An Ovine Model of Chronic Heart Failure: Echocardiographic and Tissue Doppler Imaging Characterization

Abstract

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.

Animal Models of Heart Failure

“…Serial administration of intracoronary and intravenous doxorubicin induces toxic DCM in dogs, [131][132][133] sheep, 134,135 and, more recently, in cows. 136 As in rodents, doxorubicin cardiotoxicity is dose dependent and characterized by myocyte injury, myocyte and endothelial cell loss and apoptosis, microvascular insufficiency, and oxidative stress.…”

Bovine Model of Doxorubicin‐Induced Cardiomyopathy

“…The large number of mitochondria in the heart and the strong affinity of anthracyclines for the inner mitochondrial membrane phospholipid cardiolipin contribute to the mitochondrial accumulation of doxorubicin and predispose cardiac myocytes to doxorubicin toxicity [30]. As such, multiple investigators have used anthracyclines such as doxorubicin to induce cardiomyopathy and HF in a variety of large animal models that include dogs and sheep [10–17, 31]. Large animal studies that have used sequential weekly doxorubicin doses for a circumscribed period (as was done in our study) report a cardiomyopathy that is progressive over the long term without evidence of spontaneous improvement [10–13, 16].…”

“…As myocardial recovery most often has been reported in patients with idiopathic dilated cardiomyopathy [5], our objective in this study was to develop a nonischemic bovine model of cardiomyopathy to provide a substrate for studying device-based therapies for HF. For this purpose, we used doxorubicin, a broad-spectrum antineoplastic drug with dose-dependent cardiotoxicity that has been used to induce chronic HF in several animal species that include sheep [10, 11] and dogs [12–17]. …”

Atrial Remodeling in an Ovine Model of Anthracycline-Induced Nonischemic Cardiomyopathy: Remodeling of the Same Sort

“…To determine whether the changes observed in prior studies were specific to the model used or a result of HF, we undertook detailed evaluation of the atrial electrical, functional, and structural abnormalities that develop in a recently characterized ovine model of doxorubicin‐induced nonischemic cardiomyopathy 12,13 …”