ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2015
Effects of L-type calcium channel and human ether-a-go-go related gene blockers on the electrical activity of the human heart: a simulation study.
Article in Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 28 citations in OpenAlex.
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- MRI-Based Computational Torso/Biventricular Multiscale Models to Investigate the Impact of Anatomical Variability on the ECG QRS Complex.Frontiers in physiology · 2019Article
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- Human ventricular activation sequence and the simulation of the electrocardiographic QRS complex and its variability in healthy and intraventricular block conditions.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2016Article
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Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsClass III and IV drugs affect cardiac human ether-a-go-go related gene (IKr) and L-type calcium (ICaL) channels, resulting in complex alterations in repolarization with both anti- and pro-arrhythmic consequences. Interpretation of their effects on cellular and electrocardiogram (ECG)-based biomarkers for risk stratification is challenging. As pharmaceutical compounds often exhibit multiple ion channel effects, our goal is to investigate the simultaneous effect of ICaL and IKr block on human ventricular electrophysiology from ionic to ECG level. METHODS AND
resultsSimulations are conducted using a human body torso bidomain model, which includes realistic representation of human membrane kinetics, anatomy, and fibre orientation. A simple block pore model is incorporated to simulate drug-induced ICaL and IKr blocks, for drug dose = 0, IC50, 2× IC50, 10× IC50, and 30× IC50. Drug effects on human ventricular activity are quantified for different degrees and combinations of ICaL and IKr blocks from the ionic to the body surface ECG level. Electrocardiogram simulations show that ICaL block results in shortening of the QT interval, ST elevation, and reduced T-wave amplitude, caused by reduction in action potential duration and action potential amplitude during the plateau phase, and in repolarization times. In contrast, IKr block results in QT prolongation and reduced T-wave amplitude. When ICaL and IKr blocks are combined, the degree of ICaL block strongly determines QT interval whereas the effect of IKr block is more pronounced on the T-wave amplitude.
conclusionOur simulation study provides new insights into the combined effect of ICaL and IKr blocks on human ventricular activity using a multiscale computational human torso model.
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