Date of Award

Spring 2004

Document Type

Thesis - Restricted

Degree Name

Master of Science (MS)

Department

Biomedical Engineering

First Advisor

Audi, Said

Second Advisor

Krenz, Gary

Third Advisor

Olson, Lars

Abstract

This thesis investigates changes in the redox status of the pulmonary endothelium in lungs from rats exposed to chronic hyperoxia as a model of oxidative stress. The thiazine compound Toluidine Blue 0 (TBO) is used as a probe in the multiple indicator dilution (MID) method to evaluate changes in the activity of the pulmonary endothelium transplasma membrane electron transport system (TPMET) in response to hyperoxia. TPMET, which transport electrons from int racellular electron donors to extracellular electron acceptors is a key component of the pulmonary endothelium redox system, and its activity is potentially affected by changes in the redox status of the pulmonary endothelium resulting from chronic exposure to hyperoxia. A mathematical model is used to quantitatively interpret the measured MID data. Results indicate an increase in the activity of pulmonary endothelium TPMET activity over the course of hyperoxic exposure consistent with a potential role for TPMET in lung adaptation to hyperoxia as a model of oxidative stress. Chapter 1 presents relevant introduction information. Chapter 2 describes the methods that were used to condition the rats set up the experiments, and collect data. Chapter 3 summarizes the data that was collected for each experiment. Chapter 4 describes the identification of model parameters and the development of the mathematical model used to interpret the data. Chapter 5 presents the model results. Chapter 6 discusses the findings of the collected data and the model results. This chapter makes comparisons to results published from related studies and draws conclusions about this study. Appendix A provides a more detailed derivation of the model presented in Chapter 4. Appendices B through F provide content that may serve as a manual for using the photodetector system and setting up the experiments related to this study; they augment the methods described in Chapter 2. Appendix G is a listing of the Matlab scripts and C code used to analyze the data.

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