Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/98709
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dc.contributor.advisorSanders, Prashanthan-
dc.contributor.advisorLau, Dennis Hui Sung-
dc.contributor.advisorBrooks, Anthony Graham-
dc.contributor.advisorKuklik, Pawel-
dc.contributor.authorThanigaimani, Shivshankar-
dc.date.issued2015-
dc.identifier.urihttp://hdl.handle.net/2440/98709-
dc.description.abstractHypertension is a major independent risk factor for atrial fibrillation (AF). Despite various clinical and experimental studies on atrial remodeling in hypertensive substrates, pre-clinical experimental studies involving the prevention and treatment of electrical and structural changes secondary to hypertension remain limited. Many antihypertensive drugs have been shown to reduce AF recurrence in patients with hypertension. Additionally, recent work suggests that anti-fibrotic drug, Tranilast, has beneficial effects in preventing AF. This thesis focuses on the electrophysiological and structural effects with anti-fibrotic and anti-hypertensive therapies in hypertensive large animal model. Chapter 1 details the theoretical mechanisms involved in the initiation and maintenance of AF and various conditions that contributes to abnormal atrial substrate formation. Importantly, studies involving reverse remodeling of various substrates and possible prevention of pathological atrial remodeling are also discussed. Chapter 2 details the histological, anatomical and molecular changes in the hypertensive atria. We demonstrated that hypertension resulted in structural remodeling through increased myocyte hypertrophy, endomysial and interstitial fibrosis and inflammation along with increased septal thickness, which was contributed by increased CTGF and TGF-ß₁ and reduced connexin43 expressions. Further, we showed that anti-hypertensive treatments could reverse all these pathological changes. This highlights the important role of aggressive blood pressure lowering therapy in patients with AF and hypertension. Chapter 3 illustrates the reverse electrical remodeling of hypertensive substrate using anti-hypertensive therapies. Significant improvement in conduction abnormalities and reduction in susceptibility to AF were seen with anti-hypertensive treatments. This further affirms the importance of blood pressure control in patients with hypertension and AF. Chapter 4 details the histological, anatomical and molecular changes leading to the prevention of remodeling process in hypertensive atria. Tranilast (anti-fibrotic) treatment resulted in prevention of atrial structural remodeling by preventing myocyte hypertrophy, endomysial and interstitial fibrosis, inflammation, septal thickness and altered CTGF, TGF-ß₁ and connexin43 expression levels. Chapter 5 illustrates the prevention of atrial electrical remodeling in hypertensive atria with tranilast treatment during the development of high blood pressure. The results showed a reduced susceptibility to AF by preventing conduction slowing and heterogeneity seen with hypertension. Importantly, the beneficial effects seen in chapter 4 & 5 with tranilast treatment were independent of blood pressure levels. Chapter 6 examines the fibrillatory electrograms in hypertensive atria. Complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) are thought to represent substrate sites in AF. A novel index of spatio-temporal stability (STS) was used in this study. We found that STS of CFAE was able to better predict AF termination than absolute mean fractionation values.en
dc.subjectatrial fibrillationen
dc.subjecthypertensionen
dc.subject1K1C ovine modelen
dc.subjectFibrosisen
dc.subjectinflammationen
dc.subjectConnexin43en
dc.subjectTGF-B1en
dc.subjectCTGFen
dc.subjectCFAEen
dc.subjectDFen
dc.subjectspatio-temporal complexityen
dc.titleAtrial reverse remodeling in hypertensive substrateen
dc.typeThesesen
dc.contributor.schoolSchool of Medicineen
dc.provenanceThis 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/legalsen
dc.description.dissertationThesis (Ph.D.) -- University of Adelaide, School of Medicine, 2015.en
Appears in Collections:Research Theses

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