Cardiovascular tissue remodeling at multiple length scales
Creators: name: Bellini, Chiara
Publisher: name: University of Calgary
Year: 2012

description: Bibliography: p. 192-200
description: Some pages are in colour.
description: Includes copy of animal protocol approval and copyright permissions. Original copies with original Partial Copyright Licence.
description: The human body is a biological system composed of elements organized into levels of increasing complexity. A common rule seems to hold true across length scales, which relates the structure of biological systems with the function they perform. Stimuli of different origin may create imbalances in the structure-function relationship and promote a growth and remodeling cascade to restore preferred form and function (homeostatic condition). Clinical relevance of remodeling studies stems from the in­terpretation of many diseases as the result of an adverse remodeling process. In this thesis different aspects of the remodeling process that occurs in the cardiovascular system will be analyzed at three levels of magnification: organ, tissue and microstruc­tural components. The effect of atrial fibrillation on left atrium mechanics was investigated at the or­gan and tissue levels. Dynamic CT scans were used to generate a computational model of the porcine left atrium, which was not limited to the organ itself but also included fine anatomical features of the structures that guide and constraint its movement throughout the cardiac cycle, such as pericardium, pulmonary veins and mitral valve annulus. Computational results seem to suggest that a stress-mediated mechanism contributes to the onset and progression of atrial fibrillation. The regional mechanical behavior of tissues in the atria was assessed on excised specimens by means of planar biaxial tests, while polarized light microscopy was used to determine the dominant orientation of cardiomyocytes. Mechanical and microscopy measurements were then combined to fit constitutive relationships consistent with the microstructure. The development of atrial fibrillation was documented to promote stiffening of the me­chanical response and thickening of the wall, both effects contributing to decrease tissue deformability. Finally, the contribution of microstructural constituents ( collagen fibers, elastic material and smooth muscle cells) in supporting the mechanical loads applied to the wall of large, conduit arteries was investigated. Pressure-diameter tests were per­formed on murine carotid arteries from wild-type and genetically-modified mice to record the tissue mechanical response. Histological assays were used to evaluate the relative abundance of constituents in the vascular wall. A structurally-motivated con­stitutive relationship was fitted to the mechanical data and fed to a numerical model, which was able to predict the redistribution of stresses among the main components of the arterial tissue in response to a perturbation of the external loads. The pro­posed model can be used to assess how the microstructural reorganization associated with the progression of specific diseases affects the mechanical loads supported by individual constituents.