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

AIMS: 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). To identify topological and immunohistochemical characteristics of presumed GP sites functionally identified by HFS. ME...

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Autores principales: Kim, Min-young, Nesbitt, James, Koutsoftidis, Simos, Brook, Joseph, Pitcher, David S, Cantwell, Chris D, Handa, Balvinder, Jenkins, Catherine, Houston, Charles, Rothery, Stephen, Jothidasan, Anand, Perkins, Justin, Bristow, Poppy, Linton, Nick W F, Drakakis, Emm, Peters, Nicholas S, Chowdhury, Rasheda A, Kanagaratnam, Prapa, Ng, Fu Siong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935019/
https://www.ncbi.nlm.nih.gov/pubmed/36260428
http://dx.doi.org/10.1093/europace/euac176
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author Kim, Min-young
Nesbitt, James
Koutsoftidis, Simos
Brook, Joseph
Pitcher, David S
Cantwell, Chris D
Handa, Balvinder
Jenkins, Catherine
Houston, Charles
Rothery, Stephen
Jothidasan, Anand
Perkins, Justin
Bristow, Poppy
Linton, Nick W F
Drakakis, Emm
Peters, Nicholas S
Chowdhury, Rasheda A
Kanagaratnam, Prapa
Ng, Fu Siong
author_facet Kim, Min-young
Nesbitt, James
Koutsoftidis, Simos
Brook, Joseph
Pitcher, David S
Cantwell, Chris D
Handa, Balvinder
Jenkins, Catherine
Houston, Charles
Rothery, Stephen
Jothidasan, Anand
Perkins, Justin
Bristow, Poppy
Linton, Nick W F
Drakakis, Emm
Peters, Nicholas S
Chowdhury, Rasheda A
Kanagaratnam, Prapa
Ng, Fu Siong
author_sort Kim, Min-young
collection PubMed
description AIMS: 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). To identify topological and immunohistochemical characteristics of presumed GP sites functionally identified by HFS. METHODS AND RESULTS: Sixty-three atrial sites were tested with HFS in four Langendorff-perfused porcine hearts. A 3.5 mm 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 acetyltransferase (ChAT) and tyrosine hydroxylase (TH), for quantification of parasympathetic and sympathetic nerves, respectively. The average cross-sectional area (CSA) of nerves was also calculated. Histomorphometry of six 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/cm(2): 162.3 ± 110.9 vs. 69.65 ± 72.48; P = 0.047). Overall, TH-IR nerves had a larger CSA than ChAT-IR nerves (µm(2): 11 196 ± 35 141 vs. 2070 ± 5841; P < 0.0001), but in ET sites, TH-IR nerves were smaller than in non-ET sites (µm(2): 6021 ± 14 586 vs. 25 254 ± 61 499; P < 0.001). CONCLUSIONS: ET sites identified by HFS contained a higher density of smaller nerves than non-ET sites. The majority of these nerves were within the atrial myocardium. This has important clinical implications for devising an effective therapeutic strategy for targeting autonomic triggers of AF.
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spelling pubmed-99350192023-02-17 Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high-frequency stimulation Kim, Min-young Nesbitt, James Koutsoftidis, Simos Brook, Joseph Pitcher, David S Cantwell, Chris D Handa, Balvinder Jenkins, Catherine Houston, Charles Rothery, Stephen Jothidasan, Anand Perkins, Justin Bristow, Poppy Linton, Nick W F Drakakis, Emm Peters, Nicholas S Chowdhury, Rasheda A Kanagaratnam, Prapa Ng, Fu Siong Europace Basic Science AIMS: 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). To identify topological and immunohistochemical characteristics of presumed GP sites functionally identified by HFS. METHODS AND RESULTS: Sixty-three atrial sites were tested with HFS in four Langendorff-perfused porcine hearts. A 3.5 mm 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 acetyltransferase (ChAT) and tyrosine hydroxylase (TH), for quantification of parasympathetic and sympathetic nerves, respectively. The average cross-sectional area (CSA) of nerves was also calculated. Histomorphometry of six 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/cm(2): 162.3 ± 110.9 vs. 69.65 ± 72.48; P = 0.047). Overall, TH-IR nerves had a larger CSA than ChAT-IR nerves (µm(2): 11 196 ± 35 141 vs. 2070 ± 5841; P < 0.0001), but in ET sites, TH-IR nerves were smaller than in non-ET sites (µm(2): 6021 ± 14 586 vs. 25 254 ± 61 499; P < 0.001). CONCLUSIONS: ET sites identified by HFS contained a higher density of smaller nerves than non-ET sites. The majority of these nerves were within the atrial myocardium. This has important clinical implications for devising an effective therapeutic strategy for targeting autonomic triggers of AF. Oxford University Press 2022-10-19 /pmc/articles/PMC9935019/ /pubmed/36260428 http://dx.doi.org/10.1093/europace/euac176 Text en @ The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Basic Science
Kim, Min-young
Nesbitt, James
Koutsoftidis, Simos
Brook, Joseph
Pitcher, David S
Cantwell, Chris D
Handa, Balvinder
Jenkins, Catherine
Houston, Charles
Rothery, Stephen
Jothidasan, Anand
Perkins, Justin
Bristow, Poppy
Linton, Nick W F
Drakakis, Emm
Peters, Nicholas S
Chowdhury, Rasheda A
Kanagaratnam, Prapa
Ng, Fu Siong
Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high-frequency stimulation
title Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high-frequency stimulation
title_full Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high-frequency stimulation
title_fullStr Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high-frequency stimulation
title_full_unstemmed Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high-frequency stimulation
title_short Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high-frequency stimulation
title_sort immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high-frequency stimulation
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935019/
https://www.ncbi.nlm.nih.gov/pubmed/36260428
http://dx.doi.org/10.1093/europace/euac176
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