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.
Lubbers
Nathan L
NL
Integrative Pharmacology, Global Pharmaceutical Discovery, Abbott Laboratories, Abbott Park, Illinois, USA.
Polakowski
James S
JS
Crapo
James D
JD
Wegner
Craig D
CD
Cox
Bryan F
BF
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D018716:Molecular Mimicry; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000737:chemistry; D013997:Time Factors
D008665:Metalloporphyrins; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin; D013482:Superoxide Dismutase