A Computational Study of Blood Flow and Vascular Nitric Oxide Transport

Abstract

Atherosclerosis occurs in a spatially heterogeneous fashion within the arterial system. The patchy nature of the disease is thought to reflect spatial variation in haemodynamic factors such as wall shear stress (WSS) and in the concentration of vascular species. This thesis numerically investigates blood flow and vascular transport of the atheroprotective agent nitric oxide (NO) using a spectral/hp element method. Firstly, NO distribution is analysed within a parallel-plate flow chamber coated with endothelial cells. Contrary to the accepted hypothesis that NO concentration increases with WSS (as does NO production), it is observed that NO concentration depends on WSS in a non-monotonic fashion. Furthermore, these results emphasise the effect of convection on in vitro NO transport, which has been overlooked or misinterpreted in most previous computational studies. Secondly, blood flow and NO transport are investigated within a detailed representation of the rabbit thoracic aorta and its branches, which was reconstructed using high resolution computed tomography (CT) scan data of a vascular corrosion cast. The computed WSS distribution exhibits significant spatial heterogeneity, reflecting the complexity of the blood flow. In particular it is observed that two Dean-type vortices (associated with a skewed velocity profile) form in the aortic arch and propagate along the descending aorta. This results in streaks of WSS similar in nature to the fatty streaks of early stage atherosclerosis observed in mature rabbits. This finding provides further support for the hypothesis that blood flow mediates atherogenesis. The vascular distribution of NO is found to depend significantly on the relationship between NO production and WSS. Furthermore, it is concluded that mechanisms preventing NO consumption by haemoglobin (such as diffusional barriers) must exist in order for NO to exert its atheroprotective action. This study represents the first effort to model NO transport in a realistic representation of the major arteries.