Early changes in contractility indices and fibrosis in two minimally invasive congestive heart failure models

Heart failure is a common and often fatal disease. Numerous animal models are used to study its aetiology, progression and treatment. This article aims to demonstrate two minimally invasive models of congestive heart failure in a rabbit model and a precise method to assess cardiac performance.

Fifty New Zealand White rabbits underwent cervicotomy incision and were then divided into three groups. Aortic regurgitation (AR group) was induced in 17 animals by catheter lesion through the right carotid artery, proximal aortic constriction (AC group) was created in 17 animals by metallic clip placement in the ascending aorta through a neck incision, while 16 animals served as controls (CO group). Eight weeks later, myocardial function and contractility indices were assessed by sonomicrometry crystals. Hearts were then collected for morphometric measurements and left ventricular tissues were subjected to immunohistochemical analysis of fibrosis, necrosis and apoptosis. Statistical analysis was by analysis of variance (ANOVA) with a Dunnett's post hoc test or by Kruskal-Wallis test with Dunn's post hoc test as appropriate, with significance at p< or =0.05.

The model of aortic regurgitation indicated early stages of heart failure by volume overload with increased end-diastolic and end-systolic volumes, stroke volume, cardiac output and pressure-volume loop areas. The elastance was higher in the control group compared with that in the AC and AR groups (131.00+/-51.27 vs 88.77+/-40.11 vs 75.29+/-50.70; p=0.01). The preload recruitable stroke work was higher in the control group compared with that in the AC and AR groups (47.70+/-14.19 vs 33.87+/-7.46 vs 38.58+/-9.45; p=0.01). Aortic constriction produced left ventricular concentric hypertrophy. Fibrosis appeared in both heart failure models and was elevated by aortic constriction when compared with that in controls. Necrosis and apoptosis indices were very low in all the groups. Clinical signs of congestive heart failure were not present.

The two heart failure models we describe were relatively simple to create and maintain, minimally invasive, accurate, inexpensive and, importantly, had a low mortality rate. These models rapidly induced deterioration of contractility indices and onset of fibrosis, the hallmarks of early myocardial dysfunction associated with heart failure. Sonomicrometry assessments were able to detect early contractility changes prior to clinical signs.