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dc.contributor.advisorBeltrame, John Francisen
dc.contributor.advisorKennedy, Jennifer Annen
dc.contributor.authorKopetz. Victoriaen
dc.description.abstractBackground: This thesis investigates the clinical and biological factors that contribute to the cardiovascular condition known as the Coronary Slow Flow Phenomenon (CSFP). From its initial description, little remains understood regarding the mechanisms contributing to this curious condition. The research efforts in this thesis have focused upon further characterising the CSFP and identifying an effective therapy, by investigating the mechanisms involved during different periods of presentation. The specific objectives include: 1) Identifying the possible mechanisms of the acute coronary syndrome (ACS) presentation in CSFP patients by comparing plasma protein profiles from samples obtained from initial presentation and during a quiescent phase of the disorder; 2) Investigating the role of the endothelium during the chronic phase of the disorder. Specifically, this includes looking at mechanisms of endothelial dysfunction, inflammation and oxidative stress and comparisons with a healthy control group; 3) Evaluating the efficacy of a dual endothelin-1 (ET-1) receptor blocker (Bosentan) in ameliorating angina symptoms in CSFP patients. This project also involves monitoring improvements in health-related quality of life, clinical profiles, endothelial function, inflammation and oxidative stress following Bosentan treatment. Methods This thesis employed a number of methods to comprehensively assess the pathophysiological mechanisms contributing to CSFP aetiology. In order to identify possible protein biomarker candidates, a state-of-the-art proteomic approach was used to obtain plasma protein profiles. A paired-longitudinal study design was employed by which blood samples were obtained from CSFP patients during the ACS and compared to a quiescent phase. During the chronic phase of the condition, a cross-sectional study was conducted to assess endothelial function, inflammation and oxidative stress parameters compared with a healthy control group that had no history of chest pain or coronary disease. The clinical trial employed a randomised, double-blind, placebo-controlled, cross-over design that involved evaluating changes in chest pain, clinical characteristics, endothelial function, inflammation and oxidative stress parameters following treatment with bosentan therapy Summary of major findings: The above studies yielded the following findings: 1) Proteomic investigations identified specific inflammatory and oxidative stress protein markers that were elevated during the ACS presentation compared to the chronic phase (Chapter 2). 2) There was no evidence of impairments in endothelial vasomotor function or increases in inflammatory and oxidative stress parameters during the chronic phase of the condition compared to control subjects (Chapter 3). 3) Bosentan therapy did not significantly improve angina symptoms, clinical profiles, endothelial function, inflammation and oxidative stress parameters compared to placebo. Despite not reaching statistical significance, reductions in angina frequency and severity in addition to improvements in quality of life parameters were identified (Chapter 4). Conclusion: This thesis provides a new platform for future investigations into the CSFP. Pathophysiological differences identified between the acute and chronic presentations have initiated the need to further conduct research on the specific mechanisms that contribute to both the ACS presentation and persistent symptoms. Additionally, investigating the role of ET-1 receptor blockade in CSFP patients has identified a number of inherent problems associated with clinical trial design in CSFP patients.en
dc.subjectcoronary microvascular disease; proteomics; endothelial functionen
dc.titleClinical and biological determinants of the coronary slow flow phenomenon.en
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:
dc.description.dissertationThesis (Ph.D.) -- University of Adelaide, School of Medicine, 2012en
Appears in Collections:Research Theses

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