Periodic
blood transfusion can lead to secondary
iron overload in patients with hematologic and oncologic diseases.
Iron overload can result in
iron deposition in heart tissue, which decreases cardiac function and can ultimately lead to death due to
dilated cardiomyopathy and
cardiac failure. In this study, we established murine model of secondary
iron overload, studied the changes in cardiac function with echocardiography, and examined the histopathologic changes. Three experimental groups of the six week-old C57/BL mice (H-2(b)) were injected intraperitoneally with 10 mg of
iron dextran daily 5 days a week for 2, 4, and 6 weeks. Cumulative doses of
iron for the three experimental groups were 100, 200, and 300 mg, while the control groups were injected with the same amounts of
phosphate-buffered saline. We studied the cardiac function under
anesthesia with echocardiography using a GE Vivid7 Dimension system. Plasma
iron levels and liver
iron contents were measured. The hearts and livers were harvested and stained with H&E and Perls
Prussian blue for
iron, and the levels of
iron deposit were examined. We assessed the cardiac measurements after adjustment for weight. On echocardiography, thicknesses of the interventricular septum and posterior ventricular wall (PS) during diastole showed correlation with the amount of
iron deposit (P < 0.01). End-diastolic volume showed dilatation of the left ventricle in the 300 mg group (P < 0.01). Changes in the fractional shortening were not statistically significant (P = 0.07). Plasma
iron levels and liver
iron contents were increased proportionally according to the amount of
iron loaded. The histopathologic findings of PS and liver showed higher grade of
iron deposit proportional to the cumulated
iron dose. In this study, we present an animal model which helps understand the cardiac function changes in patients with secondary
iron overload due to repeated
blood transfusions. Our results may help characterize the pathophysiologic features of
cardiomyopathy in patients with secondary
iron overload, and our model may be applied to in vivo
iron-chelating
therapy studies.