Liang Xiaoyan, Shang Shuai, Bai Zechen, Wang Qing, Fan Yongqiang, Xiaokereti Jiasuoer, Lv Huasheng, Zhou Xianhui, Lu Yanmei, Tang Baopeng
Department of Pacing and Electrophysiology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China; Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China.
Department of Medical Engineering and Technology, Xinjiang Medical University, Xinjiang, China.
Anatol J Cardiol. 2024 Jul 16;28(9):429-36. doi: 10.14744/AnatolJCardiol.2024.3871.
Gap junction remodeling is an important cause of ventricular arrhythmia in heart failure. However, it remains unclear whether renal denervation (RDN) regulates gap junction remodeling in heart failure. To explore the effect of RDN on gap junction remodeling in dogs with high-pacing-induced heart failure.
Fifteen dogs were randomly divided into control (n = 5), heart failure (HF) (n = 5), and RDN+HF (n = 5) group. A high-pacing-induced-heart failure model was established using rapid right ventricular pacing for 4 weeks. The RDN+HF group underwent surgical and chemical ablation of both renal arteries before 4 weeks rapid right ventricular pacing. After 4 weeks, echocardiography, High-Performance Liquid Chromatography-Mass Spectrometry test for norepinephrine and epinephrine, and pathological analysis were performed in the above 3 groups. Further, immunohistochemical staining was used to detect tyrosine hydroxylase, ChaT, connexin 43 (Cx43), and connexin 40 (Cx40). Connexin 43 and Cx40 expression was detected by western blotting. Transmission electron microscopy was used to observe the gap junction.
Compared to the control group, myocardial fibrosis and sympathetic hyperactivity were observed in the HF group. Immunohistochemical staining and western blotting showed that Cx40 expression and Cx43 expression was significantly reduced in the HF group. Compared with the HF group, the RDN+HF group showed reduced sympathetic hyperactivity, Cx40 expression, Cx40/Cx43 ratio, and increased Cx43 expression.
Renal denervation alleviates gap junction remodeling in high-pacing-induced heart failure dogs.
缝隙连接重塑是心力衰竭时室性心律失常的重要原因。然而，肾去神经支配（RDN）是否调节心力衰竭时的缝隙连接重塑仍不清楚。本研究旨在探讨RDN对高频率起搏诱导的犬心力衰竭缝隙连接重塑的影响。
将15只犬随机分为对照组（n = 5）、心力衰竭组（HF，n = 5）和RDN + HF组（n = 5）。采用快速右心室起搏4周建立高频率起搏诱导的心力衰竭模型。RDN + HF组在快速右心室起搏4周前对双侧肾动脉进行手术和化学消融。4周后，对上述3组进行超声心动图检查、去甲肾上腺素和肾上腺素的高效液相色谱-质谱检测以及病理分析。此外，采用免疫组织化学染色检测酪氨酸羟化酶、胆碱乙酰转移酶、连接蛋白43（Cx43）和连接蛋白40（Cx40）。通过蛋白质印迹法检测Cx43和Cx40的表达。采用透射电子显微镜观察缝隙连接。
与对照组相比，HF组出现心肌纤维化和交感神经过度兴奋。免疫组织化学染色和蛋白质印迹法显示，HF组Cx40表达和Cx43表达显著降低。与HF组相比，RDN + HF组交感神经过度兴奋减轻，Cx40表达、Cx40/Cx43比值降低，Cx43表达增加。
肾去神经支配可减轻高频率起搏诱导的心力衰竭犬的缝隙连接重塑。
