Date of Award

2013

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Lindon Young, PhD

Second Advisor

Robert Barsotti, PhD

Third Advisor

Ruth Borghaei, PhD

Fourth Advisor

Marcus G Bell, PhD

Abstract

Reactive oxygen species (ROS) generated during myocardial I/R contribute to post-reperfused cardiac contractile dysfunction. Damaged cardiomyocyte mitochondria are major sites of excess ROS generation during reperfusion. We hypothesized that reducing mitochondrial ROS formation should attenuate myocardial I/R injury and thereby improve function of isolated perfused rat hearts subjected to I(30min)/R(45min) compared to untreated I/R hearts. Mitoquinone (MitoQ, MW=579g/mol; complexed with cyclodextrin (MW=1135g/mol) to improve water solubility, total MW=1714g/mol), a coenzyme Q derivative, and SS-31 (Szeto-Schiller) peptide ((D-Arg)-Dmt-Lys-Phe-Amide, MW=639g/mol, Genemed Synthesis, Inc., San Antonio, TX), an alternating cationic-aromatic peptide, are selective mitochondrial ROS inhibitors which significantly improved post-reperfused cardiac function compared to untreated I/R controls in this study (p

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