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Atrial Fibrillation Promotion by Endurance Exercise
Open accessAbstract
Objectives The goal of this study was to assess mechanisms underlying atrial fibrillation (AF) promotion by exercise training in an animal model.Background High-level exercise training promotes AF, but the underlying mechanisms are unclear.Methods AF susceptibility was assessed by programmed stimulation in rats after 8 (Ex8) and 16 (Ex16) weeks of daily 1-h treadmill training, along with 4 and 8 weeks after exercise cessation and time-matched sedentary (Sed) controls. Structural remodeling was evaluated by using serial echocardiography and histopathology, autonomic nervous system with pharmacological tools, acetylcholine-regulated potassium current (IKACh) with patch clamp recording, messenger ribonucleic acid expression with quantitative polymerase chain reaction, and regulators of G protein-signaling (RGS) 4 function in knockout mice.Results AF inducibility increased after 16 weeks of training (e.g., AF >30 s in 64% of Ex16 rats vs 15% of Sed rats; p < 0.01) and rapidly returned to baseline levels with detraining. Atropine restored sinus rhythm in 5 of 5 Ex rats with AF sustained >15 min. Atrial dilation and fibrosis developed after 16 weeks of training and failed to fully recover with exercise cessation. Parasympathetic tone was increased in Ex16 rats and normalized within 4 weeks of detraining. Baroreflex heart rate responses to phenylephrine-induced blood pressure elevation and IKACh sensitivity to carbachol were enhanced in Ex16 rats, implicating both central and end-organ mechanisms in vagal enhancement. Ex rats showed unchanged cardiac adrenergic and cholinergic receptor and IKACh-subunit gene expression, but significant messenger ribonucleic acid downregulation of IKACh-inhibiting RGS proteins was present at 16 weeks. RGS4 knockout mice showed significantly enhanced sensitivity to AF induction in the presence of carbachol.Conclusions Chronic endurance exercise increased AF susceptibility in rats, with autonomic changes, atrial dilation, and fibrosis identified as potential mechanistic contributors. Vagal promotion is particularly important and occurs via augmented baroreflex responsiveness and increased cardiomyocyte sensitivity to cholinergic stimulation, possibly due to RGS protein downregulation.
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“probably mediated by altered autonomic tone, volume load during exercise, atrial hypertrophy, and dilatation.903,904”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [904]
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“Detraining can reduce AF in models 904 and reduces ventricular arrhythmias in athletes, 907”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [904]
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Metadata
- Authors
- Guasch, E., Benito, B., Qi, X., Cifelli, C., Naud, P., Shi, Y., Mighiu, A., Tardif, J.-C., Tadevosyan, A., Chen, Y., Gillis, M.-A., Iwasaki, Y.-K., Dobrev, D., Mont, L., Heximer, S., & Nattel, S.
- Affiliations
- Montreal Heart Institute (CA)
- University of Toronto (CA)
- University of Duisburg-Essen (DE)
- Corresponding author
- Nattel, Stanley
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 62
- Issue
- 1
- Pages
- 68-77
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W199998949
- Cited by
- 302
- References
- 33
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 26 · 2023: 25 · 2022: 16 · 2021: 29 · 2020: 28 · 2019: 20 · 2018: 31 · 2017: 18 · 2016: 24 · 2015: 23 · 2014: 19 · 2013: 11
- FWCI
- 17.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Funders
- Canadian Institutes of Health Research (MGP-6957, MOP44365, MOP106670)
- Quebec Heart and Stroke Foundation
- Fondation Leducq
- Deutsche Forschungsgemeinschaft
- Spanish Health Ministry (CM08/00201, CM06/00189)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Keywords
- atrial fibrillation, endurance exercise, exercise training, atrial remodeling, atrial dilatation, atrial fibrosis, parasympathetic activity, vagal tone, baroreflex, RGS4, atrial fibrillation risk, detraining, atrial electrophysiology
- MeSH terms
- Animals, Atrial Fibrillation, Disease Models, Animal, Exercise Test, Mice, Inbred C57BL, Physical Conditioning, Animal, Physical Endurance, Random Allocation, Rats, Wistar, Mice, Knockout, Mice, Rats
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