Arrhythmogenic Potential of Aminophylline and Its Modulation by
Salbutamol: Insights from Human Pluripotent Stem Cell-Derived
Cardiomyocytes

a 2025

Arrhythmogenic Potential of Aminophylline and Its Modulation by Salbutamol: Insights from Human Pluripotent Stem Cell-Derived Cardiomyocytes

PEŠL, Martin; Vrana KLIMOVIC; Deborah BECKEROVÁ; Daniil KABANOV; Martin SCUREK et al.

Základní údaje

Originální název

Arrhythmogenic Potential of Aminophylline and Its Modulation by Salbutamol: Insights from Human Pluripotent Stem Cell-Derived Cardiomyocytes

Autoři

PEŠL, Martin; Vrana KLIMOVIC; Deborah BECKEROVÁ; Daniil KABANOV; Martin SCUREK; Markéta BÉBAROVÁ ; Kristián BRAT; Jan PŘIBYL ; Zdeněk STÁREK a Vladimír ROTREKL

Vydání

The 49th Annual Meeting of the ESC Working Group on Cardiac Cellular Electrophysiology (EWGCCE), 2025

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30210 Clinical neurology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Označené pro přenos do RIV

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Aminophylline;Salbutamol;Cardiac electrophysiology;Arrhythmia;hPSC-derived cardiomyocytes;Atomic force microscopy;Multielectrode array

Změněno: 15. 7. 2025 13:35, MUDr. Martin Pešl, Ph.D.

Anotace

V originále

Cardiac side effects of pulmonary drugs are well-documented in clinical practice, with aminophylline, a methylxanthine bronchodilator, and salbutamol, a beta-2 adrenergic receptor agonist, both being associated with proarrhythmic effects. However, data on their direct impact on cardiac electrophysiology and contractility, particularly in combination, remain limited. Purpose: This study aimed to investigate the effects of aminophylline and salbutamol, both individually and in combination, on cardiac function using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and HL-1 cardiomyocytes. Methods: Beat rate (BR) and contraction force (CF) were assessed in hPSC-CMs using atomic force microscopy (AFM), while multielectrode array (MEA) recordings and calcium imaging were used to evaluate electrophysiological changes in HL-1 cardiomyocytes. Results: Aminophylline significantly increased BR, CF, and the frequency of rhythm irregularities in both hPSCCMs and HL-1 cardiomyocytes. Notably, calcium sparks were significantly elevated in HL-1 cardiomyocytes at 512 µM aminophylline, supporting its arrhythmogenic potential. In contrast, the combination of aminophylline and salbutamol exhibited a synergistic chronotropic and inotropic effect, while salbutamol mitigated aminophylline-induced arrhythmias. This protective effect is likely mediated via endothelial nitric oxide synthase activation through beta-2 adrenergic receptors. Conclusion: While aminophylline alone poses a significant risk of arrhythmias, its co-administration with salbutamol may enhance cardiovascular safety by reducing its proarrhythmic effects. These findings provide new insights into the cardiac safety of bronchodilator therapy and highlight the potential of hPSC-CM-based AFM platforms for evaluating direct drug effects on cardiac function

Citovat

PEŠL, Martin; Vrana KLIMOVIC; Deborah BECKEROVÁ; Daniil KABANOV; Martin SCUREK; Markéta BÉBAROVÁ; Kristián BRAT; Jan PŘIBYL; Zdeněk STÁREK a Vladimír ROTREKL. Arrhythmogenic Potential of Aminophylline and Its Modulation by Salbutamol: Insights from Human Pluripotent Stem Cell-Derived Cardiomyocytes. In The 49th Annual Meeting of the ESC Working Group on Cardiac Cellular Electrophysiology (EWGCCE). 2025.

