Possible mechanism of effect of the empagliflozin on cardiovascular mortality
| Autor: | A. V. Karpushev, M. V. Krasnova, D. Yu. Ivkin, V. B. Mikhailova, E. S. Klimenko, S. V. Okovityi, A. N. Kulikov |
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| Jazyk: | ruština |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Разработка и регистрация лекарственных средств, Vol 0, Iss 0 (2023) |
| Druh dokumentu: | article |
| ISSN: | 2305-2066 2658-5049 |
| DOI: | 10.33380/2305-2066-2024-13-4-1868 |
| Popis: | Introduction. The development of heart failure is closely associated with the appearance of life threatening arrhythmias, which are often a terminal event for these patients. An analysis of randomized clinical trials of inhibitors of sodium-glucose cotransporter type 2 indicates the clinically significant potential of these drugs as agents with antiarrhythmic properties. However, at the moment the full mechanism by which this effect can be realized is still not fully understood.Aim. To evaluate the effect of empagliflozin on the transmembrane calcium currents and the intracellular calcium transients on isolated ventricular cardiomyocytes of mice under conditions of normoglycemia.Materials and methods. In the experiment, ventricular cardiomyocytes were isolated from 12 outbred male mice. 2 groups were formed: group № 1 – control ventricular cardiomyocytes; group № 2 – ventricular cardiomyocytes after two hours incubation with 5 µmol/L empagliflozin solution. Transmembrane calcium currents were recorded and intracellular calcium transients were assessed.Results and discussion. Incubation of ventricular cardiomyocytes with empagliflozin significantly increased ICa current density and accelerated Ca2+ temporal dynamics. The amplitude of the Ca2+ wave and the rate of rise and decay were increased and the duration of the Ca2+ wave was shortened.Conclusion. The result of the experiment indicates that empagliflozin is able to modulate Ca2+-dependent mechanism of the excitation-contraction-coupling, enhancing and accelerating Ca2+ release into cytoplasm and reuptake. This presumably can optimize, namely reduce the time of systole and enhance it, which may be one of the important elements in the manifestation of empagliflozin antiarrhythmic properties. |
| Databáze: | Directory of Open Access Journals |
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