How drugs modulate the performance of the human heart

Journal Article (2022)
Author(s)

M. Peirlinck (Stanford University, TU Delft - Medical Instruments & Bio-Inspired Technology)

J Yao (Dassault Systèmes Simulia Corporation)

Francisco Sahli Costabal (Pontificia Universidad Católica de Chile)

Ellen Kuhl (Stanford University)

Research Group
Medical Instruments & Bio-Inspired Technology
Copyright
© 2022 M. Peirlinck, J. Yao, F. Sahli Costabal, E. Kuhl
DOI related publication
https://doi.org/10.1007/s00466-022-02146-1
More Info
expand_more
Publication Year
2022
Language
English
Copyright
© 2022 M. Peirlinck, J. Yao, F. Sahli Costabal, E. Kuhl
Research Group
Medical Instruments & Bio-Inspired Technology
Issue number
6
Volume number
69
Pages (from-to)
1397-1411
Reuse Rights

Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.

Abstract

Many drugs interact with ion channels in the cells of our heart and trigger heart rhythm disorders with potentially fatal consequences. Computational modeling can provide mechanistic insight into the onset and propagation of drug-induced arrhythmias, but the effect of drugs on the mechanical performance of the heart remains poorly understood. Here we establish a multiphysics framework that integrates the biochemical, electrical, and mechanical effects of drugs, from cellular excitation to cardiac contraction. For the example of the drug dofetilide, we show that drug concentrations of 5x and 8x increase the heart rate to 122 and 114 beats per minute, increase myofiber stretches by 5%, and decrease overall tissue relaxation by 6%. This results in inter-ventricular and atrial-ventricular dyssynchronies and changes in cardiac output by - 2.5 % and +7%. Our results emphasize the need for multiphysics modeling to better understand the mechanical implications of drug-induced arrhythmias. Knowing how different drug concentrations affect the performance of the heart has important clinical implications in drug safety evaluation and personalized medicine.

Files

Peirlinck2022_Article_HowDrugs... (pdf)
(pdf | 2.65 Mb)
- Embargo expired in 07-09-2022
License info not available