The cardiac electrophysiology effects of higenamine in guinea pig heart
The cardiac electrophysiology effects of higenamine in guinea pig heart
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去甲乌药碱对豚鼠心脏电生理的影响
DOI：
10.1016/j.biopha.2018.10.022
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发表时间：
2019-01-01
影响因子：
7.5
通讯作者：
Jiang, Jiandong
中科院分区：
文献类型：
--
作者：
Wang, Yuhong;Geng, Jing;Jiang, Jiandong
背景：去甲乌药碱（HG）是从板蓝根中提取的具有强心作用的活性化合物。由于其作为强有力的心脏变力和变时剂的作用，已被中国SFDA批准用于临床试验。然而，HG对心脏电生理的直接作用方式尚不清楚。方法：在细胞水平和离体器官水平进行实验。用膜片钳技术测定豚鼠左心室肌细胞主要离子电流和动作电位时程。结果：在离体豚鼠心肌细胞中，HG以浓度依赖性和电压依赖性方式增加ICa-L和I-Ks。它同时增强ICa-L和I-Ks，用于同步化。ICa-L和I（Ks）的EC_（50）值分别为0.27 μ M和0.64 μ M。HG（0.1 μ M、0.5 μ M和1 μ M）对I-Kr和I-Na无影响。HG在低浓度时稍延长APD，在高浓度时缩短APD。HG可引起延迟后除极（DAD），表现出一定的保护作用。在离体灌流心脏中，HG通过作用于窦房结细胞而增加心率，但即使在高浓度下也不诱导心律失常。控制心率的窦房结的EC（50）值为0.13 μ M。窦房结细胞比心室肌细胞对HG更敏感。HG对心室肌细胞和窦房结细胞的作用均是通过刺激β 1-AR介导的。结论：HG对窦房结细胞的作用具有优势。HG似乎通过其对窦房结细胞的主导作用来控制心脏电生理，而不诱导引起心律失常的异位活动。因此，HG可能对治疗心动过缓有用。
Background: Higenamine (HG) is an active compound derived from Aconiti root with a cardiotonic effect. It has been approved by the Chinese SFDA for clinical trials due to its effect as a potent inotropic and chronotropic agent in the heart. However, the direct mode of action of HG on cardiac electrophysiology is unclear.Methods: The experiments were performed at both cell levels and the isolated organ. The major cardiac ion currents and the action potential duration (APD) were measured using patch-clamps in single guinea-pig left ventricular myocytes. ECG was recorded in isolated guinea pig hearts.Results: In the left ventricular myocytes, HG increased ICa-L and I-Ks in concentration- and voltage-dependent manners in the left ventricular myocytes. It potentiated the ICa-L and I-Ks, simultaneously for synchronization. The EC50 values were 0.27 mu M and 0.64 mu M for the ICa-L and I(Ks )respectively. HG (0.1 mu M, 0.5 mu M and 1 mu M) had no effect on the I-Kr and I-Na . HG slightly prolonged APD at lower concentrations, and shortened the APD at higher concentrations. HG can induce the delayed after depolarization (DAD), which showed some pro-arrhythmic effect. In the isolated perfused heart, HG increased the heart rate via an action on the sinoatrial node cells, but did not induce cardiac arrhythmias, even at high concentrations. The EC(50 )value for the sinoatrial node that controls the heart rate was 0.13 mu M. The sinoatrial node cells appeared to be more sensitive than ventricular myocytes to HG. The effects of HG on ventricular cells and sinoatrial node cells were both mediated through stimulation of beta 1-AR.Conclusion: We show for the first time that HG produced a predominant action on the sinoatrial node. HG appears to control the cardiac electrophysiology through its predominant effect on the sinoarial node cells, without induction of the ectopic activity that causes cardiac arrhythmias. Thus, HG might be useful for the treatment of bradycardia.