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KMID : 0368120230530040239
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Korean Circulation Journal
2023 Volume.53 No. 4 p.239 ~ p.250
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Antiarrhythmic Effect of Artemisinin in an Ex-vivo Model of Brugada Syndrome Induced by NS5806
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Jeong Hyung-Ki
Hong Seo-Na
Yoon Nam-Sik
Lee Ki-Hong
Park Hyung-Wook
Cho Jeong-Gwan
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Abstract
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Background and Objectives: 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 (Ito) 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 Ito channels, has been previously reported. We investigated the effect of artemisinin on the suppression of electrocardiographic manifestations in a canine experimental model of BrS.
Methods: 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 Ito agonist NS5806 (6?10?μM) were used. Artemisinin (100?150 μM) was then perfused to ameliorate the ventricular tachyarrhythmia in the BrS models.
Results: 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.
Conclusions: Our findings suggest that artemisinin has an antiarrhythmic effect on wedge preparation models of BrS. It might work by inhibition of potassium channels including Ito channels, subsequently suppressing ventricular tachycardia/ventricular fibrillation.
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KEYWORD
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Brugada syndrome, Sudden cardiac death, Anti-arrhythmia agents
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