Ovine models for chronic heart failure.

PURPOSE: Testing and optimizing of surgical therapies for chronic heart failure (CHF) requires large animal models. CHF has been induced in several large animal species. Sheep have modest body mass increase and demonstrate docile behavior and are therefore a preferred species in research on surgical therapies for CHF METHODS: A literature search for existing ovine CHF models was performed, using search terms "sheep" and "heart failure". Relevant secondary references were traced. RESULTS: Rapid ventricular pacing produces rapid-onset CHFE Its severity ranges from moderate left ventricular failure to severe biventricular failure, depending on length and frequency of pacing. Its counterpart in human CHF is tachycardia-induced HF since it is reversible upon cessation of pacing. Myocardial damage models include CHF induced by cardiototoxic drugs and ischemia. Ischemia-based models include coronary microembolization, occlusion and ischemia/reperfusion models. The microembolization model is relevant to diabetic cardiomyopathy. Coronary occlusion models exhibit variable functional impairment, some with aneurysm formation, and some with mitral valve regurgitation, depending on occlusion localization. They are relevant to CHF following non-reperfused myocardial infarction. Coronary occlusion/reperfusion models are relevant to the occurrence of human ãã despite coronary artery recanalization. Pressure overload of left and right ventricle is induced by aortic and pulmonary artery banding, respectively. Hypertrophy precedes CHF as in patients with valve stenosis and hypertension. Volume overload is induced by valve damage or shunt creation. Atrioventricular valve regurgitation is the most important clinical counterpart. CONCLUSION: Several ovine CHF models exist. Since they exhibit important cardiac pathology differences, the choice of model should be based on the specific experimental question.

Partial mechanical circulatory support in an ovine model of post-infarction remodeling.

BACKGROUND: Full unloading of the left ventricle (LV) in chronic heart failure (CHF) induces reversal of LV dilation and geometric distortion. In this study we describe the partial unloading effects in ischemic CHF. METHODS: Six weeks after myocardial infarction, sheep were randomized to partial support ("pump," n = 5), as provided by the CircuLite Synergy micro-pump, or to no therapy ("sham," n = 6) for an additional 6 weeks. At baseline, and at 6 and 12 weeks after infarction, pressure-volume (PV) recordings were made. Systolic and diastolic functions were characterized by the end-systolic volume (ESV) where LV end-systolic pressure reached 90 mm Hg (V90), and the end-diastolic volume (EDV) where LV end-diastolic pressure reached 15 mm Hg (V15), respectively. Magnetic resonance imaging (MRI) was performed 6 and 12 weeks after infarction. During autopsy at 12 weeks, isolated LVs were weighed. Histologically, the degree of fibrosis in the non-infarcted area was assessed using systematic randomized sampling, and myocyte hypertrophy was measured by the mean linear intercept method. RESULTS: At 6 weeks, PV measurements showed a V90 and V15 increase (p = NS between groups). Six weeks later, V90 and V15 increased in the sham group. In the pump group, V90 decreased but V15 did not change significantly. At 6 weeks, MRI indicated no significant difference between groups. Six weeks later, in the sham group, EDV and ESV increased significantly. In the pump group, EDV decreased significantly and ESV trended to decrease. Sphericity index increased in the sham group and decreased in the pump group, although not significantly. Explanted LV masses were significantly higher in the sham group than in the pump group. The pump group had a decrease in fibrosis and less myocyte hypertrophy. CONCLUSION: Partial support 6 weeks after major myocardial infarction halts and reverses ventricular dilation and hypertrophy.