Contribution of the Purkinje System in Initiation and Maintenance of Arrhythmias

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atmire.migration.oldid4416
dc.contributor.advisorVigmond, Edward J.
dc.contributor.advisorNygren, Anders
dc.contributor.authorBehradfar, Elham
dc.contributor.committeememberFear, Elise C.
dc.contributor.committeememberBerenfeld, Omer
dc.contributor.committeememberDavidsen, Jörn
dc.date.accessioned2016-05-10T17:13:43Z
dc.date.available2016-05-10T17:13:43Z
dc.date.issued2016
dc.date.submitted2016en
dc.description.abstractThe Purkinje system is the conduction network of the heart that facilitates coordinated ventricular contraction and couples to the myocardium at discrete sites called Purkinje-Myocyte Junctions (PMJs). Fine and intricate geometry of the Purkinje system have confined experimental observations, therefore density and distribution of PMJs and Purkinje system contribution during cardiac arrhythmia are unclear. This thesis presents a detailed computer simulation study that highlights the role of the Purkinje system and its interaction with ventricles in arrhythmogenesis and maintenance. Firstly, simulations were performed on a model of rabbit ventricles to explore Purkinje system contributions during ventricular fibrillation. A fractal method for growing the Purkinje system was implemented to allow construction of anatomically realistic Purkinje network and investigation of PMJ density. The role of the Purkinje system in maintaining the arrhythmia was assessed by analyzing reentry dynamics. Results showed that the activation pattern at PMJs had little consistency over time during functional reentry, and a Purkinje system with a higher PMJ density contributed more to reentrant arrhythmia; however, the overall dynamics of sustained reentry did not appear to be significantly affected by Purkinje system complexity and coupling strengths at PMJs. Secondly, the realistic model of the Purkinje system was used to investigate mechanisms through which reduced myocardial coupling, induced by ischemia, modify the interaction between the Purkinje system and ventricular tissue, and affect ventricular excitation pattern. Experimental and modeling results suggest that ischemia-induced closing of gap junctions activates normally quiescent PMJs due to reduced source-sink mismatch and as a result, increased the complexity of activation. Modeling results indicated that a higher number of functional PMJs can speed activation of tissue and compensate for effects of uncoupling in slowing activation of the ventricles. Finally, effects of a potential antiarrhythmic drug, dantrolene, on suppressing delayed afterdepolarizations (DADs) due to Calcium overload were modeled. In ventricular model, rapid pacing promoted triggered activity but only those arising in the Purkinje fibers could generate action potential that propagated throughout the myocardium. According to modeling results, dantrolene could eliminate DAD at the Purkinje level by blocking channels that are only present in the Purkinje system.en_US
dc.identifier.citationBehradfar, E. (2016). Contribution of the Purkinje System in Initiation and Maintenance of Arrhythmias (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25446en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/25446
dc.identifier.urihttp://hdl.handle.net/11023/3001
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectEngineering
dc.subjectEngineering--Biomedical
dc.subjectEngineering--Electronics and Electrical
dc.subject.classificationComputer modelingen_US
dc.subject.classificationPurkinje systemen_US
dc.subject.classificationVentricular fibrillationen_US
dc.subject.classificationIschemiaen_US
dc.subject.classificationAfterdepolarizationen_US
dc.subject.classificationCardiac arrhythmiaen_US
dc.titleContribution of the Purkinje System in Initiation and Maintenance of Arrhythmias
dc.typedoctoral thesis
thesis.degree.disciplineElectrical and Computer Engineering
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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