Acute antiarrhythmic effects of SGLT2 inhibitors-dapagliflozin lowers the excitability of atrial cardiomyocytes
In recent years, SGLT2 inhibitors have become an integral part of heart failure therapy, and several mechanisms contributing to cardiorenal protection have been identified. In this study, we place special emphasis on the atria and investigate acute electrophysiological effects of dapagliflozin to as...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
03 January 2024
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| In: |
Basic research in cardiology
Year: 2024, Jahrgang: 119, Heft: 1, Pages: 93-112 |
| ISSN: | 1435-1803 |
| DOI: | 10.1007/s00395-023-01022-0 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s00395-023-01022-0 Verlag, kostenfrei, Volltext: https://link.springer.com/article/10.1007/s00395-023-01022-0 
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| Verfasserangaben: | Amelie Paasche, Felix Wiedmann, Manuel Kraft, Fitzwilliam Seibertz, Valerie Herlt, Pablo L. Blochberger, Natasa Jávorszky, Moritz Beck, Leo Weirauch, Timon Seeger, Antje Blank, Walter E. Haefeli, Rawa Arif, Anna L. Meyer, Gregor Warnecke, Matthias Karck, Niels Voigt, Norbert Frey, Constanze Schmidt |
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| 245 | 1 | 0 | |a Acute antiarrhythmic effects of SGLT2 inhibitors-dapagliflozin lowers the excitability of atrial cardiomyocytes |c Amelie Paasche, Felix Wiedmann, Manuel Kraft, Fitzwilliam Seibertz, Valerie Herlt, Pablo L. Blochberger, Natasa Jávorszky, Moritz Beck, Leo Weirauch, Timon Seeger, Antje Blank, Walter E. Haefeli, Rawa Arif, Anna L. Meyer, Gregor Warnecke, Matthias Karck, Niels Voigt, Norbert Frey, Constanze Schmidt |
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| 520 | |a In recent years, SGLT2 inhibitors have become an integral part of heart failure therapy, and several mechanisms contributing to cardiorenal protection have been identified. In this study, we place special emphasis on the atria and investigate acute electrophysiological effects of dapagliflozin to assess the antiarrhythmic potential of SGLT2 inhibitors. Direct electrophysiological effects of dapagliflozin were investigated in patch clamp experiments on isolated atrial cardiomyocytes. Acute treatment with elevated-dose dapagliflozin caused a significant reduction of the action potential inducibility, the amplitude and maximum upstroke velocity. The inhibitory effects were reproduced in human induced pluripotent stem cell-derived cardiomyocytes, and were more pronounced in atrial compared to ventricular cells. Hypothesizing that dapagliflozin directly affects the depolarization phase of atrial action potentials, we examined fast inward sodium currents in human atrial cardiomyocytes and found a significant decrease of peak sodium current densities by dapagliflozin, accompanied by a moderate inhibition of the transient outward potassium current. Translating these findings into a porcine large animal model, acute elevated-dose dapagliflozin treatment caused an atrial-dominant reduction of myocardial conduction velocity in vivo. This could be utilized for both, acute cardioversion of paroxysmal atrial fibrillation episodes and rhythm control of persistent atrial fibrillation. In this study, we show that dapagliflozin alters the excitability of atrial cardiomyocytes by direct inhibition of peak sodium currents. In vivo, dapagliflozin exerts antiarrhythmic effects, revealing a potential new additional role of SGLT2 inhibitors in the treatment of atrial arrhythmias. | ||
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| 650 | 4 | |a Atrial fibrillation | |
| 650 | 4 | |a Dapagliflozin | |
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| 650 | 4 | |a SGLT2 inhibitors | |
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