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

Abstract

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 μmol/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.

Comparative Study of Elemental Concentrations in the Scalp Hair and Nails of Myocardial Infarction Patients Versus Controls from Pakistan

“…Redox-active iron released from macrophages and intracellular myocyte stores is capable of catalyzing reactive oxygen species (ROS) production via Fenton chemistry to generate potent oxidants (including the highly reactive hydroxyl radical) that participate in lipid peroxidation and cellular injury. The results of present study were consistent with the other reports in which Fe concentrations were higher in MI patients than those of controls [20,21]. Among others, Bnovel^bio-chemical risk factors for cardiovascular diseases include endothelial dysfunction, increased carotid intima-media thickness (IMT), and increased arterial stiffness.…”

“…PC 2 showed significant loadings for Fe, Cr, and Cd which were mainly contributed by anthropogenic activities. Interestingly, some of these elements are involved in the production of reactive oxygen species (ROS), which oxidizes the low density lipoprotein (LDL), a well-known inducer of heart attack [21,29], thus pointing out their mutual role in the disease. In the case of controls, PC 1 showed elevated loadings for Na, K, Sr, and Zn, while second PC exhibited higher loadings for Ca, Mg, Fe, and Mn, which were predominantly associated with the dietary intake and food habits of the donors.…”

Protective effect of glycyrrhizin on myocardial ischemia/reperfusion injury-induced oxidative stress, inducible nitric oxide synthase and inflammatory reactions through high-mobility group box 1 and mitogen-activated protein kinase expression

“…Infusion of hemameba into the heart with isolated perfusion has been demonstrated to result in I/R (20). These findings support the theory that neutrophil granulocytes have pathogenic effects in myocardial I/R injury (21).…”

Transdermal deferoxamine prevents pressure-induced diabetic ulcers

“…In ischemic tissues, DFO is known to reduce levels of reactive oxygen species (ROS), which play a major role in diabetic ulcer pathogenesis and persistence (40,41). Therefore, we evaluated the influence of transdermal DFO treatment on superoxide levels using DHE immunofluorescent staining (42).…”