Abstract
The influence of enalapril therapy schedule on the progression of the disease in terms of hemodynamics, cardiac remodeling and survival was assessed in cardiomyopathic Syrian hamsters (CMHs). CMHs (Bio TO-2 dilated strain) were treated orally with enalapril at 20 mg/kg/day from 60 to 200 (early treatment), from 120 to 200 (late treatment) or 120 to 250 (prolonged treatment) days of age. In survival studies, CMHs were treated until 90% of controls are death. Early, late and prolonged treatments significantly decreased mean arterial blood pressure (-23%, -27% and -22%, respectively), but had no effects on cardiac output and stroke volume. Late and prolonged treatments significantly decreased total peripheral resistance (-38% and -24%, respectively), but not early treatment. Only, prolonged treatment significantly decreased left ventricle (LV) end diastolic blood pressure (-60%). Early, late and prolonged treatments significantly decreased LV collagen density (-44%, -31% and -54%, respectively) and LV cavity area (-26%, -21% and -29%, respectively). Survival was significantly improved when enalapril was administered from 120 days of age, but not significantly when administered earlier. In conclusion, enalapril exerted beneficial effects (improvement of cardiac function and prolonged survival) more marked when the treatment was begun late in the evolution of congestive heart failure.
Highlights
Animal models remain widely used to improve the understanding of the pathophysiology of congestive heart failure (CHF) and to evaluate new drugs or new therapeutic strategies in this area
Because the dilated strain of Syrian cardiomyopathic hamsters mimics many clinical features of dilated cardiomyopathy in humans, typically exhibiting alteration of the cardiac function associated with a complex process of cardiac remodeling [4], this model is widely used for pharmacological studies [5,6,7]
During the hemodynamic and histomorphometry study, one enalapril-treated hamster spontaneously died before the end of the treatment period
Summary
Animal models remain widely used to improve the understanding of the pathophysiology of congestive heart failure (CHF) and to evaluate new drugs or new therapeutic strategies in this area. The model of cardiomyopathic Syrian hamsters has been used for many years as an animal model of CHF [1,2]. Three successive phases are generally observed during the disease: 1) a phase of necrosis which extends usually from 30 to 120 days of age, followed by 2) a phase of healing with fibrosis, moderate cardiac hypertrophy and/or dilation between 120 and 250 days of age and, 3) a terminal phase of heart failure [1]. Because the dilated strain of Syrian cardiomyopathic hamsters mimics many clinical features of dilated cardiomyopathy in humans, typically exhibiting alteration of the cardiac function associated with a complex process of cardiac remodeling [4], this model is widely used for pharmacological studies [5,6,7]
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