Aconitine‑induced cardiac arrhythmia in human induced pluripotent stem cell‑derived cardiomyocytes

Zhang,Feng; Cai,Lin; Zhang,Jing; Qi,Xueyan; Lu,Chengzhi

doi:10.3892/etm.2018.6644

Aconitine‑induced cardiac arrhythmia in human induced pluripotent stem cell‑derived cardiomyocytes

Authors:
- Feng Zhang
- Lin Cai
- Jing Zhang
- Xueyan Qi
- Chengzhi Lu
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Affiliations: Department of Cardiology, Tianjin First Central Hospital, Tianjin 300192, P.R. China, Department of Cardiology, Tianjin International Medical Center, Tianjin First Central Hospital, Tianjin 300192, P.R. China
Published online on: August 22, 2018 https://doi.org/10.3892/etm.2018.6644
Pages: 3497-3503
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pre‑clinical evaluation of cardiac dysfunction is important for assessing the safety of traditional or novel medicines due to the universality of potential drug‑induced heart failure and irreversible arrhythmia. Aconitine (ACO), a traditionally used anti‑pyretic, analgesic and anti‑rheumatic drug, has been reported to have arrhythmogenic effects. In the present study, the Real‑Time Cellular Analysis Cardio system was applied to evaluate the arrhythmogenic effects of ACO in human induced pluripotent stem cell‑derived cardiomyocytes (hiPSC‑CMs). The results indicated that ACO is capable of increasing the frequency and decreasing the amplitude of hiPSC‑CM contraction in a dose‑ and time‑dependent manner. ACO at 0.25 µM increased the beating rate of hiPSC‑CMs by 3.7‑fold within 30 min, while 3.0 µM of ACO increased the beating rate by 7.3‑fold. The present study also evaluated the potential pro‑apoptotic effects of ACO by using caspase‑3 and caspase‑9 kits. To the best of our knowledge, the present study was the first to record the ACO‑induced cardiac arrhythmia of hiPSC‑CMsin real‑time. The results also indicate that ACO‑induced cell death is mediated, at least in part, by caspase‑dependent apoptotic pathways.

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