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https://hdl.handle.net/2440/87364
Type: | Thesis |
Title: | Implications of catecholamine-related pathophysiology in cardiomyopathy. |
Author: | Nguyen, Thanh Ha |
Issue Date: | 2012 |
School/Discipline: | School of Medicine |
Abstract: | Although secretion of catecholamines is critical to cardiovascular homeostasis, there is ample evidence that prolonged or marked catecholamine release may engender cardiovascular dysfunction, both in the short and long term. The processes involved include induction of oxidative stress and of inflammation, and the consequences include cell death (apoptosis), resultant fibrosis and both temporary and permanent contractile dysfunction of the heart. Congestive heart failure, both acute and chronic, represents a condition in which catecholamine effects are ultimately deleterious, and indeed many treatments of heart failure target this anomaly. The subject of this thesis is an examination of two particular aspects of catecholamine-related cardiovascular pathophysiology. The first issue examined is the phenomenon of (autonomic) cardiac denervation, a process which occurs extensively in CHF and leads, via impaired catecholamine re-uptake, to increased tissue exposure to catecholamines. The second is Tako-tsubo cardiomyopathy (TTC), a form of “stress-induced” cardiomy-opathy occurring predominantly in post-menopausal women, and apparently precipitated at least in part by bursts of catecholamine hypersecretion. The study of CHF utilised the technique of ¹²³I-MIBG imaging to quantitate cardiac denervation. The implications of the extent of denervation on (a) evolution of LV dysfunction and (b) late arrhythmogenesis were examined in a cohort of 45 patients. The data showed no significant association between extent of denervation and either of these endpoints. The results therefore cast into question the potential utility of such technique as a means of prognostication and therapeutic decision-making in patients with CHF. The studies concerning TTC have two major components: (a) an examination of the release of natriuretic peptides in association with TTC, and the potential for this release to be of diagnostic utility in the disease. and (b) an evaluation of nitric oxide (NO) signalling in the acute and recovery phase of TTC. Studies with brain natriuretic peptide (BNP) and its inactive co-product, N-terminal proBNP (NT-proBNP), revealed that plasma levels were markedly elevated in TTC, that extent of elevation correlated both with catecholamine markers and with severity of the individual attack, and the levels remained elevated for at least 3 months. Furthermore, comparison with a cohort of age-matched females who presented with acute myocardial infarction (AMI) suggested that NT-proBNP levels might form part of a diagnostic algorithm to separate TTC from AMI. Studies with NO signalling were initiated in the expectancy that this would be impaired in TTC. However, it was found that there was “paradoxical” accentuation of NO effects and of biochemical determinants of NO formation in TTC. Despite the apparently paradoxical nature of these findings, it is proposed that the adverse impact of catecholamines on the heart in TTC might be potentiated by products of the NO signalling cascade. In summary, these studies provide new insights into mechanisms of catecholamine toxicity on the heart, and hint at relationships between catecholamines, natriuretic peptides, and NO as complex modulation of both injury and recovery. On the other hand, the CHF studies suggest that extensive treatment with agents such as angiotensin converting enzyme inhibitors (ACEI) and β-adrenoceptor antagonists may blunt cardiac toxicity of catecholamines. |
Advisor: | Unger, Steven Anthony Horowitz, John David |
Dissertation Note: | Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2012 |
Keywords: | catecholamines; cardiomyopathy; chronic heart failure; Takotsubo cardiomyopathy |
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 |
Appears in Collections: | Research Theses |
Files in This Item:
File | Description | Size | Format | |
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01front.pdf | 127.47 kB | Adobe PDF | View/Open | |
02whole.pdf | 5.73 MB | Adobe PDF | View/Open | |
Permissions Restricted Access | Library staff access only | 222.85 kB | Adobe PDF | View/Open |
Restricted Restricted Access | Library staff access only | 5.73 MB | Adobe PDF | View/Open |
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