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Title: Microcirculatory and myocardial physiology in ischaemic left ventricualr dysfunction
Author: De Silva, Kalpa
ISNI:       0000 0004 5366 5989
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2014
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Introduction: Left ventricular (LV) dysfunction influences, and is affected by, changes in coronary flow. The integrity of the microvasculature is integral in myocardial perfusion and myocyte function, and remains incompletely understood in the context of impaired LV function. The main aim of this thesis was to examine the physiological alterations that occur to the microcirculation and myocardial function following myocardial infarction. Methods: Simultaneous intra-coronary pressure and Doppler flow assessment with wave intensity analysis performed to determine the energy flux in the coronary circulation was undertaken following percutaneous revascularization, in two distinct cohorts. Firstly, in a group with recent myocardial infarction and secondly in a group undergoing revascularization supported by intra-aortic balloon counterpulsation {IABP) therapy. In a separate group, the electrophysiological alterations occurring following acute myocardial infarction were assessed using a novel trans-coronary epicardial voltage mapping technique. Results: We demonstrated that the microcirculatory expansion wave in the infarct-related artery is predictive of both infarct size and regional ventricular recovery following revascularization, assessed by cardiac MRI. Intra-aortic balloon inflation was temporally associated with a unique acceleratory aortic-originating compression wave energy. The magnitude of this wave relates linearly to augmentation of coron y flow velocity during hyperaemic conditions, where autoregulation is 'switched-off'. During basal, 'switched-on' autoregulatory conditions, IABP therapy does not significantly augment flow, due to an increase in microvascular resistance and reduction in microcirculatory expansion wave energy. Trans-coronary electrogram mapping is technically feasible during percutaneous revascularization procedures, with encouraging results in regard to voltage-mapped parameters that may allow prediction of infarcted versus viable tissue. Conclusion: The microcirculation is integral in the functioning of the myocardium. Wave energy derivatives provide an integrated assessment of microvascular haemodynamics and regional myocardial function. Furthermore, the efficacy of intra-aortic balloon counterpulsation is likely to be dependent on the degree of microvascular dysfunction present, with those whose salient haemodynamics are beyond the autoregulatory range most likely to benefit from mechanical assist support devices. Trans-coronary epicardial voltage mapping may provide a technique for the assessment of myocardial viability following infarction, though further development is required to determine its utility and accuracy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available