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Salbutamol attenuates arrhythmogenic effect of aminophylline in a hPSC-derived cardiac model

D. Kabanov, S. Vrana Klimovic, D. Beckerová, M. Molcan, M. Scurek, K. Brat, M. Bebarova, V. Rotrekl, J. Pribyl, M. Pesl

. 2024 ; 14 (1) : 27399. [pub] 20241109

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25003489

Grantová podpora
A4L_ACTIONS 964997 Horizon 2020
A4L_ACTIONS 964997 Horizon 2020
A4L_ACTIONS 964997 Horizon 2020
and CIISB, Instruct-CZ Centre of Instruct-ERIC EU consortium LM2023042 Ministerstvo Školství, Mládeže a Tělovýchovy
and CIISB, Instruct-CZ Centre of Instruct-ERIC EU consortium LM2023042 Ministerstvo Školství, Mládeže a Tělovýchovy
MUNI/A/1547/2023 Ministerstvo Školství, Mládeže a Tělovýchovy
MUNI/A/1547/2023 Ministerstvo Školství, Mládeže a Tělovýchovy
MUNI/A/1547/2023 Ministerstvo Školství, Mládeže a Tělovýchovy
and CIISB, Instruct-CZ Centre of Instruct-ERIC EU consortium LM2023042 Ministerstvo Školství, Mládeže a Tělovýchovy
MUNI/A/1547/2023 Ministerstvo Školství, Mládeže a Tělovýchovy
UP CIISB" (No. CZ.02.1.01/0.0/0.0/18_046/0015974), European Regional Development Fund
UP CIISB" (No. CZ.02.1.01/0.0/0.0/18_046/0015974), European Regional Development Fund
UP CIISB" (No. CZ.02.1.01/0.0/0.0/18_046/0015974), European Regional Development Fund
NU20-06-001 Ministerstvo Zdravotnictví Ceské Republiky
NU20-06-001 Ministerstvo Zdravotnictví Ceské Republiky
NU20-06-001 Ministerstvo Zdravotnictví Ceské Republiky
NU20-06-001 Ministerstvo Zdravotnictví Ceské Republiky
NU20-06-001 Ministerstvo Zdravotnictví Ceské Republiky
NU20-06-001 Ministerstvo Zdravotnictví Ceské Republiky
A4L_Bridge101136453 HORIZON EUROPE European Research Council
MUQUABIS GA no. 101070546 HORIZON EUROPE European Research Council
A4L_Bridge101136453 HORIZON EUROPE European Research Council
A4L_Bridge101136453 HORIZON EUROPE European Research Council
EXCELES, No. LX22NPO5104 HORIZON EUROPE Framework Programme
EXCELES, No. LX22NPO5104 HORIZON EUROPE Framework Programme

The combination of aminophylline and salbutamol is frequently used in clinical practice in the treatment of obstructive lung diseases. While the side effects (including arrhythmias) of the individual bronchodilator drugs were well described previously, the side effects of combined treatment are almost unknown. We aimed to study the arrhythmogenic potential of combined aminophylline and salbutamol treatment in vitro. For this purpose, we used the established atomic force microscopy (AFM) model coupled with cardiac organoids derived from human pluripotent stem cells (hPSC-CMs). We focused on the chronotropic, inotropic, and arrhythmogenic effects of salbutamol alone and aminophylline and salbutamol combined treatment. We used a method based on heart rate/beat rate variability (HRV/BRV) analysis to detect arrhythmic events in the hPSC-CM based AFM recordings. Salbutamol and aminophylline had a synergistic chronotropic and inotropic effect compared to the effects of monotherapy. Our main finding was that salbutamol reduced the arrhythmogenic effect of aminophylline, most likely mediated by endothelial nitric oxide synthase activated by beta-2 adrenergic receptors. These findings were replicated and confirmed using hPSC-CM derived from two cell lines (CCTL4 and CCTL12). Data suggest that salbutamol as an add-on therapy may not only deliver a bronchodilator effect but also increase the cardiovascular safety of aminophylline, as salbutamol reduces its arrhythmogenic potential.

Citace poskytuje Crossref.org

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$a The combination of aminophylline and salbutamol is frequently used in clinical practice in the treatment of obstructive lung diseases. While the side effects (including arrhythmias) of the individual bronchodilator drugs were well described previously, the side effects of combined treatment are almost unknown. We aimed to study the arrhythmogenic potential of combined aminophylline and salbutamol treatment in vitro. For this purpose, we used the established atomic force microscopy (AFM) model coupled with cardiac organoids derived from human pluripotent stem cells (hPSC-CMs). We focused on the chronotropic, inotropic, and arrhythmogenic effects of salbutamol alone and aminophylline and salbutamol combined treatment. We used a method based on heart rate/beat rate variability (HRV/BRV) analysis to detect arrhythmic events in the hPSC-CM based AFM recordings. Salbutamol and aminophylline had a synergistic chronotropic and inotropic effect compared to the effects of monotherapy. Our main finding was that salbutamol reduced the arrhythmogenic effect of aminophylline, most likely mediated by endothelial nitric oxide synthase activated by beta-2 adrenergic receptors. These findings were replicated and confirmed using hPSC-CM derived from two cell lines (CCTL4 and CCTL12). Data suggest that salbutamol as an add-on therapy may not only deliver a bronchodilator effect but also increase the cardiovascular safety of aminophylline, as salbutamol reduces its arrhythmogenic potential.
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