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01-09-2014 | Original Contribution

Chronic obstructive sleep apnea causes atrial remodeling in canines: mechanisms and implications

Authors: Jing Zhao, Wei Xu, Fengxiang Yun, Hongwei Zhao, Wenpeng Li, Yongtai Gong, Yue Yuan, Sen Yan, Song Zhang, Xue Ding, Dingyu Wang, Chaowei Zhang, Deli Dong, Chunhong Xiu, Ning Yang, Lei Liu, Jingyi Xue, Yue Li

Published in: Basic Research in Cardiology | Issue 5/2014

Abstract

Obstructive sleep apnea (OSA) is closely related to atrial fibrillation (AF). However, the roles and mechanisms of chronic OSA in atrial remodeling are still unclear. Canine model of chronic OSA was simulated by stopping the ventilator and closing the airway for 4 h per day and lasting for 12 weeks. AF inducibility and duration was increased while atrial effective refractory period (AERP) was shortened after chronic apnea. Meanwhile, upregulation of proteins encoding inward rectifier K⁺ current (I _K1), delayed rectifier K⁺ current (I _Kr and I _Ks), acetylcholine activated K⁺ current (I _KACh), transient outward K⁺ current (I _to) and ultra-rapid delayed rectifier potassium current (I _Kur) as well as downregulation of protein encoding L-type Ca²⁺ current (I _Ca,L) were found after chronic OSA. Besides abnormal electrical activity, chronic OSA induced apoptosis and interstitial fibrosis of atrial myocytes, which was partly mediated by caspase 9, phosphorylation of extracellular-regulated kinase 1/2, and α-smooth muscle actin. In addition, atrial sympathetic and parasympathetic hyperinnervation were found manifesting by enhanced growth-associated protein 43, tyrosine hydroxylase and elevated choline acetyltransferase. Moreover, protein expression of β₁, β₂, and M₂ receptor were markedly increased by chronic OSA. In summary, we firstly demonstrated in canine model that chronic OSA could shorten AERP and lead to altered expression of important channel proteins, moreover, induce atrial structure remodeling by increased atrial apoptosis, fibrosis, and autonomic remodeling, eventually promoting the development of a substrate of AF. Our findings suggested that reversing atrial remodeling might be a potential therapeutic strategy for OSA-induced AF.

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Title: Chronic obstructive sleep apnea causes atrial remodeling in canines: mechanisms and implications
Authors: Jing Zhao
Wei Xu
Fengxiang Yun
Hongwei Zhao
Wenpeng Li
Yongtai Gong
Yue Yuan
Sen Yan
Song Zhang
Xue Ding
Dingyu Wang
Chaowei Zhang
Deli Dong
Chunhong Xiu
Ning Yang
Lei Liu
Jingyi Xue
Yue Li
Publication date: 01-09-2014
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 5/2014
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-014-0427-8

2024 ASCO Annual Meeting

Springer Medicine

Chronic obstructive sleep apnea causes atrial remodeling in canines: mechanisms and implications

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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