Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (M.A.)--York University, 2004. Graduate Programme in Psychology. / Typescript. Includes bibliographical references (leaves 75-85). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url%5Fver=Z39.88-2004&res%5Fdat=xri:pqdiss&rft%5Fval%5Ffmt=info:ofi/fmt:kev:mtx:dissertation&rft%5Fdat=xri:pqdiss:MQ99367

Atrial fibrillation and atrial flutter are the most common sustained arrhythmias, however their underlying mechanisms are yet to be fully characterised. This thesis evaluates the electrophysiological and electroanatomical substrate of the atria in patients with these arrhythmias. Experimental studies of atrial fibrillation have demonstrated effective refractory period shortening and conduction slowing as a result of atrial fibrillation giving rise to the concept that "atrial fibrillation begets atrial fibrillation". However, cardioversion to prevent electrical remodelling does not prevent progression of disease, suggesting a "second factor" drives this process. Chapters 2 and 3 evaluate the atrial substrate in patients with "lone" atrial fibrillation. These studies demonstrate such patients, remote from an arrhythmic event, have prolongation of atrial refractoriness, conduction slowing, impairment of sinus node function, site-specific conduction delay, lower voltage and a greater proportion of complex electrograms compared to reference patients. These abnormalities constitute the "second factor" critical to the development and progression of atrial fibrillation. Atrial flutter has a close inter-relationship with atrial fibrillation and these rhythms frequently co-exist. Atrial fibrillation often occurs in patients with heart disease known to demonstrate abnormal atrial substrate; whether similar substrate exists in patients with atrial flutter to account for the co-existence of both arrhythmias is unknown. Chapters 4 and 5 evaluate the atrial substrate in patients with atrial flutter, remote from arrhythmia, demonstrating structural abnormalities characterised by loss of myocardial voltage, conduction slowing and impaired sinus node function, without reduction in atrial refractoriness. These findings implicate a common substrate as the cause of the close inter-relationship between these arrhythmias. There is a frequent association between atrial arrhythmia and sinus node disease for which several mechanisms have been postulated. In addition, there is a size discrepancy between the anatomical sinus node and the much larger functional sinus node complex. little is known about normal sinus node function or the effects of remodelling due to arrhythmia. Chapter 6 characterises sinus node activation to determine the nature and extent of the functional sinus node complex in patients with and without chronic atrial flutter. The functional sinus node complex demonstrates dynamic shifts in activation with preferential pathways of conduction to atrial myocardium. Patients with atrial flutter demonstrate lesser voltage, longer conduction times along preferential pathways and a smaller functional sinus node complex. These findings provide insights into the function of the human sinus node in health and disease. Sites of complex fractionated atrial electrograms and highest dominant frequency are implicated in maintaining atrial fibrillation. Chapter 7 determines the minimum recording duration that accurately characterises electrogram complexity and activation frequency. An electrogram duration of 5 seconds is required to accurately identify these sites. Chapter 8 evaluates the relationship between sites of fractionation and high frequency activation during atrial fibrillation. Greater fractionation and higher dominant frequency are seen in persistent atrial fibrillation and left atria. Preferential areas of high dominant frequency are observed in paroxysmal but not persistent atrial fibrillation. Areas of complex fractionated atrial electrograms are found adjacent to sites of high dominant frequency. / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2009

Atrial arrhythmias are the most prevalent sustained cardiac arrhythmias. Rates of hospitalisation and costs incurred to healthcare organisations are increasing in epidemic proportions. Despite this, the mechanisms of the transition from sinus rhythm to arrhythmic states are not well understood. The high level of regional electrical heterogeneity observed in the atria is thought to contribute towards the high prevalence of atrial arrhythmias. However, current computer models of the intact human atria only account for a small degree of this regional electrical heterogeneity, and do not include descriptions of the pacemaker regions of the sinoatrial node and the atrioventricular node. In this project, a new computational model of the intact 3D human atria is developed. First, a new single cell model to simulate the electrical action potential of the human atrial myocyte is developed. This model more accurately simulated the experimentally observed properties of human atrial action potentials than previous models. A family of electrically heterogeneous models describing the major regions within the atria is then developed, including those of the sinoatrial- and atrioventricular- nodes. This set of regional cell models represents the most expansive and complete set currently available. It is demonstrated that the large range of different electrical properties results in a large range of action potential morphology and duration within the atria. Models of the effect of sympathetic and parasympathetic regulation on the electrical AP of the models of the atrial working myocardium and the pacemaker regions were also incorporated. This demonstrated that sympathetic regulation can increase the pacing rate of the sinoatrial node and the atrio-ventricular node, and has a complex dose dependent effect on the atrial working myocardium. Four distinct models of the effects of atrial fibrillation induced remodelling on the atrial working myocardium are developed. These characterised the effect of remodelling of IKur on the overall changes in action potential morphology and duration observed. It is shown that the presence or absence of remodelling of this channel accounts for two distinct observed morphologies. A previous 3D anatomical model of the human atria is improved. First, detailed anatomical models for the sinoatrial node and the atrioventricular node are incorporated into the model. Second, it is further segmented to include regions for the pulmonary veins, atrio-ventricular ring, atrial septum and sinoatrial node block zone. This model is used to investigate the effects of sympathetic and parasympathetic regulation in the 3D atria. Finally, a detailed investigation of the underlying mechanisms of atrial fibrillation in the 3D atria, and the effect of electrical remodelling on the behaviour of atrial fibrillation, is performed using the detailed 3D model. This work represents a significant advance in 3D human atrial modelling. The anatomical model incorporates a greater level of complexity than previous models, and for the first time allowed investigation of the pacemaking mechanisms in the 3D intact human atria. The atrial fibrillation protocols are more physiologically relevant than previous models and have elucidated the roles that electrophysiological remodelling, electrical heterogeneity and structural anisotropy play in the development and maintenance of atrial fibrillation.