Early treatment with deferoxamine limits myocardial ischemic/reperfusion injury.
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)
Reddy
B R
BR
Division of Cardiology, Harper Hospital, Detroit, Michigan.
Kloner
R A
RA
Przyklenk
K
K
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels; D003676:Deferoxamine / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D007501:Iron / Q000652:urine; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*
D007501:Iron; D003676:Deferoxamine