In silico investigations into human ventricular pro-arrhythmic mechanisms combined with in vivo and in vitro experiments
<p>Sudden cardiac death (SCD) is one of the largest causes of natural mortality throughout the world. SCD can be triggered through ventricular arrhythmias due to many pathological conditions, including coronary artery diseases, arrhythmogenic cardiomyopathies and genetic mutations of ionic cha...
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| Format: | Thesis |
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2016
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| _version_ | 1797056507114684416 |
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| author | Zhou, X |
| author2 | Rodriguez, B |
| author_facet | Rodriguez, B Zhou, X |
| author_sort | Zhou, X |
| collection | OXFORD |
| description | <p>Sudden cardiac death (SCD) is one of the largest causes of natural mortality throughout the world. SCD can be triggered through ventricular arrhythmias due to many pathological conditions, including coronary artery diseases, arrhythmogenic cardiomyopathies and genetic mutations of ionic channel proteins. Although considerable research has been conducted to study proarrhythmic mechanisms, most studies were in animal models due to ethical limitations in human cardiac research. Therefore, more research is needed to investigate the proarrhythmic ionic mechanisms in human.</p> <p>In this thesis, we use biophysically-detailed models of human cardiac electrophysiology to explore the ionic mechanisms underlying several proarrhythmic conditions. A first study is to use traditional modeling approach to explore the effect of ionic remodelling in human epicardial border zone (EBZ) cells post myocardial infarction by introducing the analogous remodelling observed in canine. Sensitivity analysis of the human EBZ models leads to our interest in developing new techniques to include general variability into human cardiac electrophysiology research.</p> <p>Therefore, a novel methodology to include the effect of <em>in vivo</em> cardiac variability in human electrophysiology is developed in this study by constructing a population of models calibrated using <em>in vivo</em> human data. The experimentally-calibrated population of human ventricular cell models is then applied to investigate the proarrhythmic ionic mechanisms underlying cardiac alternans, and to test the effects of potential anti-arrhythmic drug therapies on alternans. We then explore the interaction between cardiac variability and a mutation of slow delayed rectifier potassium channel. Our simulation results reveal the complex interactions between different ionic components in the integrated electrophysiological system, highlighting the importance of cardiac variability in the development of proarrhythmic conditions.</p> |
| first_indexed | 2024-03-06T19:23:39Z |
| format | Thesis |
| id | oxford-uuid:1af82358-3552-4261-a105-4dd23da6c4df |
| institution | University of Oxford |
| last_indexed | 2024-03-06T19:23:39Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | oxford-uuid:1af82358-3552-4261-a105-4dd23da6c4df2022-03-26T10:57:43ZIn silico investigations into human ventricular pro-arrhythmic mechanisms combined with in vivo and in vitro experimentsThesishttp://purl.org/coar/resource_type/c_db06uuid:1af82358-3552-4261-a105-4dd23da6c4dfORA Deposit2016Zhou, XRodriguez, BOrovio, ABurrage, K<p>Sudden cardiac death (SCD) is one of the largest causes of natural mortality throughout the world. SCD can be triggered through ventricular arrhythmias due to many pathological conditions, including coronary artery diseases, arrhythmogenic cardiomyopathies and genetic mutations of ionic channel proteins. Although considerable research has been conducted to study proarrhythmic mechanisms, most studies were in animal models due to ethical limitations in human cardiac research. Therefore, more research is needed to investigate the proarrhythmic ionic mechanisms in human.</p> <p>In this thesis, we use biophysically-detailed models of human cardiac electrophysiology to explore the ionic mechanisms underlying several proarrhythmic conditions. A first study is to use traditional modeling approach to explore the effect of ionic remodelling in human epicardial border zone (EBZ) cells post myocardial infarction by introducing the analogous remodelling observed in canine. Sensitivity analysis of the human EBZ models leads to our interest in developing new techniques to include general variability into human cardiac electrophysiology research.</p> <p>Therefore, a novel methodology to include the effect of <em>in vivo</em> cardiac variability in human electrophysiology is developed in this study by constructing a population of models calibrated using <em>in vivo</em> human data. The experimentally-calibrated population of human ventricular cell models is then applied to investigate the proarrhythmic ionic mechanisms underlying cardiac alternans, and to test the effects of potential anti-arrhythmic drug therapies on alternans. We then explore the interaction between cardiac variability and a mutation of slow delayed rectifier potassium channel. Our simulation results reveal the complex interactions between different ionic components in the integrated electrophysiological system, highlighting the importance of cardiac variability in the development of proarrhythmic conditions.</p> |
| spellingShingle | Zhou, X In silico investigations into human ventricular pro-arrhythmic mechanisms combined with in vivo and in vitro experiments |
| title | In silico investigations into human ventricular pro-arrhythmic mechanisms combined with in vivo and in vitro experiments |
| title_full | In silico investigations into human ventricular pro-arrhythmic mechanisms combined with in vivo and in vitro experiments |
| title_fullStr | In silico investigations into human ventricular pro-arrhythmic mechanisms combined with in vivo and in vitro experiments |
| title_full_unstemmed | In silico investigations into human ventricular pro-arrhythmic mechanisms combined with in vivo and in vitro experiments |
| title_short | In silico investigations into human ventricular pro-arrhythmic mechanisms combined with in vivo and in vitro experiments |
| title_sort | in silico investigations into human ventricular pro arrhythmic mechanisms combined with in vivo and in vitro experiments |
| work_keys_str_mv | AT zhoux insilicoinvestigationsintohumanventricularproarrhythmicmechanismscombinedwithinvivoandinvitroexperiments |