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In-depth characterization of a mouse model of postoperative atrial fibrillation

INTRODUCTION: Postoperative atrial fibrillation (POAF), characterized as AF that arises 1-3 days after surgery, occurs after 30%-40% of cardiac and 10%-20% of non-cardiac surgeries, and is thought to arise due to transient surgery-induced triggers acting on a preexisting vulnerable atrial substrate...

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Autores principales: Keefe, Joshua A., Navarro-Garcia, Jose Alberto, Ni, Li, Reilly, Svetlana, Dobrev, Dobromir, Wehrens, Xander H. T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632544/
https://www.ncbi.nlm.nih.gov/pubmed/36337729
http://dx.doi.org/10.20517/jca.2022.21
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author Keefe, Joshua A.
Navarro-Garcia, Jose Alberto
Ni, Li
Reilly, Svetlana
Dobrev, Dobromir
Wehrens, Xander H. T.
author_facet Keefe, Joshua A.
Navarro-Garcia, Jose Alberto
Ni, Li
Reilly, Svetlana
Dobrev, Dobromir
Wehrens, Xander H. T.
author_sort Keefe, Joshua A.
collection PubMed
description INTRODUCTION: Postoperative atrial fibrillation (POAF), characterized as AF that arises 1-3 days after surgery, occurs after 30%-40% of cardiac and 10%-20% of non-cardiac surgeries, and is thought to arise due to transient surgery-induced triggers acting on a preexisting vulnerable atrial substrate often associated with inflammation and autonomic nervous system dysfunction. Current experimental studies often rely on human atrial tissue samples, collected during surgery prior to arrhythmia development, or animal models such as sterile pericarditis and atriotomy, which have not been robustly characterized. AIM: To characterize the demographic, electrophysiologic, and inflammatory properties of a POAF mouse model. METHODS AND RESULTS: A total of 131 wild-type C57BL/6J mice were included in this study. A total of 86 (65.6%) mice underwent cardiothoracic surgery (THOR), which consisted of bi-atrial pericardiectomy with 20 s of aortic cross-clamping; 45 (34.3%) mice underwent a sham procedure consisting of dissection down to but not into the thoracic cavity. Intracardiac pacing, performed 72 h after surgery, was used to assess AF inducibility. THOR mice showed greater AF inducibility (38.4%) compared to Sham mice (17.8%, P = 0.027). Stratifying the cohort by tertiles of age showed that the greatest risk of POAF after THOR compared to Sham occurred in the 12-19-week age group. Stratifying by sex showed that cardiothoracic (CT) surgery increased POAF risk in females but had no significant effect in males. Quantitative polymerase chain reaction of atrial samples revealed upregulation of transforming growth factor beta 1 (TGF-β1) and interleukin 6 (IL6) and 18 (IL18) expression in THOR compared to Sham mice. CONCLUSION: Here, we demonstrate that the increased POAF risk associated with CT surgery is most pronounced in female and 12-19-week-old mice, and that the expression of inflammatory cytokines is upregulated in the atria of THOR mice prone to inducible AF.
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spelling pubmed-96325442022-11-03 In-depth characterization of a mouse model of postoperative atrial fibrillation Keefe, Joshua A. Navarro-Garcia, Jose Alberto Ni, Li Reilly, Svetlana Dobrev, Dobromir Wehrens, Xander H. T. J Cardiovasc Aging Article INTRODUCTION: Postoperative atrial fibrillation (POAF), characterized as AF that arises 1-3 days after surgery, occurs after 30%-40% of cardiac and 10%-20% of non-cardiac surgeries, and is thought to arise due to transient surgery-induced triggers acting on a preexisting vulnerable atrial substrate often associated with inflammation and autonomic nervous system dysfunction. Current experimental studies often rely on human atrial tissue samples, collected during surgery prior to arrhythmia development, or animal models such as sterile pericarditis and atriotomy, which have not been robustly characterized. AIM: To characterize the demographic, electrophysiologic, and inflammatory properties of a POAF mouse model. METHODS AND RESULTS: A total of 131 wild-type C57BL/6J mice were included in this study. A total of 86 (65.6%) mice underwent cardiothoracic surgery (THOR), which consisted of bi-atrial pericardiectomy with 20 s of aortic cross-clamping; 45 (34.3%) mice underwent a sham procedure consisting of dissection down to but not into the thoracic cavity. Intracardiac pacing, performed 72 h after surgery, was used to assess AF inducibility. THOR mice showed greater AF inducibility (38.4%) compared to Sham mice (17.8%, P = 0.027). Stratifying the cohort by tertiles of age showed that the greatest risk of POAF after THOR compared to Sham occurred in the 12-19-week age group. Stratifying by sex showed that cardiothoracic (CT) surgery increased POAF risk in females but had no significant effect in males. Quantitative polymerase chain reaction of atrial samples revealed upregulation of transforming growth factor beta 1 (TGF-β1) and interleukin 6 (IL6) and 18 (IL18) expression in THOR compared to Sham mice. CONCLUSION: Here, we demonstrate that the increased POAF risk associated with CT surgery is most pronounced in female and 12-19-week-old mice, and that the expression of inflammatory cytokines is upregulated in the atria of THOR mice prone to inducible AF. 2022 2022-07-19 /pmc/articles/PMC9632544/ /pubmed/36337729 http://dx.doi.org/10.20517/jca.2022.21 Text en https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Keefe, Joshua A.
Navarro-Garcia, Jose Alberto
Ni, Li
Reilly, Svetlana
Dobrev, Dobromir
Wehrens, Xander H. T.
In-depth characterization of a mouse model of postoperative atrial fibrillation
title In-depth characterization of a mouse model of postoperative atrial fibrillation
title_full In-depth characterization of a mouse model of postoperative atrial fibrillation
title_fullStr In-depth characterization of a mouse model of postoperative atrial fibrillation
title_full_unstemmed In-depth characterization of a mouse model of postoperative atrial fibrillation
title_short In-depth characterization of a mouse model of postoperative atrial fibrillation
title_sort in-depth characterization of a mouse model of postoperative atrial fibrillation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632544/
https://www.ncbi.nlm.nih.gov/pubmed/36337729
http://dx.doi.org/10.20517/jca.2022.21
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