Heart failure is one of the fastest-growing epidemics worldwide in health care today. Although a wide variety of animal models exist to create chronic
heart failure, there are few truly successful, reproducible models with ischemic dilation and
mitral regurgitation. Six healthy sheep (36 ± 5 kg) underwent multiple, strategic coronary artery
ligations on the left ventricle (LV). Six to eight
ligations were performed transmurally on three of four segments of the LV: anterior, lateral, and posterior. Side branches of the left anterior descending and circumflex arteries were ligated to create multiple, patchy areas of
myocardial infarction. Cardiac global and regional systolic function was assessed by echocardiography and cardiac magnetic resonance imaging (MRI). The extent, the characteristics, and the location of the
myocardial infarction were qualitatively and quantitatively assessed by late
gadolinium enhancement imaging. The overall mortality rate was 16.7% (1/6 animals). Animals who survived showed a significantly reduced ejection fraction (mean 60 ± 5% to 28 ± 7%; P < 0.05); additionally, two out of the remaining five (40%) animals developed mild to moderate
mitral regurgitation quantified by cardiac MRI. Furthermore, each animal developed clinical signs of
heart failure (
tachycardia,
dyspnea, and
tachypnea) consistent with global,
dilated cardiomyopathy noted on MRI. Creating and reproducing a model of global, ischemic
cardiomyopathy with functional
mitral regurgitation is an arduous task. We have developed a promising model of ischemic
heart failure using multiple
ligations, which mimics the sequelae of human
cardiomyopathy. Our proposed model is highly effective, reproducible, and may be used for experimental research on
heart failure (cardiac
assist devices, heart transplant, etc.).