Introduction

Salbutamol and aminophylline are frequent therapies in obstructive lung diseases. The effect of isolated molecules on cardiomyocytes was described previously. Combined effect of these molecules is unknown from human models.

Aims

We aimed to examine combined in vitro effect of salbutamol and aminophylline on clusters of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) with emphasis on chronotropic and inotropic effect.

Methods

We measured in vitro effect of clinically relevant concentrations of salbutamol alone and combination of salbutamol/aminophylline on 3D clusters of spontaneously beating hiPS-CMs, using atomic force microscopy (AFM). Contraction forces, beat rates and interbeat intervals were recorded/calculated and statistically evaluated for 10 nM, 100 nM, 1 µM and 10 µM concentrations of salbutamol alone and multivariants of combined treatment with aminophylline (10 nM, 100 nM, 1 µM) and salbutamol (10 µM, 100 µM and 1mM).

Results

A total of 74 cardiomyocyte clusters were treated with salbutamol, aminophylline, their combination or served as controls. Salbutamol alone had a concentration-dependent positive inotropic effect and its increasing concentrations positively correlated with increased beat rate (the differences being insignificant). Combinations of aminophylline and salbutamol had both positive inotropic and chronotropic effect. In contrary, beat rate variability (= in vitro correlate of arrhythmogenic effect) decreased with combined treatment compared to aminophylline alone.

Conclusion

Salbutamol appears to have protective effect on arrhythmogenicity in combination with aminophylline. Supported by grant No MH CZ NU20-06-00156.