Induction of chronic cardiac insufficiency by arteriovenous fistula and doxorubicin administration.
OBJECTIVE
Large animal experimental models of chronic heart failure (HF) permit repeated invasive assessment of cardiovascular function, and evaluation of new medical or surgical therapies. The existing models however fail to achieve stable and long-term HF. The aim of this study was to create a simple and stable chronic model of HF in goat, using both arteriovenous fistula and weekly intravenous doxorubicin injections.


METHODS
After a preliminary experiment on four goats receiving weekly 1 to 2 mg/kg of doxorubicin, six adult female goats, having had an arteriovenous fistula without signs or symptoms of heart failure, received weekly two different dosages of doxorubicin for 13 weeks: group A (n = 3) received 0.5 mg/kg and group B (n = 3) received 1 mg/kg. After a three-month period without medication, both groups received again 1 mg/kg for four weeks. Cardiac function was assessed by repeated electrocardiographic and echocardiographic examinations.


RESULTS
Four goats died during the medication period (one in group A, three in group B). During the period without medication a stable ventricular hypocontractility with left ventricular dilation was observed. Left ventricular dysfunction was more pronounced in group B, and was associated with clinical symptoms of HF.


CONCLUSIONS
Arteriovenous fistula alone did not produce HF. Its association with doxorubicin injections provides a simple and stable chronic model of HF. This association allows reduction of the required doxorubicin dose and toxicity in animals and in the environment. Depending of the dose of doxorubicin, it is possible to obtain a model of heart dilatation and ventricular hypokinesia with or without clinical symptoms of HF, with a different mortality.
Tessier
Dominique
D
Cardiology Unit, National Veterinary School of Alfort, France.
Lajos
Paul
P
Braunberger
Eric
E
Pouchelon
Jean-Louis
JL
Carpentier
Alain
A
Chachques
Juan Carlos
JC
Chetboul
Valerie
V
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D001166:Arteriovenous Shunt, Surgical; D002339:Carotid Arteries / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D006041:Goats; D006333:Heart Failure / Q000139:chemically induced* / Q000175:diagnosis / Q000209:etiology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007601:Jugular Veins / Q000601:surgery; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin