An ovine model of chronic heart failure: echocardiographic and tissue Doppler imaging characterization.
OBJECTIVE
Heart failure in the western world is a major health-care issue. In order to validate novel surgical or pharmacological treatments, reproducible animal models of left ventricular dysfunction are necessary. In the current study, we report our data and experience with a model of toxin-induced heart failure in the sheep.


METHODS
Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until standard echocardiographic and tissue Doppler imaging detection of myocardial systolic dysfunction. The animals were assessed 1 month later and harvested. Indices of cardiac function from baseline to last day of protocol were recorded and their differences were evaluated by a Wilcoxon rank test for paired data.


RESULTS
Ten sheep received 2.5 +/- 0.7 intracoronary injections of a cumulative dose of 88.8 +/- 25 mg/m2 doxorubicin. All available parameters demonstrated signs of severe cardiac dysfunction with statistical significance. All hearts demonstrated severe histological lesions, some of which were consistent with doxorubicin-induced toxicity.


CONCLUSIONS
The present study shows that this ovine model is reproducible and stable. It can therefore be relevant to the study of chronic heart failure. It will be incorporated in our future studies concerning novel treatments (such as cell therapy) of nonischemic dilated cardiomyopathy.
Borenstein
Nicolas
N
IMM Recherche (Centre d'Expérimentation et de Recherche Appliquée) Paris, France. nicolas.borenstein@imm.fr
Bruneval
Patrick
P
Behr
Luc
L
Laborde
François
F
Montarras
Didier
D
Daurès
Jean Pierre
JP
Derumeaux
Geneviève
G
Pouchelon
Jean-Louis
JL
Chetboul
Valérie
V
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler / Q000379:methods*; D006333:Heart Failure / Q000097:blood / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D012756:Sheep; D013318:Stroke Volume / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology*
D009320:Atrial Natriuretic Factor