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左侧非侵入性迷走神经刺激通过上调犬心房缝隙连接抑制心房颤动。

Left-sided Noninvasive Vagus Nerve Stimulation Suppresses Atrial Fibrillation by Upregulating Atrial Gap Junctions in Canines.

作者信息

Chen Mingxian, Zhou Xiaoya, Liu Qiming, Sheng Xia, Yu Lilei, Wang Zhuo, Wang Songyun, Zhou Shenghua

机构信息

*Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; †Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, Hubei, China; and ‡Department of Cardiology, Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University, Hangzhou, China.

出版信息

J Cardiovasc Pharmacol. 2015 Dec;66(6):593-9. doi: 10.1097/FJC.0000000000000309.

DOI:10.1097/FJC.0000000000000309
PMID:26317165
Abstract

BACKGROUND

We have previously shown that right-sided low-level tragus nerve stimulation (LL-TS) is an effective approach for the treatment of atrial fibrillation (AF) induced by rapid atrial pacing (RAP) and acts by preventing the loss of atrial connexins (Cxs). Whether a left-sided approach would achieve the same effect remains unknown.

OBJECTIVE

We hypothesized that left-sided LL-TS would inhibit AF by preserving atrial Cxs as effectively as right-sided LL-TS.

METHODS

Bilateral thoracotomies allowed the attachment of multielectrode catheters to the pulmonary vein and non-pulmonary vein sites in 32 anaesthetized beagles. The dogs were randomly divided into 3 groups: RAP group (9 hours of RAP at the left appendage, n = 10), LL-TS group (9-hour RAP plus LL-TS, n = 12), and control group (sham RAP without LL-TS, n = 10). Alligator clips were clipped on the tragus of the left ear for electrical stimulation (20 Hz, 1 millisecond square waves). A voltage of stimulation setting at 80% below the threshold that slowed the sinus rate was defined as LL-TS. Electrophysiological parameters were measured at baseline and 9 hours after pacing. Connexin proteins from atrial tissues were measured at the end of the protocol.

RESULTS

RAP induced a significant reduction in the effective refractory period and an increase in AF inducibility (P < 0.05). However, left-sided LL-TS reversed the effective refractory period reduction induced by RAP and the increase in AF inducibility. It also shortened the AF duration and prolonged the AF cycle length, which are associated with Cx40 and Cx43 upregulation (P < 0.05).

CONCLUSIONS

We propose that left-sided LL-TS exerts its anti-AF effects through upregulation of Cxs as effectively as right-sided LL-TS, suggesting that LL-TS for AF suppression is not unique to the right tragus nerve.

摘要

背景

我们之前已经表明,右侧低水平耳屏神经刺激(LL-TS)是治疗快速心房起搏(RAP)诱发的心房颤动(AF)的一种有效方法,其作用机制是防止心房连接蛋白(Cxs)的丢失。左侧刺激方法是否能达到相同效果仍不清楚。

目的

我们假设左侧LL-TS能像右侧LL-TS一样有效地通过保留心房Cxs来抑制AF。

方法

对32只麻醉的比格犬进行双侧开胸手术,将多电极导管连接到肺静脉和非肺静脉部位。这些犬被随机分为3组:RAP组(在左心耳进行9小时的RAP,n = 10)、LL-TS组(9小时的RAP加LL-TS,n = 12)和对照组(假RAP,无LL-TS,n = 10)。将鳄鱼夹夹在左耳耳屏上进行电刺激(20 Hz,1毫秒方波)。将刺激电压设置为低于减慢窦性心率阈值80%的电压定义为LL-TS。在起搏前基线和起搏9小时后测量电生理参数。在实验结束时测量心房组织中的连接蛋白。

结果

RAP导致有效不应期显著缩短,房颤诱发率增加(P < 0.05)。然而,左侧LL-TS逆转了RAP引起的有效不应期缩短和房颤诱发率增加。它还缩短了房颤持续时间,延长了房颤周期长度,这与Cx40和Cx43上调有关(P < 0.05)。

结论

我们提出左侧LL-TS与右侧LL-TS一样,通过上调Cxs发挥抗AF作用,这表明用于抑制AF的LL-TS并非右侧耳屏神经所特有。

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