Atrial Fibrillation Promotion by Endurance Exercise Demonstration and Mechanistic Exploration in an Animal Model

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:62

Article

Guasch, Eduard^1,2,3,4  Benito, Begona^1,2,3,4,5  Qi, Xiaoyan^1,2,3  Cifelli, Carlo^6,7  Naud, Patrice^1,2,3  Shi, Yanfen^1,2,3  Mighiu, Alexandra^6,7  Tardif, Jean-Claude^1,2,3  Tadevosyan, Artavazd^1,2,3  Chen, Yu^1,2,3  Gillis, Marc-Antoine^1,2,3  Iwasaki, Yu-Ki^1,2,3  Dobrev, Dobromir⁸  Mont, Lluis^6,7,9  Heximer, Scott^6,7  Nattel, Stanley^1,2,3 

[1] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada

[2] Montreal Heart Inst, Dept Med, Montreal, PQ H1T 1C8, Canada

[3] Univ Montreal, Montreal, PQ H1T 1C8, Canada

[4] Univ Barcelona, Dept Med, Barcelona, Catalonia, Spain

[5] Hosp Mar, Dept Cardiol, Barcelona, Catalonia, Spain

[6] Heart & Stroke Richard Lewar Ctr Excellence Cardi, Dept Physiol, Toronto, ON, Canada

[7] Univ Toronto, Toronto, ON, Canada

[8] Univ Duisburg Essen, Inst Pharmacol, Essen, Germany

[9] Univ Barcelona, Unitat Fibrillacio Auricular, Hosp Clin, IDIBAPS, Barcelona, Catalonia, Spain

关键词: arrhythmia mechanisms;    exercise training;    ion currents;    potassium channel;   

DOI  :  10.1016/j.jacc.2013.01.091

来源: Elsevier

【 摘 要 】

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 (I-KACh) 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 I-KACh 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 I-KACh-subunit gene expression, but significant messenger ribonucleic acid downregulation of I-KACh-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. (C) 2013 by the American College of Cardiology Foundation

【 授权许可】

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