Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Disease, National Clinical Research Center for Interventional Medicine, Fudan University, Shanghai, 200032, China.
Department of Cardiology, Zhongshan Hospital (Xiamen), Fudan University, 668 Jinhu Road, Xiamen, 361015, China.
BMC Cardiovasc Disord. 2024 Oct 29;24(1):605. doi: 10.1186/s12872-024-04261-8.
The role of Na1.8 impacts in atrial fibrillation susceptibility after myocardial infarction remains only partially understood. We studied the effect of blocking Na1.8 in the cardiac ganglionated plexi (GP) on the atrial fibrillation inducibility and cardiac conduction in the myocardial infarction model.
Eighteen male beagles were randomly enrolled. Left anterior descending coronary artery was ligated to created myocardial infarction model. Four weeks after surgery, Na1.8 blocker A-803,467 (n = 9) or DMSO (n = 9, control) was injected into the four cardiac major GPs. Sinus rate, ventricular rate during atrial fibrillation, PR interval, atrial effective refractory period, atrial fibrillation duration and the cumulative window of atrial vulnerability were measured before and 60 min after A-803,467 injection.
Administration of A-803,467 significantly increased sinus rate, shortened PR interval and increased ventricular rate during atrial fibrillation compared to control. A-803,467 also significantly shortened atrial effective refractory period, prolonged atrial fibrillation duration and increased the cumulative window of atrial vulnerability. A-803,467 suppressed the slowing of heart rate response to high-frequency electrical stimulation of the anterior right GP, which was used as the surrogate marker for GP function. Double staining of ChAT and Na1.8 demonstrated colocalization of ChAT and Na1.8 in canine GPs.
Blocking Na1.8 in the cardiac GP may modulate atrial fibrillation inducibility and cardiac conduction after myocardial infarction, and the underlying mechanism may be associated with the regulation of the neural activity of the cardiac GP.
心肌梗死后心房颤动易感性中 Na1.8 影响的作用仍不完全清楚。我们研究了阻断心肌梗死后心脏神经节丛（GP）中的 Na1.8 对心房颤动易感性和心脏传导的影响。
18 只雄性比格犬被随机纳入。结扎左前降支冠状动脉以建立心肌梗死模型。手术后 4 周，将 Na1.8 阻滞剂 A-803,467（n=9）或 DMSO（n=9，对照组）注入四个心脏主要 GP。在 A-803,467 注射前后测量窦性心率、心房颤动时的心室率、PR 间期、心房有效不应期、心房颤动持续时间和心房易损窗口的累积时间。
与对照组相比，A-803,467 给药显著增加了窦性心率，缩短了 PR 间期，增加了心房颤动时的心室率。A-803,467 还显著缩短了心房有效不应期，延长了心房颤动持续时间，并增加了心房易损窗口的累积时间。A-803,467 抑制了高频电刺激前右 GP 时心率反应的减慢，这被用作 GP 功能的替代标志物。ChAT 和 Na1.8 的双重染色显示 ChAT 和 Na1.8 在犬 GP 中存在共定位。
阻断心脏 GP 中的 Na1.8 可能调节心肌梗死后的心房颤动易感性和心脏传导，其潜在机制可能与心脏 GP 神经活性的调节有关。
