Graduation Date

Summer 8-13-2021

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Matthew C. Zimmerman PhD

Second Advisor

Ted Mikuls MD

Third Advisor

Stephen Mathai MD

Fourth Advisor

Bunny Pozehl PhD

Abstract

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disease, which is progressive and fatal despite advances in therapy. Animal models have shown that oxidative stress may be pathogenic in PAH. We hypothesize that oxidative stress, as measured by increased levels of a specific reactive oxygen species, superoxide (O2•-), mayplay a role in PAH in humans. Using a novel application of electron paramagnetic resonance (EPR) spectroscopy, we initially evaluated whether levels of O2•- from whole blood collected from the pulmonary artery collected during right heart catheterization (RHC) would correlate with O2•- levels in peripheral venous blood. There was a significant correlation. We then measured O2•- in peripheral venous blood in patients with PAH and normal controls. We hypothesized that O2•- as a measure of oxidative stress would be elevated in patients with PAH compared with normal controls and that O2•- levels would correlate with measures of PAH severity. Results showed no significant elevation of O2•- levels in PAH patients versus controls. Furthermore, there were no correlations between levels of O2•- and severity of PAH. Contrary to previous animal studies and indirect measures of oxidative stress, we were unable to confirm an oxidative environment in PAH, at least when assessed by whole blood O2•- levels measured by EPR spectroscopy.

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