Arterial remodeling using a constituent-based approach

This thesis is intended to contribute to the field of biomechanics of growth and remodeling of arteries. The work focuses particularly on growth and remodeling caused by sustained hypertension, increased blood flow, and ageing. A structure-based constitutive law is employed, which accounts for the elastic and structural properties of the components of the vascular tissue. Analysis of the biomechanical properties of the arterial wall allows for quantification of the developed wall stresses and strains. The dynamics of arterial growth and remodeling is described by appropriate remodeling rate equations. The corner-stone of this theoretical project is, of course, the development of physiologically relevant evolution laws describing the shear stress- and wall stress-induced growth and remodeling of the arterial wall. The model predictions are presented in the form of an introduction, four chapters (four papers) and a conclusion. The introduction begins with the motivation for this project. The link between mechanical load and remodeling in blood vessels follows. The state of the art on theoretical models of arterial remodeling in response to hypertension, changed flow, and ageing is also presented. The first paper presents a novel theoretical model of hypertension-induced arterial remodeling using a structure-based constitutive law. Arterial remodeling in response to sustained hypertension has been previously modeled using a phenomenological strain energy function (SEF), the parameters of which do not bear a clear physiological meaning. Here, we extend the work of Rachev et al. by applying similar evolution laws to a constituent-based SEF, which includes a statistical description for collagen recruitment in load bearing. Remodeling affects the material properties only through changes in the probability density function of collagen engagement. The model simulates the remodeling of a rabbit thoracic aorta and predicts that, at the final adapted hypertensive state, the wall thickness is increased to conserve the baseline value of hoop stress and the lumen radius remains unchanged to preserve the normotensive levels of intimal shear stress. Furthermore, the remodeling of material properties serves to restore the arterial compliance to control levels. The material at the final adapted state is softer than its normotensive counterpart as indicated by the average circumferential stress-strain curves. Model predictions are in good qualitative agreement with experimental data. The novelty in our findings is that biomechanical adaptation leading to maintenance of compliance at the hypertensive state can be perfectly achieved by appropriate readjustment of the collagen engagement profile alone. The second paper addresses a predictive model of arterial remodeling in response to increased flow using a constituent-based SEF. Prior theoretical models of arterial remodeling in response to changes in blood flow were based on the assumption that material properties of