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 Fe(3+)-HQ complex labeled with 59Fe was avidly taken up by isolated perfused hearts contrary to the hydrophilic complex Fe(3+)-citrate. Hearts perfused in aerobic conditions with Krebs-Henseleit buffer were exposed for 15 min to the iron complexes, Fe(3+)-HQ (5 microM/10 microM and 10 microM/20 microM), or Fe(3+)-citrate (10 microM), and then perfused for 30 min with normal buffer. Exposure to the high dose of Fe(3+)-HQ (10 microM/20 microM) 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 Fe(3+)-HQ (5 microM/10 microM) mimicked with a lower magnitude the effects of the high dose, whereas Fe(3+)-citrate had no effects on cardiac parameters. Only hearts exposed to the high dose of Fe(3+)-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 mM) in the perfusate. An immediate and high increase (x6) was seen during heart exposure to Fe(3+)-HQ (10 microM/20 microM) and to Fe(3+)-citrate (10 microM). Considering Fe(3+)-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 Fe(3+)-HQ-induced cardiac dysfunction. These results demonstrate the deleterious effect of increasing intracellular reactive iron level in non-ischemic hearts.