.07±2.26 103 μm2/mm2) than in group 1 (1.01±0.30 103 μm2/mm2, P<0.001) and group 3 (0.96±0.28 103 μm2/mm2, P<0.001), respectively, but there was no difference between group 1 and group 3 (Figure 5D). The ChAT‐positive nerve densities were comparable among 3 groups (0.44±0.15 and 0.40±0.11 versus 0.39±0.25 μm2/mm2, P=0.36) in the atrial myocardium (Figure 5C).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Botulinum toxin (BTX), temporarily suppressing cholinergic transmission (&lt;3&nbsp;weeks), has been reported to suppress atrial fibrillation (AF) for &ge;1&nbsp;year. We aimed to investigate the mechanism underlying long&#8208;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&nbsp;bpm) 6&nbsp;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&nbsp;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&#8208;term suppression of AF, indicating the critical role of GPs in AF progression.

No MeSH data available.


Related in: MedlinePlus