Studies of Blood Flow in Arterial Bifurcations; from Influence of Hemodynamics on Endothelial Cell Response to Vessel Wall Mechanics

The pathology of arterial diseases such as aneurysms and atherosclerosis is of great clinical interest. Several decades have passed since attempts to correlate hemodynamic factors to pathology of these diseases began. Under the hypothesis that hemodynamics is an important factor responsible for arterial diseases, we attempt to (i) investigate geometrical risk factors responsible for aneurysm formation in arterial bifurcations, (ii) evaluate a current hypothesis that aneurysms develop as a result of purely inertial effects on pressure fields at bifurcations (iii) design a novel flow chamber which reproduces flow fields found at arterial bifurcations to study endothelial cell functions due to hemodynamic stresses and (iv) develop a small on large theory for modeling small periodic motions of arterial walls superposed on large deformations. An outcome of this work included the development of a new methodology for generating realistic idealized bifurcation models.A number of researchers have identified geometric features common to arterial bifurcations. Here, idealized models have been developed that contain all these geometric features. These idealized models are used to investigate effects of Re, radius of curvature and bifurcation angle on arterial bifurcations. Elevated pressure and wall shear stress at the apex of bifurcation, which could be responsible for aneurysm formation, are found to arise as the fluid is diverted into the two daughter branches. Careful modeling of the apex region of the bifurcation is found to be needed for study of aneurysm due the important role of radius of curvature. The bifurcation angle is found to have only minor influence on the stresses at the apex region. Through this analysis, we found that the elevated wall shear stress at the apex is likely an important risk factor responsible for the formation of aneurysms. Based on the results from the computational bifurcation study, a flow device was designed to test the response of endothelial cells to wall shear stresses found at arterial bifurcations. The function of endothelial cells responding to hemodynamic stresses are hypothesized to degrade arterial walls and in turn, possibly cause initiation of aneurysms. Through numerical and analytical studies, we successfully designed a novel flow chamber which has two flow regimes : one for testing the cells exposed to wall shear stresses found in straight arteries and the other found at arterial bifurcations. This second section recreates the quantitative and qualitative features of flow fields found at arterial bifurcations. In order to model blood and arterial wall interaction in studies of hemodynamic factors related to arterial diseases and aging, a constitutive model for the vessel wall is required. Based on multi-mechanism theory, the role of elastin and collagen fibers, responsible for the passive mechanical response of arteries, are included as separate mechanisms. This theory is then used with small on large theory which approximates large deformations as the superposition of a small deformation on a large deformation. Taking this approach, the prestretch and preloading of the vessel can be included. Since deformations due to oscillatory motions of arterial walls are reported to be small compared with deformations due to the preloadings, the small on large theory is appropriate. The novelty of this study was to (i) employ a nonlinear constitutive equation for the large deformation region, (ii) develop governing equations for the wall motion using a small on large theory and (iii) include the separate roles of elastin and collagen fibers in modeling vessel walls