An Ovine Model of Dilated Cardiomyopathy Induced by Doxorubicin

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.