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 established a stable and reproducible animal model of chronic
heart failure in sheep and aimed to investigate the hemodynamic changes of this animal model of chronic
heart failure in sheep. In five sheep (n = 5, 77 +/- 2 kg), chronic
heart failure was induced under fluoroscopic guidance by multiple sequential microembolization through bolus injection of polysterol
microspheres (90 microm, n = 25.000) into the left main coronary artery. Coronary microembolization (CME) was repeated up to three times in 2 to 3-week intervals until animals started to develop stable signs of
heart failure. During each operation, hemodynamic monitoring was performed through implantation of
central venous catheter (central venous pressure [CVP]), arterial pressure line (mean arterial pressure [MAP]), implantation of a right
heart catheter {Swan-Ganz
catheter (mean pulmonary arterial pressure [PAP mean])}, pulmonary capillary wedge pressure (PCWP), and cardiac output [CO]) as well as pre- and postoperative clinical investigations. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. All animals developed clinical signs of
heart failure as indicated by increased heart rate (HR) at rest (68 +/- 4 bpm [base] to 93 +/- 5 bpm [3 mo][P < 0.05]), increased respiratory rate (RR) 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. Hemodynamic signs of
heart failure were revealed as indicated by increase of HR, RR, CVP, PAP, and PCWP as well as a decrease of CO, stroke volume, and MAP 3 months after the first CME. Multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and hemodynamic signs of chronic ischemic
cardiomyopathy. The present model may be suitable in experimental work on
heart failure and left
ventricular assist devices, for example, for studying the impact of mechanical unloading, mechanisms of recovery, and reverse remodeling.