title: Chronic obstructive sleep apnea causes atrial remodeling in canines: mechanisms and implications.
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 (IK1), delayed rectifier K(+) current (IKr and IKs), acetylcholine activated K(+) current (IKACh), transient outward K(+) current (Ito) and ultra-rapid delayed rectifier potassium current (IKur) as well as downregulation of protein encoding L-type Ca(2+) current (ICa,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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Youzheng Street 23#, Nangang District, Harbin, 150001, Heilongjiang, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Yun
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhao
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Li
authors.forename: Yongtai
authors.initials: Y
authors.lastname: Gong
authors.forename: Yue
authors.initials: Y
authors.lastname: Yuan
authors.forename: Sen
authors.initials: S
authors.lastname: Yan
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Ding
authors.forename: Dingyu
authors.initials: D
authors.lastname: Wang
authors.forename: Chaowei
authors.initials: C
authors.lastname: Zhang
authors.forename: Deli
authors.initials: D
authors.lastname: Dong
authors.forename: Chunhong
authors.initials: C
authors.lastname: Xiu
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Jingyi
authors.initials: J
authors.lastname: Xue
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D064752:Atrial Remodeling; D015153:Blotting, Western; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D004594:Electrophysiology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D046529:Microscopy, Electron, Transmission; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000503:physiopathology*