The objective of this thesis is to investigate the pathophysiology of the coronary slow phenomenon (CSFP). The experimental work of this thesis has taken a 'bedside to benchtop' approach with clinical observations made in the second chapter guiding the application of basic research techniques in subsequent chapters. Chapter 1 ; The CSFP is a disorder of the coronary microcirculation ; hence chapter 1 specifically reviews the current understanding of this vascular territory and concludes with a summary of the clinical disorders affecting it, concentrating on the CSFP. Chapter 2 ; investigated the angiographic response of the CSFP to a calcium channel blocking agent with antianginal efficacy in this disorder ( mibefradil ). Mibefradil administration was associated with an acute improvement of coronary flow indices which occurred despite background vasodilator therapy with conventional calcium channel antagonists. Chapter 3 ; investigated the in vitro response of human microvessels to mibefradil in comparison to conventional calcium channel blockers. Mibefradil was found to be a more potent agent both in terms of vasodilatation and the prevention of vasoconstriction. Both findings support the clinical observations and point to its selective action on the calcium T channel subtype as a potential mechanism. Chapter 4 ; examined the expression of T type calcium channels at the level of the microvasculature and compared T channel expression in CSFP patients and controls. T channels were found to be expressed at two or more orders of magnitude greater than the L channels. No difference in T channel expression between patients and controls was found. Chapter 5 ; examined the vasomotor reactivity of isolated subcutaneous arterial microvessels to various vasoactive substances between controls and CSFP patients. CSFP patients were found to have a selective hyper reactivity to endothelin. Chapter 6 ; examined plasma endothelin levels in CSFP patients and controls and the relationship between endothelin levels and angina frequency in the CSFP cohort. A small but statistically significant elevation of endothelin-1 was present in patients with the CSFP. A positive association between plasma endothelin fluctuation and angina frequency was also found in the CSFP cohort but not between absolute endothelin levels and angina symptoms. / Thesis (Ph.D.)-- The University of Adelaide, School of Medical Sciences, 2006.
| Identifer | oai:union.ndltd.org:ADTP/274270 |
| Date | January 2006 |
| Creators | Turner, Stuart Peter |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
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