ArticleToxicological sciences : an official journal of the Society of Toxicology2021
Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
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- Quantitative assessment of the usability of electromechanical human-based modelling and simulation to replace Langendorff isolated rabbit heart experiments in the preclinical setting.Frontiers in pharmacology · 2025Article
- Modeling drug-induced mitochondrial toxicity with human primary cardiomyocytes.Science China. Life sciences · 2024Article
- Major adverse cardiovascular events (MACE) in patients with severe COVID-19 registered in the ISARIC WHO clinical characterization protocol: A prospective, multinational, observational study.Journal of critical care · 2023Observational
- Using the Correlation Intensity Index to Build a Model of Cardiotoxicity of Piperidine Derivatives.Molecules (Basel, Switzerland) · 2023Article
- Hydroxychloroquine and azithromycin alter the contractility of living porcine heart slices.Frontiers in pharmacology · 2023Article
- Article
- Anti-malarial drugs: Mechanisms underlying their proarrhythmic effects.British journal of pharmacology · 2022Review
- Toxicology evaluation of overdose hydroxychloroquine on zebrafish (Danio rerio) embryos.Scientific reports · 2022Article
- Spike-based adenovirus vectored COVID-19 vaccine does not aggravate heart damage after ischemic injury in mice.Communications biology · 2022Article
- Functional isolation, culture and cryopreservation of adult human primary cardiomyocytes.Signal transduction and targeted therapy · 2022Article
- Hydroxychloroquine Blood Concentrations Can Be Clinically Relevant Also After Drug Discontinuation.Drugs in R&D · 2022Article
- In vitro ion channel profile and ex vivo cardiac electrophysiology properties of the R(-) and S(+) enantiomers of hydroxychloroquine.European journal of pharmacology · 2022Article
- Open-access database of literature derived drug-related Torsade de Pointes cases.BMC pharmacology & toxicology · 2022Article
- Rapid Onset and Resolution of Hydroxychloroquine Cardiomyopathy: A Case Report.Case reports in rheumatology · 2022Article
- Local Anesthetic Like Inhibition of the Cardiac NaJournal of experimental pharmacology · 2022Article
- Assessment of proarrhythmogenic risk for chloroquine and hydroxychloroquine using the CiPA concept.European journal of pharmacology · 2021Article
- Characterization of the molecular mechanisms underlying azithromycin-induced cardiotoxicity using human-induced pluripotent stem cell-derived cardiomyocytes.Clinical and translational medicine · 2021Article
- Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies.Diabetology & metabolic syndrome · 2021Article
- Arrhythmogenic and antiarrhythmic actions of late sustained sodium current in the adult human heart.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substantial efforts have been recently committed to develop coronavirus disease-2019 (COVID-19) medications, and Hydroxychloroquine alone or in combination with Azithromycin has been promoted as a repurposed treatment. Although these drugs may increase cardiac toxicity risk, cardiomyocyte mechanisms underlying this risk remain poorly understood in humans. Therefore, we evaluated the proarrhythmia risk and inotropic effects of these drugs in the cardiomyocyte contractility-based model of the human heart. We found Hydroxychloroquine to have a low proarrhythmia risk, whereas Chloroquine and Azithromycin were associated with high risk. Hydroxychloroquine proarrhythmia risk changed to high with low level of K+, whereas high level of Mg2+ protected against proarrhythmic effect of high Hydroxychloroquine concentrations. Moreover, therapeutic concentration of Hydroxychloroquine caused no enhancement of elevated temperature-induced proarrhythmia. Polytherapy of Hydroxychloroquine plus Azithromycin and sequential application of these drugs were also found to influence proarrhythmia risk categorization. Hydroxychloroquine proarrhythmia risk changed to high when combined with Azithromycin at therapeutic concentration. However, Hydroxychloroquine at therapeutic concentration impacted the cardiac safety profile of Azithromycin and its proarrhythmia risk only at concentrations above therapeutic level. We also report that Hydroxychloroquine and Chloroquine, but not Azithromycin, decreased contractility while exhibiting multi-ion channel block features, and Hydroxychloroquine's contractility effect was abolished by Azithromycin. Thus, this study has the potential to inform clinical studies evaluating repurposed therapies, including those in the COVID-19 context. Additionally, it demonstrates the translational value of the human cardiomyocyte contractility-based model as a key early discovery path to inform decisions on novel therapies for COVID-19, malaria, and inflammatory diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.