Jiang Li-Ping, Lin Jing-Jing, Zhuang Ting-Pei, Wang Wei-Wei, Wu Hang-Zhou, Zhang Fei-Long
Department of General Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.
Department of Cardiology, Fujian Medical University Union Hospital and Fujian Provincial Institute of Coronary Disease, Fuzhou, China.
Arch Med Sci. 2020 Nov 23;19(5):1497-1507. doi: 10.5114/aoms.2020.101181. eCollection 2023.
This study aims to investigate the effects of ivabradine (IVA) on ventricular electrophysiological remodeling after myocardial infarction (MI) in rats.
A total of 60 male Sprague-Dawley rats were randomly divided into five groups: an MI group, an IVA group, a metoprolol (MET) group, an IVA + MET group, and a sham group. After a four-week intervention, the ventricular electrophysiological parameters were detected by multichannel electrophysiological polygraph. Then, the morphological characteristics were evaluated using hematoxylin and eosin (H&E) and Masson's staining, and the expression of phosphorylated connexin 43 (p-Cx43) in the left ventricular wall was detected through immunohistochemistry and the Western blot test.
The electrophysiological examination revealed that the induction rate and fatality rate of ventricular tachycardia (VT)/ventricular fibrillation (VF) were lower in both the IVA and the MET group, compared with the MI group (6/12, 6/12 vs. 10/11; and 1/12, 1/12 vs. 5/11; all < 0.05), as well as the IVA + MET group (1/11 vs. 10/11, < 0.01; and 1/11 vs. 5/11, < 0.05). The induction rate of VT/VF was lower in the IVA + MET group, compared to the MET group (1/11 s. 6/12, < 0.05). H&E and Masson's staining revealed that compared with the MI group, the left ventricular infarction area was lower in the IVA, MET, and IVA + MET groups ( < 0.05, < 0.05, and < 0.01, respectively), while collagen volume fraction (CVF) also was lower in the other groups (all < 0.01). The left ventricular infarction area and CVF both were lower in the IVA + MET group, compared to the MET group ( < 0.05 and < 0.01, respectively). The immunohistochemistry and Western blot revealed that p-Cx43 expression was higher in the treatment groups, compared with the MI group (all < 0.01).
IVA can reduce the incidence of ventricular arrhythmia after MI in male rats by improving both structural and electrical remodeling, and the combination of IVA and MET is even more effective.
本研究旨在探讨伊伐布雷定（IVA）对大鼠心肌梗死（MI）后心室电生理重构的影响。
将60只雄性Sprague-Dawley大鼠随机分为五组：心肌梗死组、伊伐布雷定组、美托洛尔（MET）组、伊伐布雷定+美托洛尔组和假手术组。经过四周干预后，采用多通道电生理记录仪检测心室电生理参数。然后，使用苏木精-伊红（H&E）染色和Masson染色评估形态学特征，并通过免疫组织化学和蛋白质印迹试验检测左心室壁中磷酸化连接蛋白43（p-Cx43）的表达。
电生理检查显示，与心肌梗死组相比，伊伐布雷定组和美托洛尔组室性心动过速（VT）/心室颤动（VF）的诱发率和死亡率均较低（6/12，6/12对10/11；以及1/12，1/12对5/11；均<0.05），伊伐布雷定+美托洛尔组也是如此（1/11对10/11，<0.01；以及1/11对5/11，<0.05）。与美托洛尔组相比，伊伐布雷定+美托洛尔组VT/VF的诱发率较低（1/11对6/12，<0.05）。H&E染色和Masson染色显示，与心肌梗死组相比，伊伐布雷定组、美托洛尔组和伊伐布雷定+美托洛尔组的左心室梗死面积均较低（分别为<0.05、<0.05和<0.01），而其他组的胶原容积分数（CVF）也较低（均<0.01）。与美托洛尔组相比，伊伐布雷定+美托洛尔组的左心室梗死面积和CVF均较低（分别为<0.05和<0.01）。免疫组织化学和蛋白质印迹试验显示，与心肌梗死组相比，治疗组中p-Cx43的表达较高（均<0.01）。
伊伐布雷定可通过改善结构和电重构降低雄性大鼠心肌梗死后室性心律失常的发生率，伊伐布雷定与美托洛尔联合使用效果更佳。
