Dapagliflozin improves left ventricular remodeling and aorta sympathetic tone in a pig model of heart failure with preserved ejection fraction. 2022-08-02
Heart failure with preserved ejection fraction (HFpEF) is a difficult disease with high morbidity and mortality rates and lacks an effective treatment. Here, we report the therapeutic effect of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), on hypertension + hyperlipidemia-induced HFpEF in a pig model. HFpEF pigs were established by infusing a combination of deoxycorticosterone acetate (DOCA) and angiotensin II (Ang II), and Western diet (WD) feeding for 18 weeks. In the 9th week, half of the HFpEF pigs were randomly assigned to receive additional dapagliflozin treatment (10 mg/day) by oral gavage daily for the next 9 weeks. Blood pressure, lipid levels, echocardiography and cardiac hemodynamics for cardiac structural and functional changes, as well as epinephrine and norepinephrine concentrations in the plasma and tissues were measured. After sacrifice, cardiac fibrosis, the distribution of tyrosine hydroxylase (TH), inflammatory factors (IL-6 and TNF-α) and NO-cG
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