Abstract 12147: Bisoprolol Improves Rv Function and Hypertrophy via Anti-fibrotic and Anti-hypertrophic Effects in PA Banded Rat
Introduction: Right ventricle (RV) failure is one of the significant complications in patients with congenital heart disease involving right-sided obstructive lesions (e.g., tetralogy of Fallot), pulmonary hypertension. Effective medical treatment for decompensated RV remains to be elucidated. While beta blockers are known to reduce mortality in patients with left side heart failure by inhibiting cardiac remodeling, however their effects for RV failure are unknown. Objective:To investigate the effects of β1 selective blocker, bisoprolol on RV function using a RV failure rat model.
Method: RV failure model rats were surgically generated by pulmonary artery banding (PAB) using SD rats. Those rats were treated with oral bisoprolol (low dose (LB) group; 0.1mg/kg n=12, high dose (HB) group 1mg/kg/day n=16) or water as control (n=12) for 4 weeks. RV PV loops were examined using micro catheter. For histological analysis of cardiac muscles remodeling, Masson's trichrome staining was performed. mRNA expression was quantified using real-time PCR.
Results: Median survival time for bisoprolol-treated rats was significantly longer compared to the control rats, while no significant difference noted between the LB and HB groups (LB : 28.8, HB: 29.7 vs Control: 20.5 days; p < 0.01). No significant difference was observed in HR, SBP, RVP, however, there was a significant increase in RV cardiac output (P < 0.05), RV EDP, end-systolic elastance, and end-diastolic elastance (p < 0.01) derived from RV PV loop in the LB and HB groups. The rate of fibrosis in RV was significantly lower in the LB and HB groups (p < 0.01) as well as mRNA expression of Pro-collagen 3, CTGF, and periostin in the right ventricles (p < 0.05). RV/LV+S was also deareased signifacantly in the HB group (P < 0.01).
Conclusions: In PAB rats, both low dose and high dose bisoprolol were effective for RV failure and reduced mortality without RV pressure reduction. Of importance, the effect directly attributed to maintenance of RV myocardial compliance by dose-dependent inhibit cardiac fibrotic change and RV hypertrophy. These results suggest that bisoprolol may be a treatment option for RV failure.
- © 2012 by American Heart Association, Inc.