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http://dx.doi.org/10.5483/BMBRep.2020.53.10.165

Cardiotoxicity induced by the combination therapy of chloroquine and azithromycin in human embryonic stem cell-derived cardiomyocytes  

Kim, Ye Seul (Department of Physiology, School of Medicine, Pusan National University)
Lee, Soo Yong (Division of Cardiology, Department of Internal Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine)
Yoon, Jung Won (Department of Physiology, School of Medicine, Pusan National University)
Kim, Dasol (Department of Physiology, School of Medicine, Pusan National University)
Yu, Sangbin (Department of Physiology, School of Medicine, Pusan National University)
Kim, Jeong Su (Division of Cardiology, Department of Internal Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine)
Kim, Jae Ho (Department of Physiology, School of Medicine, Pusan National University)
Publication Information
BMB Reports / v.53, no.10, 2020 , pp. 545-550 More about this Journal
Abstract
Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs.
Keywords
Cardiomyocytes; Cardiotoxicity; Chloroquine; COVID-19; Embryonic stem cells;
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