Failure of deferoxamine to reduce myocardial infarct size in a primate model of ischemia-reperfusion injury.
Baboons were subjected to treatment with deferoxamine (DF), a strong iron-chelating agent, to inhibit the iron-dependent production of hydroxyl radicals. Studies were then done to determine if this would result in a reduction in the size of myocardial infarct. Baboons underwent occlusion of the left anterior descending coronary artery for 2 hr followed by reperfusion for the next 22 hr. A treated group (n = 4) received a 2-hr preischemic intravenous infusion of DF (10 mg/kg/hr). This infusion continued throughout the ischemic phase and 2 hr into the reperfusion phase. A control group (n = 8) underwent the identical protocol minus the DF infusion. At the end of the reperfusion period, the hearts were sectioned and stained for histological examination. The treated animals had a 22% larger volume of infarct compared with those of the controls (P = 0.06). There was no statistically significant difference (P > 0.05) in hemodynamic or epicardial ST segment measurements between the two groups. In this primate model, there was no myocardial protection afforded by DF. Baboons are similar to humans in that both have minimal collateral circulation. In the literature, DF has been noted to actually contribute to the production of free radicals in certain circumstances. This experiment appears to indicate that caution should be exercised in the use of DF in the treatment of ischemia-reperfusion injury of the heart.
Watanabe
B I
BI
Cardiovascular Research Laboratory, Queens Medical Center, Honolulu, Hawaii 96813.
Limm
W
W
Suehiro
A
A
Suehiro
G
G
Premaratne
S
S
McNamara
J J
JJ
D000818:Animals; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D005609:Free Radicals; D017665:Hydroxyl Radical / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010215:Papio
D005609:Free Radicals; D017665:Hydroxyl Radical; D003676:Deferoxamine