Effect of iron overload in the isolated ischemic and reperfused rat heart

Summary It has been suggested that iron might play a pivotal role in the development of reperfusion-induced cellular injury through the activation of oxygen free radical producing reactions. The present study examined the effects of myocardial iron overload on cardiac vulnerability to ischemia and reperfusion. Moreover, the effect of the iron chelator deferoxamine in reversing ischemia-reperfusion injury was studied. Animals were treated with iron dextran solution (i.m. injection, 25 mg every third day during a 5 week period). The control group received the same treatment without iron. Isolated rat hearts were perfused at constant flow (11 ml/min) and subjected to a 15 minute period of global normothermic ischemia followed by reperfusion for 15 minutes. The effects of iron overload were investigated using functional and biochemical parameters, as well as ultrastructural characteristics of the ischemic-reperfused myocardium compared with placebo values. The results suggest that (a) a significant iron overload was obtained in plasma and hepatic and cardiac tissues (×2.5, ×16, and ×8, respectively) after chronic intramuscular administration of iron dextran (25 mg); (b) during normoxia, iron overload was associated with a slight reduction in cardiac function and an increase in lactate dehydrogenase (LDH) release (×1.5); (c) upon reperfusion, functional recovery was similar whether the heart had been subjected to iron overload or not. However, in the control group left ventricular end-diastolic pressure remained higher than in preischemic conditions, an effect that was not observed in the iron-overloaded group. Moreover, LDH release was markedly increased in the iron-loaded group (×4.2); (d) iron overload was associated with a significant worsening of the structural alterations observed during reperfusion, particularly at the mitochondrial and sarcomere level; (e) after 15 minutes of reperfusion, the activity of the anti-free-radical enzyme, glutathione peroxidase (GPX), was significantly reduced in ironoverloaded hearts, whereas catalase activity was increased; (e) the overall modifications observed in the presence of iron overload were prevented by deferoxamine. In conclusion, this study underlines the possible role of cardiac iron in the development of injury associated with ischemia and reperfusion, and the possible importance of the use of an iron-chelating agent in antiischemic therapy.