Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686296
Title: Experimental and numerical investigation of arterial wall mass transport
Author: Chooi, Kok Yean
ISNI:       0000 0004 5918 4537
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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Abstract:
The accumulation of plasma macromolecules in the arterial intima is a critical step in atherogenesis. It depends on the balance between influx across the endothelium and efflux across the media. The work presented in this thesis investigated these phenomena. The distribution of 'hotspots' of high endothelial permeability around aortic branches was mapped in immature and mature rabbits; the pattern of disease at such sites changes with age. The pattern of hotspots of Evan's Blue dye-labelled albumin uptake was found to change with age. Using statistical techniques that account for spatial autocorrelation and non-linear relations between variables, a significant correlation with the pattern of cholesterol deposition was obtained at both ages. The hotspot patterns did not correlate with patterns of mitosis. The data also showed that the division of transendothelial transport pathways into 'small' and 'large' pores may represent an arbitrary division of a continuum of pore sizes. Albumin is smaller than the lipoproteins thought to trigger atherosclerosis. The study was therefore repeated using rhodamine-labelled 2 MDa dextran. In immature animals, the pattern of hotspots for this larger tracer was similar to the pattern for albumin. The mature pattern of dextran uptake differed from the immature one, but it was not the same as that observed for albumin. Further studies investigated transport through the media. As the transport of large molecules occurs predominantly by advection, characterising transmural water flux is important. Ex vivo experimental studies investigated effects of pressure and muscle contraction on hydraulic resistance. Numerical studies based on structural data from the ex vivo experiments were used to characterise the resistance of the media, and the intimal resistance was obtained by subtraction. Intimal and medial resistances in the order 1011 kg s⁻¹ m⁻² were found to change in opposite directions with increasing pressure or muscle contraction. The results may assist in understanding and preventing the development of atherosclerosis.
Supervisor: Weinberg, Peter ; Sherwin, Spencer Sponsor: British Heart Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.686296  DOI: Not available
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