Abstract |
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.
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Authors | Nathan L Lubbers, James S Polakowski, James D Crapo, Craig D Wegner, Bryan F Cox |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 41
Issue 5
Pg. 714-9
(May 2003)
ISSN: 0160-2446 [Print] United States |
PMID | 12717101
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Metalloporphyrins
- manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin
- Superoxide Dismutase
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Topics |
- Animals
- Dose-Response Relationship, Drug
- Hemodynamics
(drug effects)
- Male
- Metalloporphyrins
(administration & dosage, chemistry, pharmacology)
- Molecular Mimicry
- Myocardial Infarction
(drug therapy, etiology, pathology)
- Myocardial Ischemia
(complications)
- Myocardial Reperfusion Injury
(drug therapy, etiology)
- Rats
- Rats, Sprague-Dawley
- Superoxide Dismutase
(chemistry)
- Time Factors
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