Analysis of the response of human iPSC-derived cardiomyocyte tissue to ICaL block. A combined in vitro and in silico approach

The high incidence of cardiac arrythmias underlines the need for assessment pharmacological therapies. In this field drug efficacy, as in safety highlighted by Comprehensive Vitro Proarrhythmia Assay initiative, new pillars research have become crucial: firstly, integration in-silico experiments, and secondly evaluation fully integrated biological systems, such human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). study, we therefore aimed to combine in-vitro experiments simulations evaluate antiarrhythmic effect L-type calcium current (ICaL) block hiPSC-CMs. For this, hiPSC-CM preparations were cultured an equivalent virtual tissue was modeled. Re-entry patterns electrical activation several biomarkers obtained before after ICaL block. also reproduced using a composed adult ventricular (hAdultV-CMs). analysis phases, currents factor propagation showed increased size re-entry core when blocked result depressed cellular excitability. bigger wavefront curvature yielded reductions 12.2%, 6.9%, 4.2% frequency cultures, hiPSC-CM, hAdultV-CM tissues, respectively. Furthermore, led 47.8% shortening vulnerable window vanishment tissue. consistent behavior between hiPSC-CMs hAdultV-CMs evidences that tissues are suitable assessing done present study through