Jeong Hyung Ki, Yoon Namsik, Kim Yoo Ri, Lee Ki Hong, Park Hyung Wook
Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Korea.
Institute of Wonkang Medical Science, Iksan, Korea.
J Korean Med Sci. 2025 Jan 6;40(1):e2. doi: 10.3346/jkms.2025.40.e2.
The ionic mechanism underlying Brugada syndrome (BrS) arises from an imbalance in transient outward current flow between the epicardium and endocardium. Previous studies report that artemisinin, originally derived from a Chinese herb for antimalarial use, inhibits the Ito current in canines. In a prior study, we showed the antiarrhythmic effects of artemisinin in BrS wedge preparation models. However, quinidine remains a well-established antiarrhythmic agent for treating BrS. Therefore, this study aims to investigate the efficacy of combining artemisinin with low-dose quinidine in suppressing ventricular tachyarrhythmia (VTA) in experimental canine BrS models.
Transmural pseudo-electrocardiogram and epicardial/endocardial action potential (AP) were recorded from coronary-perfused canine right ventricular wedge preparation. To mimic the BrS model, acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and Ito agonist NS5806 (6-10 μM) were administered until VTA was induced. Subsequently, low-dose quinidine (1-2 μM) combined with artemisinin (100 μM) was perfused to mitigate VTA. Key parameters, including AP duration, J wave area, notch index, and T wave dispersion, were measured.
After administering the provocation agents, all sample models exhibited prominent J waves and VTA. Artemisinin alone (100-150 μM) suppressed VTA and restored the AP dome in all three preparations. Its infusion resulted in reductions in the J wave area and epicardial notch index. Consequently, low-dose quinidine (1-2 μM) did not fully restore the AP dome in all six sample models. However, when combined with additional artemisinin (100 μM), low-dose quinidine effectively suppressed VTA in all six models and restored the AP dome while also decreasing the J wave area and epicardial notch index.
Low-dose quinidine alone fails to fully alleviate VTA in the BrS wedge model. However, its combination with artemisinin effectively suppresses VTA. Artemisinin may reduce the therapeutic dose of quinidine, potentially minimizing its associated adverse effects.
Brugada综合征（BrS）潜在的离子机制源于心外膜和心内膜之间瞬时外向电流的不平衡。先前的研究报道，最初源自一种用于抗疟疾的中国草药的青蒿素，可抑制犬类的Ito电流。在之前的一项研究中，我们展示了青蒿素在BrS楔形制备模型中的抗心律失常作用。然而，奎尼丁仍然是治疗BrS的一种成熟的抗心律失常药物。因此，本研究旨在探讨青蒿素与低剂量奎尼丁联合应用在实验性犬BrS模型中抑制室性快速心律失常（VTA）的疗效。
从冠状动脉灌注的犬右心室楔形制备物中记录跨壁伪心电图和心外膜/心内膜动作电位（AP）。为模拟BrS模型，给予乙酰胆碱（3 μM）、钙通道阻滞剂维拉帕米（1 μM）和Ito激动剂NS5806（6 - 10 μM），直至诱发VTA。随后，灌注低剂量奎尼丁（1 - 2 μM）与青蒿素（100 μM）联合应用以减轻VTA。测量包括AP持续时间、J波面积、切迹指数和T波离散度等关键参数。
给予激发剂后，所有样本模型均表现出明显的J波和VTA。单独使用青蒿素（100 - 150 μM）可抑制VTA并恢复所有三种制备物中的AP圆顶。其输注导致J波面积和心外膜切迹指数降低。因此，低剂量奎尼丁（1 - 2 μM）未能在所有六个样本模型中完全恢复AP圆顶。然而，当与额外的青蒿素（100 μM）联合使用时，低剂量奎尼丁在所有六个模型中均有效抑制VTA并恢复AP圆顶，同时还降低了J波面积和心外膜切迹指数。
单独使用低剂量奎尼丁不能完全缓解BrS楔形模型中的VTA。然而，其与青蒿素联合应用可有效抑制VTA。青蒿素可能会降低奎尼丁的治疗剂量，从而可能将其相关不良反应降至最低。
