Early treatment with deferoxamine limits myocardial ischemic/reperfusion injury

B. Ramesh Reddy, Robert A. Kloner, Karin Przyklenk

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105 Scopus citations


Oxygen-derived free radicals (the superoxide anion O2- and hydroxyl radical ·OH) have been implicated in myocardial injury associated with coronary artery occlusion followed by reperfusion. Transition metals (such as iron or copper) are needed to catalyze the formation on the ·OH radical and subsequent ·OH-mediated lipid peroxidation, yet the role of these transition metals in the pathogenesis of myocyte necrosis remains undefined. To address this issue, 21 dogs underwent 2 h of coronary artery occlusion and 4 h of reperfusion. Each animal was randomly assigned into 1 of 3 treatment groups: 7 received the iron chelator deferoxamine beginning 30 min preocclusion, 7 received deferoxamine beginning 5 min prior to reperfusion, while 7 dogs served as saline controls. Deferoxamine effectively chelated free iron in both treatment groups (total urine iron content averaged 42 ± 16, 662 ± 177* and 803 ± 205* micrograms in control, pretreated, and deferoxamine at reperfusion groups respectively; * p < 0.05), but had no significant effect on in vivo area at risk (AR), hemodynamic parameters, collateral blood flow during occlusion, or myocardial blood flow following reperfusion. Area of necrosis (AN) in dogs pretreated with deferoxamine (34.6 ± 3.7%* of the AR; *p < 0.05) was significantly smaller than that observed in the saline control group (55.4 ± 4.7% of the AR). Deferoxamine administered at the time of reperfusion, however, had no significant effect on infarct size (AN/AR = 54.3 ± 8.7%, p = NS vs. controls). Thus, early treatment with the iron chelator deferoxamine acutely reduced the extent of myocyte necrosis produced by 2 h of transient coronary artery occlusion in the canine model. These data support the hypothesis that iron catalyzed production of oxygen derived free radicals contribute to myocyte necrosis in the setting of ischemia-reperfusion.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalFree Radical Biology and Medicine
Issue number1
StatePublished - 1989


  • Coronary occlusion
  • Free radicals
  • Myocardial infarct size
  • Oxygen free radicals
  • Reperfusion


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