Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/111992
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Type: Theses
Title: Atrial electrophysiological and structural changes in obesity and diabetes mellitus
Author: Neo, Melissa
Issue Date: 2017
School/Discipline: Adelaide Medical School
Abstract: Atrial fibrillation (AF) is the most commonly presented arrhythmia in the clinical setting, and its prevalence contributes significantly towards morbidity and mortality rates in the general population. Obesity and diabetes mellitus (DM, type I and type II DM) are recognised, well established independent risk factors of AF which can occur and contribute towards the development of AF both individually and in a concomitant fashion. The pathophysiological processes by which a proarrhythmic atrial substrate is produced in obesity and DM have not been fully elucidated. Further characterisation of the atrial substrate in obesity and DM induced AF is required. Chapter one addresses the mechanistic components which may contribute towards establishing AF, and discusses the early and current insights underlying the pathogenesis of AF; This chapter describes the current literature available on the electrophysiological and structural components which may lead to the development of a vulnerable atrial substrate; these include the role of the action potential (AP), the relationship between the AP and the effective refractory period (ERP), and the contribution of inflammation and fibrosis towards AF development. Chapter two investigates the feasibility and result of combined application of simultaneous high density conduction mapping with intracellular membrane potential recording to better understand the genesis and maintenance of arrhythmias in the isolated atria. Described are the ability to observe changes in action potential (AP) morphology at a given recording region, regional differences in AP restitution, lack of correlation between AP duration (APD) and the atrial effective refractory period (ERP), and AP alternans in amplitude, and, duration. Chapter three assesses electrophysiological and structural changes in a rat model of type I DM (T1DM) using streptozotocin (STZ), which preferentially exerts toxicity to the insulin-producing beta cells of the pancreas to elicit the T1DM phenotype. This chapter demonstrates the impact of untreated T1DM on the atrial myocardium. At the structural level, T1DM animals demonstrated atrial cardiomyocyte hypertrophy with increased fibrosis. At the electrophysiological level, there was an abbreviation of the ERP with increased heterogeneity in conduction, as well as prolongation of the AP. Chapter four describes the impact of obesity, type II DM (T2DM) and age on the electrical and structural properties of the atria using the Zucker (fa/fa) rat model. This chapter reports cardiomyocyte hypertrophy, increased fibrosis, prolongation of the APD, increased heterogeneity and slowed conduction, with differences in ERP between the left and right atrium of the DM animals. These results highlight the potential difference between the pathogenesis of T2DM from T1DM on the atrial myocardium in the predisposition towards development of AF. Chapter five summarises the observations made in the T1DM and T2DM studies of chapters three and four respectively; this chapter discusses the similarities and differences shared in the data obtained from the studies, with a brief description of the potential mechanisms involved in DM-induced pathogenesis of AF, Additionally, the potential importance of segregating the diabetic states as having individual and differential influences on the atrial myocardium is highlighted. Future directions and areas of further research conclude this chapter.
Advisor: Saint, David Albert
Sanders, Prashanthan
Dissertation Note: Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, Adelaide Medical School, 2017.
Keywords: atrial fibrillation
diabetes mellitus
obesity
structural remodeling
electrophysiological remodeling
Research by Publication
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals
DOI: 10.4225/55/5af3a17f69af9
Appears in Collections:Research Theses

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