Comparative efficacy of empagliflozin and drugs of baseline therapy in post-infarct heart failure in normoglycemic rats


The study aimed to investigate the effects of the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin on chronic heart failure (HF) in normoglycemic rats. The effects of empagliflozin were compared with the standard medications for HF, e.g., angiotensin-converting enzyme (ACE) inhibitor fosinopril, beta-blocker bisoprolol, and aldosterone antagonist spironolactone. Myocardial infarction (MI) was induced in male Wistar rats via permanent ligation of the left descending coronary artery. One-month post MI, 50 animals were randomized into 5 groups (n = 10): vehicle-treated, empagliflozin (1.0 mg/kg), fosinopril (10 mg/kg), bisoprolol (10 mg/kg), and spironolactone (20 mg/kg). All medications except empagliflozin were titrated within a month and administered per os daily for 3 months. Echocardiography, 24-hour urine volume test, and treadmill exercise tests were performed at the beginning and at the end of the study. Treatment with empagliflozin slowed the progression of left ventricular dysfunction: LV sizes and ejection fraction were not changed and the minute volume was significantly increased (from 52.0 ± 15.5 to 61.2 ± 21.2 ml/min) as compared with baseline. No deaths occurred in empagliflozin group. The 24-hour urine volume tends to be higher in empagliflozin and spironolactone groups than in vehicle and fosinopril group. Moreover, empagliflozin exhibited maximal physical exercise tolerance in comparison with all investigated groups (289 ± 27 s versus 183 ± 61 s in fosinopril group, 197 ± 95 s in bisoprolol group, and 47 ± 46 s in spironolactone group, p = 0.0035 for multiple comparisons). Sodium-glucose co-transporter 2 inhibitor empagliflozin reduced progression of left ventricular dysfunction and improved tolerance of physical exercise in normoglycemic rats with HF. Empagliflozin treatment was superior with respect to physical tolerance compared with fosinopril, bisoprolol, and spironolactone.

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Angiotensin-converting enzyme




Ejection fraction


Left ventricular fraction shortening


Heart failure


Heart rate


Interventricular septum thickness


Left atrial antero-posterior dimension


Left atrial long axis dimension


Left atrial short axis dimension


Left ventricular


Left ventricular end-diastolic


Left ventricle end-diastolic diameter


Left ventricle end-systolic diameters


Left ventricular end-systolic volumes


Left ventricular myocardium mass


Mitral annular plane systolic excursion


Myocardial infarction


Left ventricular minute volume


Left ventricular posterior wall thickness in diastole


Long axis dimensions


Right atrium short axis


Angiotensin aldosterone system


Right ventricle antero-posterior dimension


Left ventricular relative wall thickness


Sodium-glucose co-transporter 2


Stroke volume


Type 2 diabetes


Tricuspid annular plane systolic excursion


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We thank Kaiukov I.G., Beresneva O.N., and Galkina O.V. for their excellent technical assistance.


This work was supported by the St. Petersburg Chemical and Pharmaceutical University, Saint Petersburg, Russia.

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M. Krasnova: provision of study material, collection and assembly of data, data analysis and interpretation, and manuscript writing; A. Kulikov: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; S. Okovityi: conception and design, administrative support, data analysis, and interpretation; D. Ivkin: collection and assembly of data and data analysis; A. Smirnov: collection and assembly of data; A. Karpov: statistical data analysis and interpretation; E. Kaschina: data analysis and interpretation, manuscript writing advising, and final approval of manuscript. All authors read and approved the manuscript.

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Correspondence to Marina Krasnova.

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Krasnova, M., Kulikov, A., Okovityi, S. et al. Comparative efficacy of empagliflozin and drugs of baseline therapy in post-infarct heart failure in normoglycemic rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1649–1658 (2020).

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  • Chronic heart failure
  • Left ventricular dysfunction
  • Empagliflozin
  • Physical exercise
  • Normoglycemic rats