Dual Empagliflozin and Sacubitril/Valsartan Therapy Improves Ex Vivo Cardiac Function in a Rat Model of Heart Failure
Abstract
Background/Objectives: This study aimed to clarify the cardioprotective effects of combined empagliflozin and sacubitril/valsartan therapy in an experimental rat model of heart failure (HF). The main research question was whether dual treatment provides greater functional and molecular benefit than either monotherapy, with particular emphasis on oxidative stress, inflammation, apoptosis, and JAK2/STAT3 signaling. Methods: HF was induced in rats by 7-day isoproterenol administration and confirmed four weeks later by echocardiographic evidence of reduced ejection fraction (<55%). The animals were then assigned to healthy control, untreated HF, empagliflozin, sacubitril/valsartan, and combined empagliflozin/sacubitril/valsartan groups. Following four weeks of treatment, ex vivo cardiac function was evaluated using the Langendorff technique. Serum cardiospecific markers and natriuretic peptides were measured by ELISA. Oxidative stress parameters were determined in coronary venous effluent, while myocardial gene expression of selected (anti)oxidative, (anti)inflammatory, (anti)apoptotic, and signaling markers was assessed by RT-PCR. Myocardial collagen content was evaluated using Picrosirius red staining. Results: HF rats exhibited impaired ex vivo myocardial function, elevated cardiac injury markers, increased oxidative stress, upregulation of pro-inflammatory and pro-apoptotic genes, activation of JAK2/STAT3 signaling, and increased myocardial collagen content. Both…
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