The Combined Empagliflozin and Sacubitril/Valsartan Therapy Attenuates Isoproterenol-Induced Heart Failure in Rats: Functional, Molecular, and Structural Insights.

Abstract

PURPOSE: The idea behind this study was to assess the effects of empagliflozin and sacubitril/valsartan and their combination on isoproterenol-induced heart failure (HF) and underlying molecular mechanisms. METHODS: HF was induced with 7-day isoproterenol (5 mg/kg daily), confirmed by ejection fraction below 55% after 4 weeks. HF rats received empagliflozin, sacubitril/valsartan, or both for 4 weeks. Parameters measured included hemodynamics, cardiac function, redox status, and histomorphology. RESULTS: Isoproterenol impaired hemodynamics and cardiac function, increased oxidative damage, and altered cardiac structure. All treatments were cardioprotective; however, combined empagliflozin and sacubitril/valsartan therapy had the most pronounced effect. CONCLUSION: Combined empagliflozin and sacubitril/valsartan showed superior cardioprotection in HF, primarily by enhancing antioxidative effects. These findings support early use of both drugs in HF treatment.