Modeling the Structural and Mechanical Properties of Pulmonary Arteries in an Animal Model of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated mean pulmonary arterial pressure. Although the cause of the disease onset is unclear, manifestations such as remodeling and occlusion of the distal pulmonary arteries lead to pressure overload of the right ventricle, eventually leading to heart failure. While much research has focused on the remodeling of smooth muscle and endothelial cells in the pulmonary arteries, collagen extracellular matrix changes in structure and function are not well defined. In this thesis, mechanical and microstructural properties of pulmonary arteries were investigated during the progression of PAH. Results indicated that the axial and circumferential directions to not respond the same to mechanical loading, collagen fibers become less tortuous and realign to a preferred direction, and left and right pulmonary arteries do not remodel identically. Five models of the pulmonary arterial mechanics were developed to determine the role of structural features in the vascular mechanical response found with biaxial tubular testing of vessels in a rat model of PAH. Models included families of fibers, viscoelasticity, and elasticity theory. While the viscoelasticity-based model was able to identify the changes in the vessel stiffness, it did not account for the structural changes undergone by the vessel. On the other hand, the fiber-family models were able to incorporate collagen fiber preferred directions but were either over-parameterized and or did not account for tortuosity and collagen diameter changes. The elasticity-based model was found to fit measured data, and identify differences in the modulus of elasticity found in circumferential and axial directional data. Future iterations of the model should include measurements such as individual fiber diameter, data from fibers throughout the vessel, or contributions from other vessel constituents such as elastin fibers