Jeong Hyung Ki, Hong Seo Na, Yoon Namsik, Lee Ki Hong, Park Hyung Wook, Cho Jeong Gwan
Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Korea.
Department of Cardiology, Kwangju Christian Hospital, Gwangju, Korea.
Korean Circ J. 2023 Apr;53(4):239-250. doi: 10.4070/kcj.2022.0312.
Brugada syndrome (BrS) is an inherited arrhythmia syndrome that presents as sudden cardiac death (SCD) without structural heart disease. One of the mechanisms of SCD has been suggested to be related to the uneven dispersion of transient outward potassium current () channels between the epicardium and endocardium, thus inducing ventricular tachyarrhythmia. Artemisinin is widely used as an antimalarial drug. Its antiarrhythmic effect, which includes suppression of channels, has been previously reported. We investigated the effect of artemisinin on the suppression of electrocardiographic manifestations in a canine experimental model of BrS.
Transmural pseudo-electrocardiograms and epicardial/endocardial transmembrane action potentials (APs) were recorded from coronary-perfused canine right ventricular wedge preparations (n=8). To mimic the BrS phenotypes, acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and agonist NS5806 (6-10 μM) were used. Artemisinin (100-150 μM) was then perfused to ameliorate the ventricular tachyarrhythmia in the BrS models.
The provocation agents induced prominent J waves in all the models on the pseudo-electrocardiograms. The epicardial AP dome was attenuated. Ventricular tachyarrhythmia was induced in six out of 8 preparations. Artemisinin suppressed ventricular tachyarrhythmia in all 6 of these preparations and recovered the AP dome of the right ventricular epicardium in all preparations (n=8). J wave areas and epicardial notch indexes were also significantly decreased after artemisinin perfusion.
Our findings suggest that artemisinin has an antiarrhythmic effect on wedge preparation models of BrS. It might work by inhibition of potassium channels including channels, subsequently suppressing ventricular tachycardia/ventricular fibrillation.
Brugada综合征（BrS）是一种遗传性心律失常综合征，表现为无结构性心脏病的心脏性猝死（SCD）。SCD的机制之一被认为与瞬时外向钾电流（）通道在心外膜和心内膜之间的不均匀分布有关，从而诱发室性快速心律失常。青蒿素被广泛用作抗疟药物。此前已有报道称其具有抗心律失常作用，包括对通道的抑制作用。我们研究了青蒿素对BrS犬实验模型中心电图表现的抑制作用。
从冠状动脉灌注的犬右心室楔形标本（n = 8）记录跨壁伪心电图和心外膜/心内膜跨膜动作电位（APs）。为模拟BrS表型，使用了乙酰胆碱（3 μM）、钙通道阻滞剂维拉帕米（1 μM）和激动剂NS5806（6 - 10 μM）。然后灌注青蒿素（100 - 150 μM）以改善BrS模型中的室性快速心律失常。
在所有模型的伪心电图上，激发剂均诱发了明显的J波。心外膜AP波峰减弱。8个标本中有6个诱发了室性快速心律失常。青蒿素抑制了所有这6个标本中的室性快速心律失常，并使所有标本（n = 8）右心室心外膜的AP波峰恢复。青蒿素灌注后，J波面积和心外膜切迹指数也显著降低。
我们的研究结果表明，青蒿素对BrS楔形标本模型具有抗心律失常作用。它可能通过抑制包括通道在内的钾通道起作用，随后抑制室性心动过速/心室颤动。
