This research project is designed to establish the technical merit and feasibility of commercial production of rats with the cardiomyopathy of iron overload. Pilot studies have shown that cardiac iron deposition near the magnitude associated with arrhythmias and congestive heart failure in patients with iron overload can be produced in rats. Iron loading of the heart required at least four months of daily feeding of a specially formulated, iron- supplemented liquid diet to rats with a portacaval shunt. During the proposed project, rats with a portacaval shunt will be fed liquid, iron- supplemented diets for four months in the animal facilities of Zivic- Miller Laboratories. For the final two months of the study, the animals will be transferred to the animal facilities at Case Western Reserve University where serial echocardiography will be used to monitor cardiac function. At autopsy, detailed pathological and biochemical studies of the heart will be performed. A commercially available animal model of the cardiomyopathy of iron overload would provide a new means of: (i) examining the pathophysiologic mechanisms responsible for iron-related cardiac toxicity, and (ii) evaluating the potential therapeutic usefulness of recently developed, orally active iron-chelating agents in reversing or preventing myocardial damage in patients with transfusional iron overload.
| Brittenham, G M (1994) New advances in iron metabolism, iron deficiency, and iron overload. Curr Opin Hematol 1:101-6 |
