Deferoxamine pretreatment reduces canine infarct size and oxidative injury.
To test whether iron-catalyzed processes contribute to myocardial necrosis during ischemia and reperfusion, we administered the iron chelator, deferoxamine, to chloralose-anesthetized dogs subjected to 90 min of left anterior descending artery occlusion followed by 360 min of reperfusion. Deferoxamine blocks iron-catalyzed hydroxyl radical formation in vitro. Groups of dogs received either pretreatment with deferoxamine or iron-loaded deferoxamine (15 mg/kg over 30 min preocclusion and 2.5 mg/kg/hr during the first 120 min of reperfusion), equal volumes of saline or deferoxamine treatment during reperfusion (15 mg/kg over 30 min beginning at 75 min of occlusion followed by 2.5 mg/kg/hr during the remainder of the first 120 min of reperfusion). Infarct size as a percentage of area at risk was reduced (P less than .05) by deferoxamine pretreatment (29.8 +/- 4.8%, n = 7, +/- S.E.) compared to saline control (46.8 +/- 4.7%, n = 8), deferoxamine reperfusion (50.5 +/- 6.7%, n = 8) or iron-loaded deferoxamine (60.2 +/- 8.6%, n = 3)-treated dogs. Deferoxamine pretreatment also decreased (P less than .05) the release of oxidized glutathione into the coronary sinus during early reperfusion compared to the other groups. There were no differences between groups in area at risk, risk zone blood flow during ischemia or in heart rate-blood pressure product. Deferoxamine did not decrease hydrogen peroxide concentration, neutrophil superoxide anion production or neutrophil adherence in vitro. We conclude that iron-mediated processes, possibly including iron-catalyzed hydroxyl radical formation, contribute to myocardial necrosis during regional ischemia and reperfusion.
Lesnefsky
E J
EJ
Division of Cardiology, University of Colorado Health Sciences Center, Denver.
Repine
J E
JE
Horwitz
L D
LD
D000818:Animals; D003327:Coronary Disease / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004285:Dogs; D005978:Glutathione / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D013482:Superoxide Dismutase / Q000378:metabolism
D013482:Superoxide Dismutase; D005978:Glutathione; D003676:Deferoxamine