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

Joshua A Keefe; Jose Alberto Navarro-Garcia; Li Ni; Svetlana Reilly; Dobromir Dobrev; Xander H T Wehrens

doi:10.20517/jca.2022.21

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

J Cardiovasc Aging. 2022:2:40. doi: 10.20517/jca.2022.21. Epub 2022 Jul 19.

Authors

Joshua A Keefe^{1

2}, Jose Alberto Navarro-Garcia^{1

2}, Li Ni³, Svetlana Reilly⁴, Dobromir Dobrev^{2

5

6}, Xander H T Wehrens^{1

2

7

8

9

10}

Affiliations

¹ Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.
² Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA.
³ Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
⁴ Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
⁵ Institute of Pharmacology, University Duisburg-Essen, Essen 45122, Germany.
⁶ Department of Medicine and Research Center, Montreal Heart Institute and Universite de Montreal, Montreal, QC H1T 1C8, Canada.
⁷ Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
⁸ Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
⁹ Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁰ Center for Space Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

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.

Keywords: Atrial fibrillation; biological sex; cardiothoracic surgery; fibrosis; inflammation.

Abstract

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