Combinational effects of apocynin and mitoquinone in reducing myocardial ischemia/ reperfusion injury (1080.7)

Abstract

Reactive oxygen species (ROS) is generated due to the influx of oxygen during MI/R 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. In prior studies, apo, a NADPH oxidase inhibitor, and mitoQ, a mitochondrial‐targeted antioxidant, dose‐dependently improved post‐reperfused left ventricular developed pressure (LVDP) and reduced infarct size in rat hearts subjected to I(30min)/R(45min). This led us to question whether low doses of apo and mitoQ given together can act synergistically to improve post‐reperfused LVDP and reduce infarct size compared to either drug alone or control? Early data shows that the combination of apo (40μM) + mitoQ (1 μM ) (n=7) reduced infarct size to 27 ± 11% compared to mitoQ (1 μM) (n= 6) 54 ± 6% (p<0.05); apo (40 μM) (n=6) 40 ± 8% and control I/R hearts (n=7) 42 ± 5%. Reduced infarct size of the apo + mitoQ combination correlated with an improvement in LVDP (61 ± 4% of baseline) compared to control hearts (44 ± 10% of baseline) and apo 40 μM and mitoQ 1 μM (58 ± 9% and 44 ± 12% of baseline), respectively. Although the combination reduced infarct size and improved post‐reperfused LVDP more so then either drug alone or control, at these concentrations the combinations did not act synergistically. Other combinations will be tested to further establish the dose‐dependent effects.