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Computational modeling of nanodrug-induced effects on cardiac electromechanics
This work generally aims to promote the use of computational models for predicting side effects of nanodrugs under development, as a means to speed up the cycle of drug development, with potential savings on testing, and reduction in the need for animal or human testing. The specific objective o...
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2016
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| _version_ | 1867613409474772992 |
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| access_status_str | Open Access |
| author | Shalaby, Noha Mahmoud |
| author_browse | Shalaby, Noha Mahmoud |
| author_facet | Shalaby, Noha Mahmoud |
| author_sort | Shalaby, Noha Mahmoud |
| collection | Thesis |
| dc_rights_str_mv | The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. |
| description | This work generally aims to promote the use of computational models for predicting side effects of nanodrugs under development, as a means to speed up the cycle of drug development, with potential savings on testing, and reduction in the need for animal or human testing. The specific objective of this thesis has been to accurately model a single ventricular contraction-relaxation cycle, and monitor the effects induced by nanodrugs on the electro-mechano-physiology of the left and right ventricles. Nanodrug interaction with ion channels located on cardiac cell membranes, such as those for sodium, potassium and calcium, can distort an electrical wave propagating through the tissue and can affect cardiac macroscale functions. In this study, a material model after Holzapfel and Ogden was developed to account for the anisotropic hyperelastic behavior of cardiac tissue, which was implemented on the open source software library Chaste. A coupled drug-electro-mechano-physiological system was then set up, also on Chaste, where a nanodrug effect was introduced into the cellular structure (nanoscale) as an ion channel inhibitor, and its influence then solved for, with respect to resulting electro-mechanical ventricular behaviors. Using quantifiable biomarkers, these effects were compared to the literature and clinical data. In this work we identified the following main results. Nanodrugs causing sodium channel blockage were found to produce the anticipated delays in electro-mechanics. Our study further predicted additional effects on LV twisting and LV & RV strain. On the other hand, nanodrugs causing potassium and calcium channel blockage revealed that cardiac mechanics is less responsive to mild alterations in electrophysiology, than electrophysiology is to ionic changes. Nonetheless, it is important to quantify these changes, as even a very small deviation from normal could accumulate over multiple cardiac cycles, and lead to adverse consequences on cardiac health in the long term. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-1342 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:35:41.195Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2016 |
| publishDateRange | 2016 |
| publishDateSort | 2016 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-1342 Computational modeling of nanodrug-induced effects on cardiac electromechanics Shalaby, Noha Mahmoud This work generally aims to promote the use of computational models for predicting side effects of nanodrugs under development, as a means to speed up the cycle of drug development, with potential savings on testing, and reduction in the need for animal or human testing. The specific objective of this thesis has been to accurately model a single ventricular contraction-relaxation cycle, and monitor the effects induced by nanodrugs on the electro-mechano-physiology of the left and right ventricles. Nanodrug interaction with ion channels located on cardiac cell membranes, such as those for sodium, potassium and calcium, can distort an electrical wave propagating through the tissue and can affect cardiac macroscale functions. In this study, a material model after Holzapfel and Ogden was developed to account for the anisotropic hyperelastic behavior of cardiac tissue, which was implemented on the open source software library Chaste. A coupled drug-electro-mechano-physiological system was then set up, also on Chaste, where a nanodrug effect was introduced into the cellular structure (nanoscale) as an ion channel inhibitor, and its influence then solved for, with respect to resulting electro-mechanical ventricular behaviors. Using quantifiable biomarkers, these effects were compared to the literature and clinical data. In this work we identified the following main results. Nanodrugs causing sodium channel blockage were found to produce the anticipated delays in electro-mechanics. Our study further predicted additional effects on LV twisting and LV & RV strain. On the other hand, nanodrugs causing potassium and calcium channel blockage revealed that cardiac mechanics is less responsive to mild alterations in electrophysiology, than electrophysiology is to ionic changes. Nonetheless, it is important to quantify these changes, as even a very small deviation from normal could accumulate over multiple cardiac cycles, and lead to adverse consequences on cardiac health in the long term. 2016-06-01T07:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/343 https://fount.aucegypt.edu/context/etds/article/1342/viewcontent/NohaShalabyThesis.pdf The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. Theses and Dissertations AUC Knowledge Fountain Nanodrugs Cardiac mechanics |
| spellingShingle | Nanodrugs Cardiac mechanics Shalaby, Noha Mahmoud Computational modeling of nanodrug-induced effects on cardiac electromechanics |
| title | Computational modeling of nanodrug-induced effects on cardiac electromechanics |
| title_full | Computational modeling of nanodrug-induced effects on cardiac electromechanics |
| title_fullStr | Computational modeling of nanodrug-induced effects on cardiac electromechanics |
| title_full_unstemmed | Computational modeling of nanodrug-induced effects on cardiac electromechanics |
| title_short | Computational modeling of nanodrug-induced effects on cardiac electromechanics |
| title_sort | computational modeling of nanodrug induced effects on cardiac electromechanics |
| topic | Nanodrugs Cardiac mechanics |
| url | https://fount.aucegypt.edu/etds/343 https://fount.aucegypt.edu/context/etds/article/1342/viewcontent/NohaShalabyThesis.pdf |
| work_keys_str_mv | AT shalabynohamahmoud computationalmodelingofnanodruginducedeffectsoncardiacelectromechanics |