Early intervention with sacubitril/valsartan attenuated pressure overload-induced ventricular fibrosis to 1.5-fold of sham levels, which was superior to the 2.0-fold increase seen with valsartan alone.
Does sacubitril/valsartan reduce ventricular fibrosis and mitochondrial dysfunction compared to valsartan alone in pressure overloaded rat hearts?
Sacubitril/valsartan provides superior cardioprotection over valsartan alone by reducing ventricular fibrosis and mitochondrial dysfunction in a rat model of pressure overload.
Absolute Event Rate: 1.5% vs 2.8%
p-value: p=<0.05
Left ventricular remodeling due to pressure overload is associated with poor prognosis. Sacubitril/valsartan is the first-in-class Angiotensin Receptor Neprilysin Inhibitor and has been demonstrated to have superior beneficial effects in the settings of heart failure. The aim of this study was to determine whether sacubitril/valsartan has cardioprotective effect in the early intervention of pressure overloaded hearts and whether it is superior to valsartan alone. We induced persistent left ventricular pressure overload in rats by ascending aortic constriction surgery and orally administrated sacubitril/valsartan, valsartan, or vehicle one week post operation for 10 weeks. We also determined the effects of sacubitril/valsartan over valsartan on adult ventricular myocytes and fibroblasts that were isolated from healthy rats and treated in culture. We found that early intervention with sacubitril/valsartan is superior to valsartan in reducing pressure overload-induced ventricular fibrosis and in reducing angiotensin II-induced adult ventricular fibroblast activation. While neither sacubitril/valsartan nor valsartan changes cardiac hypertrophy development, early intervention with sacubitril/valsartan protects ventricular myocytes from mitochondrial dysfunction and is superior to valsartan in reducing mitochondrial oxidative stress in response to persistent left ventricular pressure overload. In conclusion, our findings demonstrate that sacubitril/valsartan has a superior cardioprotective effect over valsartan in the early intervention of pressure overloaded hearts, which is independent of the reduction of left ventricular afterload. Our study provides evidence in support of potential benefits of the use of sacubitril/valsartan in patients with resistant hypertension or in patients with severe aortic stenosis.
Li et al. (Mon,) conducted a other in Left ventricular pressure overload (n=40). Sacubitril/valsartan vs. Valsartan (31 mg/kg/day) or Vehicle was evaluated on Ventricular fibrosis (fold increase in collagen deposition compared to sham) (p=<0.05). Early intervention with sacubitril/valsartan attenuated pressure overload-induced ventricular fibrosis to 1.5-fold of sham levels, which was superior to the 2.0-fold increase seen with valsartan alone.