BALB/c mice uniformly developed congestive heart failure post-transverse aortic constriction, and enalapril effectively improved survival and reduced lung congestion in this model.
Does the BALB/c mouse strain provide a better model for TAC-induced progressive heart failure than C57BL/6J mice, and does enalapril improve outcomes in this model?
BALB/c mice are a more reliable model for studying progressive congestive heart failure and evaluating novel therapies post-transverse aortic constriction compared to the commonly used C57BL/6J strain.
INTRODUCTION: Murine transverse aortic constriction (TAC) is a frequently used model of pressure overload-induced left ventricular (LV) remodeling. However, there is considerable variability in disease progression to overt heart failure (HF) development in the most commonly used strain of mice (i.e., C57BL/6J). Studies have shown that C57BL/6J mice are more resistant than BALB/c mice to congestive HF development following myocardial infarction or angiotensin II-induced hypertension. Therefore, we tested the hypothesis that BALB/c mice may be a better research model to study TAC-induced progressive HF. METHODS: Following sham or TAC surgery in both C57BL/6J (n = 29) and BALB/c (n = 32) mice, we evaluated cardiac dimensions and function by echocardiography at 2, 4, 8, and 12 weeks and monitored survival throughout the study. In a separate cohort of BALB/c mice, we repeated the study in the presence of the angiotensin converting enzyme inhibitor enalapril or a vehicle initiated 2 weeks post-TAC and administered for 6 weeks. At the end of the studies, we assessed the heart weight, lung weight, and plasma brain natriuretic peptide (BNP) concentration. RESULTS: Following comparable TAC, both C57BL/6J and BALB/c mice showed significant LV remodeling compared with the sham control mice. BALB/c mice progressively developed systolic dysfunction, LV dilation, lung congestion, and significant mortality, whereas C57BL/6J mice did not. In the separate cohort of BALB/c TAC mice, enalapril significantly reduced the heart weight, lung weight, and plasma BNP concentration and improved survival compared with the vehicle control. DISCUSSION: BALB/c mice uniformly developed congestive HF post-TAC. Enalapril was effective in improving survival and reducing lung congestion in this model. The data suggest that BALB/c mice may be a better research tool than C57BL/6J mice to study TAC-induced disease progression to HF and to evaluate novel therapies for the treatment of chronic HF with reduced ejection fraction.
Tannu et al. (Tue,) conducted a other in Congestive heart failure (n=61). Transverse aortic constriction (TAC) and Enalapril vs. Sham surgery and Vehicle was evaluated on Cardiac dimensions, function, survival, heart weight, lung weight, and plasma BNP concentration. BALB/c mice uniformly developed congestive heart failure post-transverse aortic constriction, and enalapril effectively improved survival and reduced lung congestion in this model.