The pathophysiology of the coronary slow flow phenomenon
Date
2006
Authors
Turner, Stuart Peter
Editors
Advisors
Beltrame, John Francis
Koblar, Simon Andrea
Koblar, Simon Andrea
Journal Title
Journal ISSN
Volume Title
Type:
Thesis
Citation
Statement of Responsibility
Conference Name
Abstract
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.
School/Discipline
School of Medical Sciences
Dissertation Note
Thesis (Ph.D.)-- The University of Adelaide, School of Medical Sciences, 2006.