Metoprolol prevents chronic obstructive sleep apnea-induced atrial fibrillation by inhibiting structural, sympathetic nervous and metabolic remodeling of the atria.
Metoprolol prevents chronic obstructive sleep apnea-induced atrial fibrillation by inhibiting structural, sympathetic nervous and metabolic remodeling of the atria.
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美托洛尔通过抑制心房的结构、交感神经和代谢重塑来预防慢性阻塞性睡眠呼吸暂停引起的心房颤动
DOI：
10.1038/s41598-017-14960-2
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发表时间：
2017-11-02
影响因子：
4.6
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Sun L;Yan S;Wang X;Zhao S;Li H;Wang Y;Lu S;Dong X;Zhao J;Yu S;Li M;Li Y
慢性阻塞性睡眠呼吸暂停（OSA）可能通过诱发心房电重构和结构重构以及自主神经过度支配而促进心房颤动（AF）的发生。在此，我们研究了美托洛尔在慢性阻塞性睡眠呼吸暂停引起的心房重构中的作用。停用呼吸机，每隔一天关闭气道4 h/d，连续12周给予美托洛尔（5 mg·kg-1·day-1），建立慢性阻塞性睡眠呼吸暂停犬模型。通过该模型，我们观察到，美托洛尔显著抑制了交感神经萌芽和心房结构重构的增加。此外，美托洛尔通过激活Sirt1-AMPK通路显著抑制心房能代谢损伤。在体外，美托洛尔在间歇性缺氧和异丙肾上腺素处理的HL-1细胞中显著激活Sirt1- ampk通路，同时给药Sirt1激活抑制剂EX-527可消除这一作用。综上所述，美托洛尔对慢性osa诱导的心房重构具有保护作用。我们的研究结果为OSA诱发AF提供了一种新的可行的治疗策略。
Chronic obstructive sleep apnea (OSA) may promote the development of atrial fibrillation (AF) by inducing atrial electrical and structural remodeling as well as autonomic nerve hyperinnervation. Here, we investigated the roles of metoprolol in regulation of atrial remodeling induced by chronic OSA. A canine model of chronic OSA was established by stopping the ventilator and closing the airway for 4 h/day every other day for 12 weeks, while metoprolol (5 mg·kg-1·day-1) was continuously administered. Using that model, we observed that increases in sympathetic sprouting and atrial structural remodeling were sharply inhibited by metoprolol. Moreover, metoprolol dramatically inhibited the impairment of atrial energy metabolism by activating the Sirt1-AMPK pathway. In vitro, metoprolol significantly activated the Sirt1-AMPK pathway in intermittent hypoxic and isoproterenol-treated HL-1 cells, and the effect was abolished by the coadministration of EX-527, an inhibitor of Sirt1 activation. In summary, metoprolol protects against chronic OSA-induced atrial remodeling. Our results suggest a new and feasible treatment strategy for AF induced by OSA.
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影响因子：
9.1
作者：
Caples, Sean M.;Somers, Virend K.
通讯作者：
Somers, Virend K.
影响因子：
3
作者：
MAYER, J;WEICHLER, U;PETER, JH
通讯作者：
PETER, JH
影响因子：
--
作者：
Mehra, Reena;Stone, Katie L.;Varosy, Paul D.;Hoffman, Andrew R.;Marcus, Gregory M.;Blackwell, Terri;Ibrahim, Osama A.;Salem, Rawan;Redline, Susan
通讯作者：
Redline, Susan
影响因子：
4.3
作者：
Latina JM;Estes NA 3rd;Garlitski AC
通讯作者：
Garlitski AC
影响因子：
9.5
作者：
Li, Yue;Li, Wei-min;Yang, Bao-feng
通讯作者：
Yang, Bao-feng