Sheep model of chronic heart failure induced by multiple sequential coronary microembolizations

Objectives: Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models of chronic heart failure are scarce. We tested wether ischemic cardiomyopathy and systolic heart failure can be reproduced experimentally by coronary microembolization (ME) in sheep.

Methods: Sheep (n=6.85±6kg) were anaesthetized, and a 5F sheath was implanted into the left carotid artery. The left main coronary artery was catheterized under flouroscopic guidance, and a bolus injection of polysterol microspheres (90µm, n= 12.500) was performed. ME was repeated up to three times in two week intervals until the animals started to develop stable clinical signs of heart failure.

Results: Clinical and echocardiographic data were analyzed at baseline (base) and at 3 months (3 mo) after the first ME. All animals developed heart failure, as indicated by increased heart rate (HR) and respiratory rate (RR) at rest and pronounced ascites. LV-end-diastolic-diameter (LVedD) increased significantly, while EF did not change. Histologic analysis demonstrated patchy fibrosis throughout the left ventricle 21.23% (±1.87) compared to 13.69% (±0.9) in the control group.

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Conclusion: We conclude that loss of contractile myocardium after coronary ME can induce LV dilatation and neurohumeral activation without a change in LV EF. EF is an insensitive parameter of this special phenotype of LV damage and dysfunction. The present model may prove suitable in experimental work on heart failure and left ventricular assist devices.