Date of Award

Spring 2010

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Mechanical Engineering

First Advisor

Robin Shandas

Second Advisor

Hang J. Qi

Third Advisor

Kendall S. Hunter

Abstract

Pulmonary hypertension (PH) is characterized by chronic high blood pressure in the pulmonary arteries (PAs) and is an important cause of morbidity and mortality in children and adults. During the development of PH, the pulmonary circulation displays significant arterial remodeling, which yields changes in mechanical behavior and subsequently, of pulmonary vascular function (PVF). Recent clinical findings suggest that knowing the change in PVF is important for accurate prognosis of PH and its severity, and may be relevant in developing treatment strategies. One clinical effort has focused on the measurement of pulmonary vascular input impedance, which can provide comprehensive characterization of PH and the mechanical properties and behavior of proximal PAs; these properties strongly affect the impedance and right ventricular afterload. In this dissertation, the measurement uncertainty in the pulmonary vascular input impedance estimated from pulsed-wave Doppler-measured velocity and pressure measurements is examined to provide the guidance for the use of impedance in clinical studies. To examine the mechanical properties of proximal PAs, in vitro studies on the arterial remodeling including mechanical and histological aspects due to chronic hypoxia in the proximal PAs of both adult rat and neonatal calf models of PH are performed to seek mechanobiological relation of the proximal PAs. Combining in vitro and in vivo arterial geometry data from main PA (MPA) of neonatal calves, the in vivo stretch distribution and collagen engagement in MPAs are examined and the impact of residual stretch and arterial remodeling is then investigated. Finally, an approach is proposed to quantify the appropriateness of constitutive models for proximal PAs by comparing the predicted and measured pressure-diameter curves in calf MPAs. With the constitutive model, the relation between the collagen contribution to the pressure loading at the physiological conditions and the PH disease state can be established, and such concept can be applied to clinical studies for the diagnosis of PH. Overall, these investigations of PVF in PH from in vivo, in vitro and modeling studies can provide a better understanding of functional changes of the entire pulmonary circulation, which in turn will be useful to the diagnosis and treatment of PH.

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