An Ovine Model of Dilated Cardiomyopathy Induced by Doxorubicin

Dilated cardiomyopathy is associated with a progressive deterioration in cardiac function and eventually death. Initial interest in this hypothesis was to create another large animal model for dilated cardiomyopathy in addition to pigs and dogs. After the induction of anesthesia to 10 female sheep, a carotid-jugular shunt was created in all the animals via a 1-cm fistula between the carotid artery and jugular vein. Six sheep out of the total of 10, were given intravenous Doxorubicin. Echocardiographic studies were performed before surgery and 3 months after that. The 4 animals not injected with Doxorubicin were evaluated for echocardiographic parameters after one year. There was no abnormality in echo parameters in the 4 sheep that had not received Doxorubicin; in addition, their valves and cardiac output were normal. As regards the six sheep injected with Doxorubicin, 4 received a dose of 2 mg/kg weekly and expired after the second injection due to the toxicity of the drug, 1 was given Doxorubicin 1 mg/kg and died after one week, and 1 had Doxorubicin 0.5 mg/kg but showed no abnormality in terms of dilated cardiomyopathy. We conclude that the sheep is sensitive to Doxorubicin and that the dosage that is enough for creating dilated cardiomyopathy in dogs is very toxic for the sheep.