Influence of Enalapril Therapy Schedule on the Progression of the Disease in Dilated Cardiomyopathic Syrian Hamsters (Bio TO-2 strain)
The influence of enalapril therapy schedule on the progression of the disease in terms of hemodynamic, cardiac remodelling and survival was assessed in cardiomyopathy 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. 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. None of the available models reproduce completely the progression of the natural disease observed in human because each model has its own limitations and interest. Among them, the model of cardiomyopathic Syrian hamsters has been used for many years as an animal model of CHF.
Two groups of strains were successively derived from the initial polymyopathic line Bio 1.50. The first group (e.g. Bio 14.6, UM-X7.1, CHF 146 and CHF 147 strain) is mainly characterized by a significant hypertrophy of the cardiac muscle whereas the second group (e.g. Bio 53.58 and Bio TO-2 strain) shows a wide dilation of ventricles without wall hypertrophy. The cardiomyopathic hamsters do not show any clinical or histological signs of the disease before 30 days of age. Three successive phases are then 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.
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