ArticleScience advances2015
Screening system for drug-induced arrhythmogenic risk combining a patch clamp and heart simulator.
Article in Science advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Towards chamber specific heart-on-a-chip for drug testing applications.Advanced drug delivery reviews · 2020Pooled it
- Machine learning approach to evaluate TdP risk of drugs using cardiac electrophysiological model including inter-individual variability.Frontiers in physiology · 2023Article
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- Tunable electroconductive decellularized extracellular matrix hydrogels for engineering human cardiac microphysiological systems.Biomaterials · 2021Article
- Chloroquine and hydroxychloroquine provoke arrhythmias at concentrations higher than those clinically used to treat COVID-19: A simulation study.Clinical and translational science · 2021Article
- Integrated Isogenic Human Induced Pluripotent Stem Cell-Based Liver and Heart Microphysiological Systems Predict Unsafe Drug-Drug Interaction.Frontiers in pharmacology · 2021Article
- Sex Differences in Drug-Induced Arrhythmogenesis.Frontiers in physiology · 2021Article
- Ionic mechanisms of ST segment elevation in electrocardiogram during acute myocardial infarction.The journal of physiological sciences : JPS · 2020Article
- Review
- Classifying Drugs by their Arrhythmogenic Risk Using Machine Learning.Biophysical journal · 2020Article
- Identification of Drug-Induced Multichannel Block and Proarrhythmic Risk in Humans Using Continuous T Vector Velocity Effect Profiles Derived From Surface Electrocardiograms.Frontiers in physiology · 2020Article
- General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy.Clinical pharmacology and therapeutics · 2020Article
- Clinical and pharmacological application of multiscale multiphysics heart simulator, UT-Heart.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Review
- Predicting critical drug concentrations and torsadogenic risk using a multiscale exposure-response simulator.Progress in biophysics and molecular biology · 2019Article
- Quantitative Systems Pharmacology Models for a New International Cardiac Safety Regulatory Paradigm: An Overview of the Comprehensive In Vitro Proarrhythmia Assay In Silico Modeling Approach.CPT: pharmacometrics & systems pharmacology · 2019Review
- Assessment of an In Silico Mechanistic Model for Proarrhythmia Risk Prediction Under the CiPA Initiative.Clinical pharmacology and therapeutics · 2019Article
- Global Sensitivity Analysis of Ventricular Myocyte Model-Derived Metrics for Proarrhythmic Risk Assessment.Frontiers in pharmacology · 2019Article
- Arrhythmic hazard map for a 3D whole-ventricle model under multiple ion channel block.British journal of pharmacology · 2018Article
- Towards Bridging Translational Gap in Cardiotoxicity Prediction: an Application of Progressive Cardiac Risk Assessment Strategy in TdP Risk Assessment of Moxifloxacin.The AAPS journal · 2018Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To save time and cost for drug discovery, a paradigm shift in cardiotoxicity testing is required. We introduce a novel screening system for drug-induced arrhythmogenic risk that combines in vitro pharmacological assays and a multiscale heart simulator. For 12 drugs reported to have varying cardiotoxicity risks, dose-inhibition curves were determined for six ion channels using automated patch clamp systems. By manipulating the channel models implemented in a heart simulator consisting of more than 20 million myocyte models, we simulated a standard electrocardiogram (ECG) under various doses of drugs. When the drug concentrations were increased from therapeutic levels, each drug induced a concentration-dependent characteristic type of ventricular arrhythmia, whereas no arrhythmias were observed at any dose with drugs known to be safe. We have shown that our system combining in vitro and in silico technologies can predict drug-induced arrhythmogenic risk reliably and efficiently.
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Registered trials
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.