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Cardiotoxicity induced by combination therapy of chloroquine and azithromycin in human embryonic stem cell-derived cardiomyocytes
Ye Seul Kim1,# (Graduate student), Soo Yong Lee2,# (Professor), Jung Won Yoon1 (Graduate student), Dasol Kim1 (Graduate student), Sangbin Yu1 (Graduate student), Jeong Su Kim2 (Professor), Jae Ho Kim 1,* (Professor)
1Department of Physiology, Pusan National University College of Medicine,
2Division of Cardiology, Pusan National University Yangsan Hospital
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 co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To clarify the cardiotoxicity induced by CQ and AZM, in this study, we examined the effects of these drugs 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 beating period and spike slope of hESC-CMs as compared to 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.
Abstract, Accepted Manuscript(in press) [Submitted on August 9, 2020, Accepted on August 26, 2020]
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