@proceedings{2508640,
   author = {Pešl, Martin and Klimovic, Vrana and Beckerová, Deborah and Kabanov, Daniil and Scurek, Martin and Bébarová, Markéta and Brat, Kristián and Přibyl, Jan and Stárek, Zdeněk and Rotrekl, Vladimír},
   booktitle = {The 49th Annual Meeting of the ESC Working Group on Cardiac Cellular Electrophysiology (EWGCCE)},
   keywords = {Aminophylline;Salbutamol;Cardiac electrophysiology;Arrhythmia;hPSC-derived cardiomyocytes;Atomic force microscopy;Multielectrode array},
   language = {eng},
   title = {Arrhythmogenic Potential of Aminophylline and Its Modulation by Salbutamol: Insights from Human Pluripotent Stem Cell-Derived Cardiomyocytes},
   url = {https://escardio.sharepoint.com/:b:/s/ESCEvents/Ee9SJmXW8tNLtZWLcuqZgm8B-gB8FuGEl-ULDsMlPn8rSw},
   year = {2025}
}

TY  - CONF
ID  - 2508640
AU  - Pešl, Martin - Klimovic, Vrana - Beckerová, Deborah - Kabanov, Daniil - Scurek, Martin - Bébarová, Markéta - Brat, Kristián - Přibyl, Jan - Stárek, Zdeněk - Rotrekl, Vladimír
PY  - 2025
TI  - Arrhythmogenic Potential of Aminophylline and Its Modulation by Salbutamol: Insights from Human Pluripotent Stem Cell-Derived Cardiomyocytes
KW  - Aminophylline;Salbutamol;Cardiac electrophysiology;Arrhythmia;hPSC-derived cardiomyocytes;Atomic force microscopy;Multielectrode array
UR  - https://escardio.sharepoint.com/:b:/s/ESCEvents/Ee9SJmXW8tNLtZWLcuqZgm8B-gB8FuGEl-ULDsMlPn8rSw
N2  - Cardiac side effects of pulmonary drugs are well-documented in clinical practice, with aminophylline, a methylxanthine bronchodilator, and salbutamol, a beta-2 adrenergic receptor agonist, both being associated with proarrhythmic effects. However, data on their direct impact on cardiac electrophysiology and contractility, particularly in combination, remain limited. Purpose: This study aimed to investigate the effects of aminophylline and salbutamol, both individually and in combination, on cardiac function using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and HL-1 cardiomyocytes. Methods: Beat rate (BR) and contraction force (CF) were assessed in hPSC-CMs using atomic force microscopy (AFM), while multielectrode array (MEA) recordings and calcium imaging were used to evaluate electrophysiological changes in HL-1 cardiomyocytes. Results: Aminophylline significantly increased BR, CF, and the frequency of rhythm irregularities in both hPSCCMs and HL-1 cardiomyocytes. Notably, calcium sparks were significantly elevated in HL-1 cardiomyocytes at 512 µM aminophylline, supporting its arrhythmogenic potential. In contrast, the combination of aminophylline and salbutamol exhibited a synergistic chronotropic and inotropic effect, while salbutamol mitigated aminophylline-induced arrhythmias. This protective effect is likely mediated via endothelial nitric oxide synthase activation through beta-2 adrenergic receptors. Conclusion: While aminophylline alone poses a significant risk of arrhythmias, its co-administration with salbutamol may enhance cardiovascular safety by reducing its proarrhythmic effects. These findings provide new insights into the cardiac safety of bronchodilator therapy and highlight the potential of hPSC-CM-based AFM platforms for evaluating direct drug effects on cardiac function
ER  -

PEŠL, Martin; Vrana KLIMOVIC; Deborah BECKEROVÁ; Daniil KABANOV; Martin SCUREK; Markéta BÉBAROVÁ; Kristián BRAT; Jan PŘIBYL; Zdeněk STÁREK a Vladimír ROTREKL. Arrhythmogenic Potential of Aminophylline and Its Modulation by Salbutamol: Insights from Human Pluripotent Stem Cell-Derived Cardiomyocytes. In \textit{The 49th Annual Meeting of the ESC Working Group on Cardiac Cellular Electrophysiology (EWGCCE)}. 2025.

Přehled o publikaci