Key result
Combination therapy of chloroquine and azithromycin significantly increased field potential duration and decreased beat period and spike slope in human embryonic stem cell-derived cardiomyocytes compared to chloroquine alone.
Why the study?
Co-administration of chloroquine and azithromycin in COVID-19 trials caused severe side effects, including cardiac arrhythmia, but the mechanisms of induced cardiotoxicity required electrophysiological evaluation.
Does the combination of chloroquine and azithromycin increase cardiotoxicity compared to chloroquine monotherapy in human embryonic stem cell-derived cardiomyocytes?
Does the combination of chloroquine and azithromycin increase cardiotoxicity compared to chloroquine monotherapy in human embryonic stem cell-derived cardiomyocytes?
Azithromycin reinforces the cardiotoxicity (prolonged field potential duration) induced by chloroquine in human embryonic stem cell-derived cardiomyocytes, supporting clinical observations of arrhythmias.
Suggests azithromycin may potentiate chloroquine cardiotoxicity in vitro; hypothesis-generating and should not yet change practice.
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 cellderived 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. [BMB Reports 2020; 53(10): 545-550].
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Kim et al. (2020) studied Cardiotoxicity. Chloroquine and Azithromycin vs. Control vehicle (DMSO) or Chloroquine monotherapy was evaluated on Electrophysiological properties (Field potential duration, beat period, spike slope). Combination therapy of chloroquine and azithromycin significantly increased field potential duration and decreased beat period and spike slope in human embryonic stem cell-derived cardiomyocytes compared to chloroquine alone.
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