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Effects of empagliflozin in an experimental model of chronic heart failure in normoglycemic rats

Kulikov A.N.1, Okovityj S.V.2, Ivkin D.Yu.2, Karpov A.A.3, Lisitsky D.S.2, Lyubishin M.M.2, Alekseeva P.A.2, Pitukhina N.N.2, Smirnov A.V.1, Kayukov I.G.1, Beresneva O.N.1, Parusova E.V.1
1 – State Budgetary Educational Institution of Higher Professional Education, "I.P. Pavlov First St.-Petersburg State Medical University " of the RF Ministry of Health Care, L. Tolstogo 6/8, St.-Petersburg 197022
2 – Federal State Budgetary Institution of Higher Education, "St. Petersburg State Chemistry and Pharmaceutics Academy ", Professora Popova 14A, St. Petersburg 1970376
3 – Federal State Budgetary Institution "Federal Almazov North-West Medical Research Center" of the Ministry of Health of the Russian Federation, Akkuratova 2, St. Petersburg 197341

Keywords: empagliflozin, CHF, experimental model

DOI: 10.18087/rhfj.2016.6.2289

Background. EMPA-REG OUTCOME trial results shows that an inhibitor of sodium glucose cotransporter 2 (of SGLT2) empagliflozin patients significantly decrease the heart failure hospitalization in patients with type 2 diabetes. Relative risk reduction of heart failure hospitalization (35%) was comparable with a degree of reduction of cardiovascular risk (38%). Aim. To evaluate in experimental setting the efficacy of a sodium-glucose transporter 2 (SGLT2), empagliflozin, for treatment of chronic heart failure in the absence of carbohydrate metabolic disorders. Materials and methods. CHF was modeled in rats by permanent ligation of the left coronary artery. Rats were divided into three groups: group 1, rats with CHF, which were treated with empagliflozin (1 mg/kg) for three months starting one month after the surgery; group 2, rats with CHF not treated with empagliflozin; and group 3, a control group consisting of sham-operated rats. Echocardiography was performed monthly for all rats with evaluation of left ventricular (LV) dimensions and volumes, LV contractility indexes (ejection fraction), and systemic hemodynamics (stroke volume and cardiac output). At the end of experiment, treadmill exercise tolerance of rats, heart mass and LV mass were evaluated. Results. Exercise tolerance was better in CHF rats treated with empagliflozin (treadmill exercise time, 900±110 s vs. 645±110 s, р=0.0004); they had higher cardiac output at rest (80±30.1 ml/min vs. 57±19.4 ml/min, p<0.025), greater end-diastolic volume (0.50±0.14 ml vs. 0.39±0.08, p=0.028), and greater LV mass (1.09±0.19 g vs. 0.69±0.10 g, p=0.012) than untreated rats. In rats of group 1, the LV stroke volume, end-diastolic volume, ejection fraction, and cardiac output were increasing over three months of the empagliflozin treatment. These changes were not observed in the reference group (group 2). Conclusion. The antidiabetic drug, empagliflozin, improved exercise tolerance and LV functional parameters in rats with CHF in the absence of carbohydrate metabolic disorders. The effect of empagliflozin on LV remodeling requires further study.
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Kulikov A.N., Okovityj S.V., Ivkin D.Yu., Karpov A.A., Lisitsky D.S., Lyubishin M.M. et al. Effects of empagliflozin in an experimental model of chronic heart failure in normoglycemic rats. Russian Heart Failure Journal. 2016;17 (6):454–460

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