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

• Grant number: 09/08730-2
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: July 01, 2009
• End date: August 31, 2010
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Orlando Petrucci Jr
• Grantee: Orlando Petrucci Jr
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Background: Heart failure is a common and often fatal disease. Numerous animal models are used to study its etiology, progression and treatment. The aim of this paper is to demonstrate two minimally invasive models of congestive heart failure in a rabbit model and a precise way to assess cardiac performance.Methods: Fifty New Zealand White rabbits underwent cervicotomy incision and were then divided into 3 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, and 16 animals served as controls (CO group). Eight weeks later myocardial function and contractility indexes were assessed by sonomicrometry crystals. Hearts were then collected for morphometric measurements and left ventricular tissues underwent immunohistochemical analysis of fibrosis, necrosis, and apoptosis. Statistical analysis was by ANOVA with a Dunnet post hoc test or by Kruskal-Wallis test with Dunns post hoc test as appropriate with significance at pd0.05.Results: 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 to 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 to 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 to controls. Necrosis and apoptosis indexes were very low in all groups. Clinical signs of congestive heart failure were not present. Conclusions: 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 indexes 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. (AU)