Congestive heart failure: experimental model

Introduction: Surgically induced, combined volume and pressure overload has been used in rabbits to create a simplified and reproducible model of acute left ventricular (LV) failure. Materials and Methods: New Zealand white male rabbits (n=24, mean weight 3.1 +/- 0.2 kg) were randomly assigned to either the Control group (n=10) or to the Heart Failure group (HF, n=14). Animals in the Control group underwent "sham" procedures. Animals in the HF group underwent procedures to induce LV volume overload by inducing severe aortic valve regurgitation with aortic cusp disruption and pressure overload using an occlusive silver clip positioned around the pre-renal abdominal aorta. Results: Following Procedure-1 (volume overload) echocardiography confirmed severe aortic regurgitation in all animals in the HF group, with increased mean pulse pressure difference from 18 +/- 3 to 38 +/- 3 mmHg (P < 0.0001). After Procedure-2 (pressure overload) all animals in the HF group showed clinical and echocardiographic signs of constriction of the abdominal aorta and echocardiography confirmed progressively declining LV function. At the end of the protocol there was a significant increase of the heart/body weight ratio in the HF group vs. Control group (4.6 +/- 0.2 vs. 2.9 +/- 0.1 g/kg, P <0.05), and echocardiography showed in HF group significant increase of the LV end-diastolic diameter (2.15 +/- 0.09 vs. 1.49 +/- 0.03 cm, P <0.001) and reduction of the LV shortening fraction (26.3 +/- 3.8 vs. 41.3 +/- 1.6%, P<0.001). Conclusion: This experimental model: (a) consistently produces LV hypertrophy/dilatation and subsequent congestive heart failure, (b) provides new data on the time course of LV dilatation, hypertrophy and failure, (c) allows study of the progress and evolution of LV systolic and diastolic dysfunction in the presence of induced LV failure, (d) is suitable to study intervention or pharmacological administration to reduce the negative effects of acute LV failure.