{"id":{"repo_id":"washington","oai_identifier":"oai:digital.lib.washington.edu:1773/50232"},"canonical_url":"https://search.dev.ndltd.org/etd/washington/oai:digital.lib.washington.edu:1773/50232","repository":{"repo_id":"washington","name":"University of Washington","base_url":"https://digital.lib.washington.edu/server/oai/request"},"display":{"title":"Controlling Arrhythmias Using Optogenetic Actuators in Computational Simulations","abstract":"This dissertation discusses the application of light-induced stimulation (optogenetics) in computational models of heart cells (cardiomyocytes), cardiac tissues, and heart chambers to control arrhythmia development. Chapter 1 presents an overview of cardiac anatomy, relevant physiology, and cardiac electrophysiology computational models. Chapter 2 provides a basic explanation of optogenetic actuators (opsins), covering past applications (both experimental and computational) in cardiac tissue at various scales. Chapter 3 examines the efficacy of expressing an anion-conducting opsin (GtACR1) to terminate atrial and ventricular arrhythmias in 3D patient-derived models. Additionally, a 2-state photocurrent model for GtACR1 is introduced. Chapter 4 studies the use of subthreshold optogenetic stimulation to up- and down-regulate early afterdepolarization propensity (cell-scale) and related premature ventricular complexes (organ-scale) in patient models. Chapter 5 evaluates the use of optogenetic stimulation to modulate spontaneous beating in pluripotent stem cell-derived cardiomyocytes (cell-scale) and graft-to-host excitation in 2D, histology-derived tissue models (tissue-scale). The work presented here demonstrates how optogenetic stimulation can be used to control the initiation and suppression of arrhythmias in computational models across a variety of arrhythmia-prone conditions.","abstract_html":"This dissertation discusses the application of light-induced stimulation (optogenetics) in computational models of heart cells (cardiomyocytes), cardiac tissues, and heart chambers to control arrhythmia development. Chapter 1 presents an overview of cardiac anatomy, relevant physiology, and cardiac electrophysiology computational models. Chapter 2 provides a basic explanation of optogenetic actuators (opsins), covering past applications (both experimental and computational) in cardiac tissue at various scales. Chapter 3 examines the efficacy of expressing an anion-conducting opsin (GtACR1) to terminate atrial and ventricular arrhythmias in 3D patient-derived models. Additionally, a 2-state photocurrent model for GtACR1 is introduced. Chapter 4 studies the use of subthreshold optogenetic stimulation to up- and down-regulate early afterdepolarization propensity (cell-scale) and related premature ventricular complexes (organ-scale) in patient models. Chapter 5 evaluates the use of optogenetic stimulation to modulate spontaneous beating in pluripotent stem cell-derived cardiomyocytes (cell-scale) and graft-to-host excitation in 2D, histology-derived tissue models (tissue-scale). 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Chapter 1 presents an overview of cardiac anatomy, relevant physiology, and cardiac electrophysiology computational models. Chapter 2 provides a basic explanation of optogenetic actuators (opsins), covering past applications (both experimental and computational) in cardiac tissue at various scales. Chapter 3 examines the efficacy of expressing an anion-conducting opsin (GtACR1) to terminate atrial and ventricular arrhythmias in 3D patient-derived models. Additionally, a 2-state photocurrent model for GtACR1 is introduced. Chapter 4 studies the use of subthreshold optogenetic stimulation to up- and down-regulate early afterdepolarization propensity (cell-scale) and related premature ventricular complexes (organ-scale) in patient models. Chapter 5 evaluates the use of optogenetic stimulation to modulate spontaneous beating in pluripotent stem cell-derived cardiomyocytes (cell-scale) and graft-to-host excitation in 2D, histology-derived tissue models (tissue-scale). The work presented here demonstrates how optogenetic stimulation can be used to control the initiation and suppression of arrhythmias in computational models across a variety of arrhythmia-prone conditions."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Controlling Arrhythmias Using Optogenetic Actuators in Computational Simulations"]}]}],"canonical_facts":{"dc:contributor.advisor":["Boyle, Patrick M"],"dc:creator":["Ochs, Alexander Richard"],"dc:date.accessioned":["2023-08-14T17:02:19Z"],"dc:date.available":["2023-08-14T17:02:19Z"],"dc:date.issued":["2023-08-14"],"dc:description":["Thesis (Ph.D.)--University of Washington, 2023"],"dc:description.abstract":["This dissertation discusses the application of light-induced stimulation (optogenetics) in computational models of heart cells (cardiomyocytes), cardiac tissues, and heart chambers to control arrhythmia development. 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