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.

• Klíčová slova
• Aminophylline, Arrhythmogenic effects, Atomic force microscopy, iPSC, Biomechanical properties, Cardiomyocytes, Drug cardiotoxicity, HESC, Pulmonary drug screening, Salbutamol,
• MeSH
• albuterol * farmakologie   MeSH
• aminofylin * farmakologie   MeSH
• bronchodilatancia farmakologie   MeSH
• buněčné linie MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• lidé MeSH
• mikroskopie atomárních sil MeSH
• pluripotentní kmenové buňky účinky léků   cytologie   MeSH
• srdeční arytmie * farmakoterapie   MeSH
• srdeční frekvence účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• albuterol * MeSH
• aminofylin * MeSH
• bronchodilatancia MeSH