Date of Award

2008

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology

Supervisor

Dr. Fred Possmayer

Second Advisor

Dr. Chris Ellis

Third Advisor

Dr. Barry Tepperman

Abstract

The mechanisms by which mechanical ventilation (MV) contributes to the progression of ventilator-induced lung injury (VILI) were investigated in adult rats. The first study in this thesis investigated the physiologie consequences of early surfactant alterations during MV. It was hypothesized that surfactant alterations induced by MV contribute to physiologie dysfunction. The second study investigated the specific role of increased levels of cholesterol observed in VILI in the biophysical dysfunction of surfactant. It was hypothesized that cholesterol significantly inhibits surfactant function in VILI. Early surfactant alterations contributed to physiologie dysfunction that could be mitigated by restoring functional surfactant pools. Surfactant obtained in the late stages of VILI exhibited increased levels of cholesterol that were shown to be highly inhibitory to surfactant function. It was concluded that early surfactant alterations contribute to physiologie dysfunction, and that an increase in the level of cholesterol is a major mechanism of surfactant dysfunction in VILI.

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