Artemisinin combined with low dose quinidine suppresses ventricular tachyarrhythmia in a model of Brugada syndrome

Abstract

Abstract Background The mechanism of Brugada syndrome (BrS) is unclear. One of the mechanisms has been suggested that uneven dispersion of Ito channel between epicardium and endocardium induced ventricular arrhythmia. Artemisinin, which originates from a Chinese herb and is used widely as an antimalarial drug, is reported to inhibit the Ito channel in a canine experimental model previously. Objective We aimed to investigate the effect of artemisinin, alone and in combination with low dose quinidine, on the suppression of ventricular tachyarrhythmia in BrS in a canine experimental model. Methods We recorded transmural pseudo-ECG and epicardial/endocardial action potentials (APs) from coronary-perfused canine right ventricular wedge preparation. We used acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and Ito agonist NS5806 (6 – 10 μM) to mimic the BrS model. We induced ventricular arrhythmia and then perfused low dose quinidine (1 – 2 μM) alone and additionally perfused artemisinin (100 – 150 μM) to suppress the arrhythmia. We evaluated ventricular arrhythmia inducibility and measured AP duration, J wave area, notch index, and T wave dispersion. Results The provocation agents induced prominent J wave in all sample models. In 6 sample models out of 8 for artemisinin alone group, ventricular arrhythmia was induced. Artemisinin suppressed ventricular arrhythmia and recovered the AP dome in all preparations. J wave area and epicardial notch index were also decreased after artemisinin perfusion. The low dose quinidine (1 – 2 μM) did not completely suppressed the ventricular arrhythmia in 6 out of 6 sample models. However, additional artemisinin (100 – 200 μM) infusion suppressed the ventricular arrhythmia in all sample models and restored the AP dome. J wave area and epicardial notch index were also decreased. Conclusions Our findings suggest that artemisinin can alleviate ventricular arrhythmia in the BrS wedge preparation model. Combining artemisinin with low dose quinidine may further suppress ventricular arrhythmia by inhibiting potassium channels, including Ito channel. Artemisinin might reduce the therapeutic dose of quinidine by additional inhibition of potassium channels.