Effect of Iron Chelation on Myocardial Infarct Size and Oxidative Stress in ST-Elevation-Myocardial Infarction

Background-Experimental studies suggest that deferoxamine (DFO) limits the generation of reactive oxygen species by chelating redox-active iron and thereby may reduce ischemia-reperfusion injury and myocardial infarct (MI) size. We investigated whether DFO administered before reperfusion by primary percutaneous coronary intervention (PPCI) would ameliorate oxidative stress and MI size. Methods and Results-We randomly assigned 60 patients with ST-elevation-MI to receive an intravenous bolus of DFO (500 mg) immediately before PPCI followed by a 12-hour infusion (50 mg/kg of body weight) (n=28) or normal saline bolus and infusion (placebo group, n=32). MI size was measured by contrast-enhanced cardiac MRI (CMRI; day 3 +/- 1), creatine kinase and troponin I area-under-the-curve, and severity of wall motion abnormality on echocardiography. Clinical follow-up including repeat CMRI and echocardiography were performed at 3 months (100 +/- 17 days). Oxidative stress was assessed by plasma F-2-isoprostane levels. DFO and placebo groups were well balanced with respect to baseline characteristics, symptom- and door-to-balloon times, pre-PPCI coronary patency, and infarct-related artery location. Serum iron levels were decreased with DFO treatment after PPCI compared with placebo (3.0 +/- 2.5 versus 12.6 +/- 5.5 mu mol/L, P<0.0001), which persisted until the end of the infusion. In DFO-treated patients, there was a significant reduction in plasma F-2-isoprostane levels immediately after PPCI (2878 +/- 1461 versus 2213 +/- 579 pmol/L, P=0.04). However, there was no difference in CMRI-determined infarct size (DFO, 17.4 +/- 10.8%, versus placebo, 18.6 +/- 10.2%; P=0.73), myocardial salvage index at 3 days or at 3 months, or the area-under-the-curve for creatine kinase or troponin I. Conclusions-Adjunctive DFO treatment after the onset of ischemia and continued periprocedurally ameliorates oxidative stress without limiting infarct size. Clinical Trial Registration-URL: http://www.anzctr.org.au/. Unique identifier: ACTRN12608000308392. (Circ Cardiovasc Interv. 2012;5:270-278.)