Apocynin exerts dose-dependent cardioprotective effects by attenuating reactive oxygen species (ROS) in ischemia/reperfusion (I/R)

I/R results in cardiac contractile dysfunction in part due to increased ROS and decreased endothelial-derived nitric oxide (NO) release. Thus, inhibiting NADPH oxidase and subsequent ROS release with apocynin may preserve cardiac function and reduce infarct size following I/R. In isolated rat hearts following I (30 min)/R (45 min), apocynin given at reperfusion significantly restored left ventricular developed pressure (LVDP) dose-dependently by 57 ± 9% (40 μM, n=7) and 82 ± 5% (400 μM, n=9) (p<0.01) of baseline respectively, at 45 min postreperfusion compared to untreated control I/R hearts (n=9) that recovered to 46 ± 7% (n=9) of baseline values for LVDP. The dose-dependent effect of apocynin on LVDP was also associated with a significant decrease in infarct size compared to untreated I/R hearts (p<0.05). To test whether these effects were caused by apocynin-induced reduction in hydrogen peroxide (H 2 O 2 , index of ROS) and increased NO release, we studied ROS in real-time in vivo during femoral artery/vein I/R. Apocynin (14 mg/kg, given i.v. at reperfusion, n=6) significantly decreased H 2 O 2  and increased endothelial-derived NO release in femoral I/R from 20 to 45 min postreperfusion compared to saline controls (n=7) (p<0.01). These results suggest that apocynin attenuates I/R-induced cardiac contractile dysfunction and infarct size by inhibiting ROS release from NADPH oxidase in reperfused tissues.