How drugs modulate the performance of the human heart

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dc.catalogadorgjm
dc.contributor.authorPeirlinck, M.
dc.contributor.authorYao, J.
dc.contributor.authorSahli Costabal, Francisco
dc.contributor.authorKuhl, E.
dc.date.accessioned2024-05-30T16:23:25Z
dc.date.available2024-05-30T16:23:25Z
dc.date.issued2022
dc.description.abstractMany 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 % 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.
dc.fuente.origenORCID
dc.identifier.doi10.1007/s00466-022-02146-1
dc.identifier.urihttps://doi.org/10.1007/s00466-022-02146-1
dc.identifier.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-85125717485&partnerID=MN8TOARS
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86076
dc.information.autorucEscuela de Ingeniería; Sahli Costabal, Francisco; S/I; 154857
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final1411
dc.pagina.inicio1397
dc.revistaComputational Mechanics
dc.rightsacceso restringido
dc.subjectCardiac mechanics
dc.subjectCardiac electrophysiology
dc.subjectDrug-induced arrhythmia
dc.subjectComputational whole-heart modeling
dc.subjectElectro-mechanical coupling
dc.subjectHemodynamic coupling
dc.subject.ddc600
dc.subject.deweyTecnologíaes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHow drugs modulate the performance of the human heart
dc.typeartículo
dc.volumen69
sipa.codpersvinculados154857
sipa.trazabilidadORCID;2024-05-27
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