ArticleJournal of pharmacological and toxicological methods2017
Computational modeling for cardiac safety pharmacology analysis: Contribution of fibroblasts.
Article in Journal of pharmacological and toxicological methods, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 9 citations in OpenAlex.
- Papillary Muscles of the Left Ventricle: Integrating Electrical and Mechanical Dynamics.Journal of cardiovascular development and disease · 2024Review
- Nonmyocytes as electrophysiological contributors to cardiac excitation and conduction.American journal of physiology. Heart and circulatory physiology · 2023Review
- Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges.Frontiers in physiology · 2018Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
introductionDrug-induced proarrhythmic potential is an important regulatory criterion in safety pharmacology. The application of in silico approaches to predict proarrhythmic potential of new compounds is under consideration as part of future guidelines. Current approaches simulate the electrophysiology of a single human adult ventricular cardiomyocyte. However, drug-induced proarrhythmic potential can be different when cardiomyocytes are surrounded by non-muscle cells. Incorporating fibroblasts in models of myocardium is important particularly for predicting a drugs cardiac liability in the aging population - a growing population who take more medications and exhibit increased cardiac fibrosis. In this study, we used computational models to investigate the effects of fibroblast coupling on the electrophysiology and response to drugs of cardiomyocytes.
methodsA computational model of cardiomyocyte electrophysiology and ion handling (O'Hara, Virag, Varro, & Rudy, 2011) is coupled to a passive model of fibroblast electrophysiology to test the effects of three compounds that block cardiomyocyte ion channels. Results are compared to model results without fibroblast coupling to see how fibroblasts affect cardiomyocyte action potential duration at 90% repolarization (APD
resultsSimulation results show changes in cardiomyocyte APD DISCUSSION: Coupling cardiomyocytes and fibroblasts are predicted to decrease proarrhythmic susceptibility under dofetilide, vardenafil and nebivolol block. However, this result is sensitive to parameters which define the electrophysiological function of the fibroblast. Fibroblast membrane capacitance and conductance (C
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Registered trials
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