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 of 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 +/- 2.5 micrograms in control, pretreated, and
deferoxamine at reperfusion groups respectively; p less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)