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Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high frequency stimulation

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Title: Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high frequency stimulation
Authors: Kim, MY
Nesbitt, J
Koutsoftidis, S
Brook, J
Pitcher, D
Cantwell, C
Handa, B
Jenkins, C
Houston, C
Rothery, S
Jothidasan, A
Perkins, J
Bristow, P
Linton, N
Drakakis, E
Peters, N
Chowdhury, R
Kanagaratnam, P
Ng, FS
Item Type: Journal Article
Abstract: Introduction: The response to high frequency stimulation (HFS) is used to locate putative sites of ganglionated plexuses (GPs), which are implicated in triggering atrial fibrillation (AF). Objective: To identify topological and immunohistochemical characteristics of presumed GP sites functionally identified by HFS. Methods: 63 atrial sites were tested with HFS in 4 Langendorff-perfused porcine hearts. A 3.5mm tip quadripolar ablation catheter was used to stimulate and deliver HFS to the left and right atrial epicardium, within the local atrial refractory period. Tissue samples from sites triggering atrial ectopy/AF (ET) sites and non-ET sites were stained with choline acetyl transferase (ChAT) and tyrosine hydroxylase (TH), for quantification of parasympathetic and sympathetic nerves, respectively. The average cross-sectional area (CSA) of nerves was also calculated. Results: Histomorphometry of 6 ET sites (9.5%) identified by HFS evoking at least a single atrial ectopic was compared with non-ET sites. All ET sites contained ChAT-immunoreactive (ChAT-IR) and/or TH-immunoreactive nerves (TH-IR). Nerve density was greater in ET sites compared to non-ET sites (nerves/cm2: 162.3 ±110.9 vs 69.65 ±72.48; p=0.047). Overall, TH-IR nerves had larger CSA than ChAT-IR nerves (µm2: 11,196 ± 35,141 vs 2,070 ± 5,841; p<0.0001), but in ET sites, TH-IR nerves were smaller than in non-ET sites (µm2: 6,021±14,586 vs 25,254 ± 61,499; p<0.001). Conclusions: ET sites identified by HFS contained higher density of smaller nerves than non-ET sites. Majority of these nerves were within the atrial myocardium. This has important clinical implications on devising an effective therapeutic strategy for targeting autonomic triggers of AF.
Issue Date: 1-Feb-2023
Date of Acceptance: 19-Aug-2022
URI: http://hdl.handle.net/10044/1/99873
DOI: 10.1093/europace/euac176
ISSN: 1099-5129
Publisher: Oxford University Press
Start Page: 726
End Page: 738
Journal / Book Title: EP Europace
Volume: 25
Issue: 2
Copyright Statement: @ The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
Publication Status: Published
Online Publication Date: 2022-10-19
Appears in Collections:Bioengineering
National Heart and Lung Institute
Faculty of Medicine
Faculty of Engineering

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