Preischemic and Postischemic Administration of AEOL10113 Reduces Infarct Size in a Rat Model of Myocardial Ischemia and Reperfusion

Reactive oxygen species (ROS) have been implicated as important mediators of cellular damage during ischemia/reperfusion. AEOL10113 is a low-molecular-weight superoxide dismutase mimetic that has dismutase activity against ROS. The objective of this study was to test the cardioprotective efficacy of postischemic administration of AEOL10113 in a rat model of left ventricular ischemia and reperfusion. Left ventricular infarction was produced by 25 min of left coronary artery occlusion followed by 3 h of reperfusion. Infarct size (IS) is reported as IS/area at risk (AAR). The control group had an IS/AAR of 67.5 +/- 2.6%. Postischemic administration of AEOL10113 beginning 5 min prior to reperfusion at doses of 0.03, 0.1, and 0.3 mg/kg resulted in an IS/AAR of 69.3 +/- 3.4%, 57.8 +/- 3.3% (P < 0.05), and 55.0 +/- 2.9% (P < 0.05), respectively. Preischemic administration of AEOL10113 beginning 5 min prior to occlusion at a dose of 0.3 mg/kg resulted in an IS/AAR of 44.2 +/- 5.9% (P < 0.0125). AAR as a percentage of the left ventricle and rate-pressure product were unaffected by any dose tested. The data from this study demonstrate that pre- and postischemic administration of AEOL10113 reduces IS in a rat model of myocardial ischemia and reperfusion.