Myocardial tissue iron delocalization and evidence for lipid peroxidation after two hours of ischemia

Ischemic tissue injury has been proposed to be in part due to oxygen-radical-mediated lipid peroxidation. In vitro studies of such reactions show that they are thermodynamically unfavorable unless catalyzed by transitional metals such as iron in low molecular weight species (LMWS iron), ie, the iron-ADP complex. This study tests for iron delocalization into a LMWS pool during myocardial ischemia and for increased tissue malondialdehyde (MDA), a product of lipid peroxidation. Anesthesia was induced in eight dogs (weighing 20 to 30 kg) with ketamine and maintained by ventilation with 1% halothane. The left anterior descending coronary artery was ligated in four animals, and the circumflex coronary artery was ligated in the other four. Two hours after ligation, the animals were sacrificed by a central venous injection of KCl. Tissue samples were immediately taken from the ischemic zone and from the corresponding nonischemic zone. MDA was determined by the thiobarbituric acid assay. LMWS iron was determined on a tissue ultrafiltrate by the o-phenanthroline assay. Statistical data analysis used the matched-pair two-tailed t test. LMWS iron was 18.3 nM/100 mg in ischemic tissue versus 13.1 nM/100 mg in nonischemic tissue (t = 4.14; P < .01). MDA was 0.91 nM/100 mg in ischemic tissue versus 0.83 nM/100 mg in nonischemic tissue (t = 7.27; P < .005). We conclude that there is a significant increase in tissue LMWS iron and in MDA after two hours of regional myocardial ischemia. This iron might be the catalyst for maturation of tissue injury during reperfusion as observed by other investigators. Therapeutic iron chelators such as desferoxamine should be examined for tissue protection during reperfusion following ischemia.