Adaptation of the Calcium-dependent Tension Development in Ventricular Cardiomyocytes
Today a variety of models describe the physiological behavior of the heart on a cellular level. The intracellular calcium concentration plays an important role, since it is the main driver for the active contraction of the heart. Due to different implementations of the calcium dynamics, simulating c...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
2021-10-01
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| Series: | Current Directions in Biomedical Engineering |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/cdbme-2021-2064 |
| _version_ | 1798030115682123776 |
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| author | Appel Stephanie Gerach Tobias Dössel Olaf Loewe Axel |
| author_facet | Appel Stephanie Gerach Tobias Dössel Olaf Loewe Axel |
| author_sort | Appel Stephanie |
| collection | DOAJ |
| description | Today a variety of models describe the physiological behavior of the heart on a cellular level. The intracellular calcium concentration plays an important role, since it is the main driver for the active contraction of the heart. Due to different implementations of the calcium dynamics, simulating cardiac electromechanics can lead to severely different behaviors of the active tension when coupling the same tension model with different electrophysiological models. To handle these variations, we present an optimization tool that adapts the parameters of the most recent, human based tension model. The goal is to generate a physiologically valid tension development when coupled to an electrophysiological cellular model independent of the specifics of that model's calcium transient. In this work, we focus on a ventricular cell model. In order to identify the calcium-sensitive parameters, a sensitivity analysis of the tension model was carried out. In a further step, the cell model was adapted to reproduce the sarcomere length-dependent behavior of troponin C. With a maximum relative deviation of 20.3% per defined characteristic of the tension development, satisfactory results could be obtained for isometric twitch tension. Considering the length-dependent troponin handling, physiological behavior could be reproduced. In conclusion, we propose an algorithm to adapt the tension development model to any calcium transient input to achieve a physiologically valid active contraction on a cellular level. As a proof of concept, the algorithm is successfully applied to one of the most recent human ventricular cell models. This is an important step towards fully coupled electromechanical heart models, which are a valuable tool in personalized health care. |
| first_indexed | 2024-04-11T19:36:09Z |
| format | Article |
| id | doaj.art-552e0419ecf143148884ed73d87ecffb |
| institution | Directory Open Access Journal |
| issn | 2364-5504 |
| language | English |
| last_indexed | 2024-04-11T19:36:09Z |
| publishDate | 2021-10-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Current Directions in Biomedical Engineering |
| spelling | doaj.art-552e0419ecf143148884ed73d87ecffb2022-12-22T04:06:51ZengDe GruyterCurrent Directions in Biomedical Engineering2364-55042021-10-017225125410.1515/cdbme-2021-2064Adaptation of the Calcium-dependent Tension Development in Ventricular CardiomyocytesAppel Stephanie0Gerach Tobias1Dössel Olaf2Loewe Axel3Institute of Biomedical Engineering, Fritz-Haber-Weg 1,Karlsruhe, GermanyInstitute of Biomedical Engineering, Fritz-Haber-Weg 1,Karlsruhe, GermanyInstitute of Biomedical Engineering, Fritz-Haber-Weg 1,Karlsruhe, GermanyInstitute of Biomedical Engineering, Fritz-Haber-Weg 1,Karlsruhe, GermanyToday a variety of models describe the physiological behavior of the heart on a cellular level. The intracellular calcium concentration plays an important role, since it is the main driver for the active contraction of the heart. Due to different implementations of the calcium dynamics, simulating cardiac electromechanics can lead to severely different behaviors of the active tension when coupling the same tension model with different electrophysiological models. To handle these variations, we present an optimization tool that adapts the parameters of the most recent, human based tension model. The goal is to generate a physiologically valid tension development when coupled to an electrophysiological cellular model independent of the specifics of that model's calcium transient. In this work, we focus on a ventricular cell model. In order to identify the calcium-sensitive parameters, a sensitivity analysis of the tension model was carried out. In a further step, the cell model was adapted to reproduce the sarcomere length-dependent behavior of troponin C. With a maximum relative deviation of 20.3% per defined characteristic of the tension development, satisfactory results could be obtained for isometric twitch tension. Considering the length-dependent troponin handling, physiological behavior could be reproduced. In conclusion, we propose an algorithm to adapt the tension development model to any calcium transient input to achieve a physiologically valid active contraction on a cellular level. As a proof of concept, the algorithm is successfully applied to one of the most recent human ventricular cell models. This is an important step towards fully coupled electromechanical heart models, which are a valuable tool in personalized health care.https://doi.org/10.1515/cdbme-2021-2064human cardiac contractionparameter optimizationsensitivity analysiscomputer simulation |
| spellingShingle | Appel Stephanie Gerach Tobias Dössel Olaf Loewe Axel Adaptation of the Calcium-dependent Tension Development in Ventricular Cardiomyocytes Current Directions in Biomedical Engineering human cardiac contraction parameter optimization sensitivity analysis computer simulation |
| title | Adaptation of the Calcium-dependent Tension Development in Ventricular Cardiomyocytes |
| title_full | Adaptation of the Calcium-dependent Tension Development in Ventricular Cardiomyocytes |
| title_fullStr | Adaptation of the Calcium-dependent Tension Development in Ventricular Cardiomyocytes |
| title_full_unstemmed | Adaptation of the Calcium-dependent Tension Development in Ventricular Cardiomyocytes |
| title_short | Adaptation of the Calcium-dependent Tension Development in Ventricular Cardiomyocytes |
| title_sort | adaptation of the calcium dependent tension development in ventricular cardiomyocytes |
| topic | human cardiac contraction parameter optimization sensitivity analysis computer simulation |
| url | https://doi.org/10.1515/cdbme-2021-2064 |
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