Effects of Increasing Intracellular Reactive Iron Level on Cardiac Function and Oxidative Injury in the Isolated Rat Heart

Elevation of cell iron content was produced by use of a lipophilic iron ligand, 8-hydroxyquinoline (HQ), capable of transferring catalytically active iron into cells. The Fe3+-HQ complex labeled with59Fe was avidly taken up by isolated perfused hearts contrary to the hydrophilic complex Fe3+-citrate. Hearts perfused in aerobic conditions with Krebs–Henseleit buffer were exposed for 15 min to the iron complexes, Fe3+-HQ (5μ /10μ and 10μ /20μ ), or Fe3+-citrate (10μ ), and then perfused for 30 min with normal buffer. Exposure to the high dose of Fe3+-HQ (10μ /20μ ) resulted in early and irreversible decreases in coronary flow and heart rate (−48% and −33%, respectively), initial increases followed by decreases in left ventricular systolic pressure and +dP/dt, and increase in left ventricular end-diastolic pressure (+80%). The low dose of Fe3+-HQ (5μ /10μ ) mimicked with a lower magnitude the effects of the high dose, whereas Fe3+-citrate had no effects on cardiac parameters. Only hearts exposed to the high dose of Fe3+-HQ exhibited a significant increase (+60%) in thiobarbituric acid-reactive substance level, an index of lipid peroxidation. The production of hydroxyl radicals was investigated by measuring 2,3-dihydroxybenzoic acid level in the coronary effluent after addition of salicylic acid (1 m ) in the perfusate. An immediate and high increase (×6) was seen during heart exposure to Fe3+-HQ (10μ /20μ ) and to Fe3+-citrate (10μ ). Considering Fe3+-citrate had no effect on cardiac function and lipid peroxidation it was concluded that this hydroxyl radical formation occurring in the extracellular space was not implicated in Fe3+-HQ-induced cardiac dysfunction. These results demonstrate the deleterious effect of increasing intracellular reactive iron level in non-ischemic hearts.