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| Content Provider | IEEE Xplore Digital Library |
|---|---|
| Author | Paci, M. Hyttinen, J. Severi, S. |
| Copyright Year | 2013 |
| Description | Author affiliation: ELT, Tampere Univ. of Technol., Tampere, Finland (Paci, M.; Hyttinen, J.) || DEI, Univ. of Bologna, Bologna, Italy (Severi, S.) |
| Abstract | The production of disease-specific lines of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) opened new opportunities to study genetic cardiac disorders such as Long QT (LQT) syndrome. We focused on the computational modelling of hiPSC-CMs with LQT1 syndrome which reduces the slow delayed rectifYing, hs, current. Both control and LQT1 hs formulations are based on recently published hs data, which were integrated into our previous model of hiPSC-CM action potential (AP). The control model reproduced the automaticity and the shape of the experimental spontaneous APs. In simulations, LQT1 mutation induced a marked prolongation of the action potential duration $(APD_{90}$ + 27.5%). By simulating the application of isoproterenol in the LQT 1 model, the mutation effects were exacerbated $(APD_{90}$ further increased by 23.5%) due to the impaired rate adaptation, as shown by the 11.8% increment of the ratio AP $D_{90}/Cycle$ Length. Our in-silico analysis confirmed that in hiPSC-CMs hs plays a more important role in AP repolarization than in adult cardiomyocytes. Our model explains this behavior by a reduced repolarization reserve. This is manifested by the fact that hr and hI were reduced compared to the adult AP in order to reproduce the control hiPSC-CMs AP shape. |
| Sponsorship | IEEE Eng. Med. Biol. Soc. |
| Starting Page | 1239 |
| Ending Page | 1242 |
| File Size | 644075 |
| Page Count | 4 |
| File Format | |
| ISBN | 9781479908844 |
| ISSN | 2325887X |
| e-ISBN | 9781479908868 |
| Language | English |
| Publisher | Institute of Electrical and Electronics Engineers, Inc. (IEEE) |
| Publisher Date | 2013-09-22 |
| Publisher Place | Spain |
| Access Restriction | Subscribed |
| Rights Holder | Creative Commons Attribution License 2.5 (CCAL) |
| Subject Keyword | Abstracts Medical treatment Biological system modeling Computational modeling |
| Content Type | Text |
| Resource Type | Article |
| Subject | Computer Science Cardiology and Cardiovascular Medicine |
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