Chronic heart failure induced by multiple sequential coronary microembolization in sheep

Objective: Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We aimed to establish a stable and reproducible animal model of chronic heart failure in sheep. Methods: Sheep (n=8, 77 +/- 4 kg) were anesthesized and a 5F sheath was implanted into the left carotid artery. The left main coronary artery was catheterized under flouroscopic guidance and bolus injection of polysterol microspheres (90 mu m, n=25.000) was performed. Microembolization (ME) was repeated up to three times in two to three week intervals until animals started to develop stable clinical signs of heart failure. Clinical and echocardiographic data were analyzed at baseline (base) and at three months (3 mo) after first ME. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. Another four healthy sheep (79 +/- 6 kg) served as control animals. Results: All animals developed clinical signs of heart failure as indicated by increased heart rate at rest (68 +/- 4 bpm (base) to 93 +/- 5 bpm (3 mo) (p<0.05)), increased respiratory rate at rest (28 +/- 5 (base) to 38 +/- 7 (3 mo) (p<0.05)) and increased body weight 77 +/- 2 kg to 81 +/- 2 kg (p<0.05) due to pleural effusion, peripheral edema and ascites. Echocardiographic evaluation revealed significantly an increase of left ventricular enddiastolic diameter from 46 +/- 3 mm (base) to 61 +/- 4 mm (3 mo) (p<0.05). Clinically and echocardiographically no significant changes were revealed in healthy control animals. Conclusions: We conclude that multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and echocardiographical signs of chronic ischemic cardiomyopathy. The present model may be suitable in experimental work on heart failure and left ventricular assist devices, e. g. for studying the impact of mechanical unloading, mechanisms of recovery and reverse remodeling.