Huo Jun-Yu, Jiang Wan-Ying, Chen Chu, Chen Ran, Ge Tian-Tian, Chang Qing, Zhu Lin, Geng Jie, Jiang Zhi-Xin, Shan Qi-Jun
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University.
Int Heart J. 2019 Sep 27;60(5):1168-1175. doi: 10.1536/ihj.19-065. Epub 2019 Sep 4.
The aims of the present study were to investigate the effects of angiotensin receptor neprilysin inhibitors (ARNi) on the susceptibility of ventricular arrhythmias (VAs) in rats with myocardial infarction (MI) and to explore the related mechanisms.A total of 32 adult male Sprague-Dawley rats were divided into 3 groups: a control group, MI group, and MI+ARNi group. MI was generated by ligation of the left anterior descending coronary artery. ARNi was given at 68 mg/kg/day for 4 weeks after MI surgery. At 4 weeks after MI, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of VAs, and echocardiography was used to evaluate cardiac function. Indicators of sympathetic neural remodeling and cardiac remodeling were detected to further explore the related mechanisms.Four weeks after MI, rats in the ARNi group exhibited low susceptibility of VAs in comparison with that in the MI group, which was coincident with the attenuation of sympathetic nerve remodeling, amelioration of cardiac fibrosis, and regulation of Cx43 expression.ARNi is effective in reducing VAs in rats with ischemic cardiomyopathy, which is associated with attenuating sympathetic nerve remodeling and myocardial fibrosis.
本研究的目的是探讨血管紧张素受体脑啡肽酶抑制剂（ARNi）对心肌梗死（MI）大鼠室性心律失常（VA）易感性的影响，并探索其相关机制。将32只成年雄性Sprague-Dawley大鼠分为3组：对照组、MI组和MI+ARNi组。通过结扎左冠状动脉前降支制备MI模型。MI手术后，以68 mg/kg/天的剂量给予ARNi，持续4周。MI后4周，对所有组进行电程序刺激（EPS）以评估VA，并使用超声心动图评估心脏功能。检测交感神经重塑和心脏重塑指标以进一步探索相关机制。MI后4周，与MI组相比，ARNi组大鼠的VA易感性较低，这与交感神经重塑的减轻、心脏纤维化的改善和Cx43表达的调节相一致。ARNi可有效降低缺血性心肌病大鼠的VA，这与减轻交感神经重塑和心肌纤维化有关。
