Entresto therapy effectively protects heart and lung against transverse aortic constriction induced cardiopulmonary syndrome injury in rat

This study tested the hypothesis that entresto therapy effectively protected heart and lung against cardio- pulmonary syndrome (CPS) caused by transverse aortic constriction (TAC) in rat. Adult-Male SD rats (n = 36) were equally categorized into group 1 [sham-operated control (SC)], group 2 [SC + enalapril (7 mg/kg/day) since day-28 after TAC induction], group 3 [SC + entresto (30 mg/kg/day) since day-14 after TAC induction], group 4 (TAC only), group 5 (TAC + enalapril) and group 6 (TAC + entresto) and euthanized at day 60 after TAC induction. By day 60, the left-ventricular (LV) ejection fraction was significantly lower in group 4 than in other groups and significantly lower in groups 5 and 6 than in groups 1 to 3, whereas the ratios of heart and lung weights to tibial-length as well as the right-ventricular-systolic blood pressure exhibited an opposite pattern among the groups (all P<0.001). The sarco- mere-length (SL), LV fibrotic area, cardiomyocyte size, and lung injury score were highest in group 4, lowest in groups 1 to 3 and significantly lower in group 6 than in group 5 (all P<0.0001). The protein expressions of fibrotic (Smad3/ TGF-β), apoptotic (mitochondrial-Bax/cleaved-caspase3/PARP) and DNA-damaged (γ-H2AX) markers in lung and LV myocardium as well as oxidative (NOX-1/NOX2/oxidized protein) in LV myocardium exhibited an identical pattern of SL (all P<0.0001). The protein expressions of pressure/volume overload (BNP/MHC-β) mitochondrial-damaged (cytosolic cytochrome-C) of LV myocardium exhibited an identical pattern of SL (all P<0.001). In conclusion, Entresto is non-inferior to enalapril for protecting the heart-lung against CPS.