Haemodynamics in the mouse aortic arch computed from MRI-derived velocities at the aortic root.

Mice are widely used to investigate atherogenesis, which is known to be influenced by stresses related to blood flow. However, numerical characterization of the haemodynamic environment in the commonly studied aortic arch has hitherto been based on idealizations of inflow into the aorta. Our purpose in this work was to numerically characterize the haemodynamic environment in the mouse aortic arch using measured inflow velocities, and to relate the resulting shear stress patterns to known locations of high- and low-lesion prevalence. Blood flow velocities were measured in the aortic root of C57/BL6 mice using phase-contrast MRI. Arterial geometries were obtained by micro-CT of corrosion casts. These data were used to compute blood flow and wall shear stress (WSS) patterns in the arch. WSS profiles computed using realistic and idealized aortic root velocities differed significantly. An unexpected finding was that average WSS in the high-lesion-probability region on the inner wall was actually higher than the WSS in the low-probability region on the outer wall. Future studies of mouse aortic arch haemodynamics should avoid the use of idealized inflow velocity profiles. Lesion formation does not seem to uniquely associate with low or oscillating WSS in this segment, suggesting that other factors may also play a role in lesion localization.

Design optimization of a helical endothelial cell culture device.

The specific roles of mass transfer and fluid dynamic stresses on endothelial function, important in atherogenesis, are not known. Further, the effects of mass transfer and fluid dynamic stresses are difficult to separate because areas of "abnormal" mass transfer and "abnormal" wall shear stress tend to co-localize (where abnormal is defined as any deviation from the mass transfer rate or wall shear stress present in a long straight artery with the same flow rate and diameter). Our goal was to design a cell culture device which gives maximum separation between areas of abnormal shear stress and areas of abnormal mass transfer. We used design optimization principles to design a helical cell culture device. Using shear stress and mass transfer fields predicted by solving the governing equations, the area of the device which was exposed to low rates of mass transfer and normal levels of wall shear stress was determined. The design optimization method then maximized this area by varying the design variables, resulting in the optimum design. The optimum design had Reynolds number = 50, helical radius = 3.23 and helical pitch = 3.82. The area of the device which was exposed to low rates of mass transfer and regular levels of wall shear stress was about 4.5 times the inlet cross-sectional area of the device or about 5% of the device total internal surface area. An optimum design was successfully determined and the methodology used was shown to be robust. The area of the device which was exposed to low rates of mass transfer and regular levels of wall shear stress occurred in a defined region which should aid further experimental work.

Variations in mass transfer to single endothelial cells.

Mass transfer between flowing blood and arterial mural cells (including vascular endothelial cells) may play an important role in atherogenesis. Endothelial cells are known to have an apical surface topography that is not flat, and hence mass transfer patterns to individual endothelial cells are likely affected by the local cellular topography. The purpose of this paper is to investigate the relationship between vascular endothelial cell surface topography and cellular level mass transfer. Confluent porcine endothelial monolayers were cultured under both shear and static conditions and atomic force microscopy was used to measure endothelial cell topography. Using finite element methods and the measured cell topography, flow and concentration fields were calculated for a typical, small, blood-borne solute. A relative Sherwood number was defined as the difference between the computed Sherwood number and that predicted by the Leveque solution for mass transfer over a flat surface: this eliminates the effects of axial location on mass transfer efficiency. The average intracellular relative Sherwood number range was found to be dependent on cell height and not dependent on cell elongation due to shear stress in culture. The mass flux to individual cells reached a maximum at the highest point on the endothelial cell surface, typically corresponding to the nucleus of the cell. Therefore, for small receptor-mediated solutes, increased solute uptake efficiency can be achieved by concentrating receptors near the nucleus. The main conclusion of the work is that although the rate of mass transfer varies greatly over an individual cell, the average mass transfer rate to a cell is close to that predicted for a flat cell. In comparison to other hemodynamic factors, the topography of endothelial cells therefore seems to have little effect on mass transfer rates and is likely physiologically insignificant.