Combinatorial Effects of Apocynin (apo) and Mitoquinone (mitoQ) in Treatment of Myocardia Ischemia/Reperfusion (MI/R) Injury

Date of Award


Degree Type


Degree Name

Master of Science (MS)

First Advisor

Lindon Young, PhD

Second Advisor

Ruth Borghaei, PhD

Third Advisor

Robert Barsotti, PhD

Fourth Advisor

Marcus G Bell, PhD


Reactive oxygen species (ROS) are generated due to the influx of oxygen during myocardial ischemia/ reperfusion (MI/R) injury and contributes to post-reperfused cardiac contractile dysfunction and increased infarct size. Damaged mitochondria and NADPH oxidase activation are major sites of ROS in MI/R. Prior studies have reported that either apocynin, a NADPH oxidase inhibitor, or mitoQ, a mitochondrial-targeted antioxidant, dose-dependently improved post-reperfused left ventricular developed pressure (L VDP) and reduced infarct size in isolated (ex-vivo) rat hearts subjected to I(30min)/ R(45min). This led to question whether sub- effective doses of apocynin and mitoQ given together can act synergistically to improve post-reperfused L VDP and reduce infarct size compared to either drug alone or control. Data from this study show that the combination of apo ( 40µM) + mitoQ (1 µM) (n=8) significantly reduced infarct size to 29 ± 3% compared to control IIR hearts (pand mitoQ I µM (51± 10% and 53± 8% of baseline), respectively. Collectively, the data suggests that the combination of sub-effective doses of apocynin + mitoQ acted additively/ synergistically reduce infarct size and improve some post-reperfused cardiac function parameters respectively.

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