Efferent vagal nerve stimulation protects heart against ischemia-induced arrhythmias by preserving connexin43 protein
Efferent vagal nerve stimulation protects heart against ischemia-induced arrhythmias by preserving connexin43 protein
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DOI：
10.1161/circulationaha.104.525493
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发表时间：
2005-07-12
期刊：
影响因子：
37.8
通讯作者：
Sato, T
中科院分区：
文献类型：
--
作者：
Ando, M;Katare, RG;Sato, T
背景-心肌缺血（MI）导致细胞电稳定性紊乱和致死性心律失常的产生。迷走神经刺激被认为有助于抗纤颤作用。方法与结果：在麻醉状态下，Wistar大鼠进行30分钟左冠状动脉结扎术，迷走神经刺激（MI-VS组，n = 11）和假性刺激（MI-SS组，n = 12）。MI-SS组12只大鼠中有8只在LCA结扎30分钟时出现室性心动过速（VT）；另一方面，MI-VS组11只大鼠中只有1只发生VT（分别为67%和9%）。阿托品可消除迷走神经刺激的抗心律失常作用。免疫印迹显示，与假手术和假刺激组相比，MI-SS组磷酸化的连接蛋白43 （Cx43）的数量明显减少，而MI-VS组仅略有减少（37 +/- 20%对79 +/- 18%）。免疫组化证实迷走神经刺激可防止mi诱导的细胞间连接Cx43的丢失。此外，对大鼠原代培养心肌细胞的研究表明，乙酰胆碱可以有效地防止缺氧诱导的磷酸化Cx43的丢失，并改善细胞间通讯的丢失，这与Lucifer Yellow染料转移实验的结果一致。结论：迷走神经刺激具有抗心律失常作用，同时可预防急性心肌梗死期间磷酸化Cx43的丢失，因此在改善缺血引起的电不稳定中起关键作用。
Background - Myocardial ischemia (MI) leads to derangements in cellular electrical stability and the generation of lethal arrhythmias. Vagal nerve stimulation has been postulated to contribute to the antifibrillatory effect. Here, we suggest a novel mechanism for the antiarrhythmogenic properties of vagal stimulation during acute MI.Methods and Results - Under anesthesia, Wistar rats underwent 30 minutes of left coronary artery (LCA) ligation with vagal stimulation (MI-VS group, n = 11) and with sham stimulation (MI-SS group, n = 12). Eight of the 12 rats in the MI-SS group had ventricular tachyarrhythmia (VT) during 30-minute LCA ligation; on the other hand, VT occurred in only 1 of the 11 rats in the MI-VS group (67% versus 9%, respectively). Atropine administration abolished the antiarrhythmogenic effect of vagal stimulation. Immunoblotting revealed that the MI-SS group showed a marked reduction in the amount of phosphorylated connexin43 (Cx43), whereas the MI-VS group showed only a slight reduction compared with the sham operation and sham stimulation group (37 +/- 20% versus 79 +/- 18%). Immunohistochemistry confirmed that the MI-induced loss of Cx43 from intercellular junctions was prevented by vagal stimulation. In addition, studies with rat primary-cultured cardiomyocytes demonstrated that acetylcholine effectively prevented the hypoxia-induced loss of phosphorylated Cx43 and ameliorated the loss of cell-to-cell communication as determined by Lucifer Yellow dye transfer assay, which supports the in vivo results.Conclusions - Vagal nerve stimulation exerts antiarrhythmogenic effects accompanied by prevention of the loss of phosphorylated Cx43 during acute MI and thus plays a critical role in improving ischemia-induced electrical instability.