Zeng Mengliu, Jiang Wanzhen, Tian Youjia, Hao Jie, Cao Zhenzhen, Liu Zhipei, Fu Chen, Zhang Peihua, Ma Jihua
Cardio-Electrophysiological Research Laboratory, Medical College of Wuhan University of Science and Technology, Wuhan, Hubei, China.
Oncotarget. 2017 May 22;8(37):61226-61238. doi: 10.18632/oncotarget.18051. eCollection 2017 Sep 22.
Andrographolide has a protective effect on the cardiovascular system. To study its cardic-electrophysiological effects, action potentials and voltage-gated Na (I), Ca (I), and K (I, I, I and I) currents were recorded using whole-cell patch clamp and current clamp techniques. Additionally, the effects of andrographolide on aconitine-induced arrhythmias were assessed on electrocardiograms . We found that andrographolide shortened action potential duration and reduced maximum upstroke velocity in rabbit left ventricular and left atrial myocytes. Andrographolide attenuated rate-dependence of action potential duration, and reduced or abolished delayed afterdepolarizations and triggered activities induced by isoproterenol (1 μM) and high calcium ([Ca]=3.6 mM) in left ventricular myocytes. Andrographolide also concentration-dependently inhibited I and I, but had no effect on I, I, I, or I in rabbit left ventricular and left atrial myocytes. Andrographolide treatment increased the time and dosage thresholds of aconitine-induced arrhythmias, and reduced arrhythmia incidence and mortality in rabbits. Our results indicate that andrographolide inhibits cellular arrhythmias (delayed afterdepolarizations and triggered activities) and aconitine-induced arrhythmias , and these effects result from I and I inhibition. Andrographolide may be useful as a class I and IV antiarrhythmic therapeutic.
穿心莲内酯对心血管系统具有保护作用。为研究其心脏电生理效应,采用全细胞膜片钳和电流钳技术记录动作电位以及电压门控钠(I)、钙(I)和钾(I、I、I和I)电流。此外,在心电图上评估穿心莲内酯对乌头碱诱导的心律失常的影响。我们发现,穿心莲内酯缩短了兔左心室和左心房肌细胞的动作电位时程,并降低了最大除极速度。穿心莲内酯减弱了动作电位时程的频率依赖性,并减少或消除了左心室肌细胞中由异丙肾上腺素(1μM)和高钙([Ca]=3.6 mM)诱导的延迟后去极化和触发活动。穿心莲内酯还浓度依赖性地抑制I和I,但对兔左心室和左心房肌细胞中的I、I、I或I没有影响。穿心莲内酯治疗增加了乌头碱诱导的心律失常的时间和剂量阈值,并降低了兔心律失常的发生率和死亡率。我们的结果表明,穿心莲内酯抑制细胞性心律失常(延迟后去极化和触发活动)以及乌头碱诱导的心律失常,这些作用源于对I和I的抑制。穿心莲内酯可能作为I类和IV类抗心律失常治疗药物有用。