Effects of salbutamol and ipratropium on human stem-cells derived cardiomyocytes’ function

Abstract

Introduction: Patients with obstructive pulmonary diseases are treated by beta-2-agonists, parasympatholytics, and methylxanthines for long periods. Chronic use of these drugs may result in impairment of the cardiovascular system. Direct effects of these bronchodilators on the function of human cardiomyocytes are described insufficiently.

Aims: We aimed to investigate in vitro effects of salbutamol and ipratropium on human-induced pluripotent stem cell-derived cardiomyocyte (hiPS-CMs) cell clusters. We focused on their chronotropic and inotropic effects.

Methods: The measurements of 3D clusters of hiPS-CMs, embryoid bodies (EBs), with spontaneous pacing and contraction abilities were performed using atomic force microscopy (AFM). AFM enables real-time monitoring of EBs’ beating frequency and is capable of measuring its contractility. We measured the effect of increasing concentrations of salbutamol and ipratropium on EBs.

Results: We treated 25 EBs with salbutamol and compared results with the control group of 11 EBs. Similarly, we tested 11 EBs with ipratropium. We observed significant positive chronotropic and inotropic effects in higher concentrations of salbutamol with statistically significant elevation of contraction force for clinically relevant salbutamol concentration. Measurements with ipratropium did not reveal any changes in EBs’ electromechanical function.

Conclusions: The effect of pulmonary drugs on the cardiovascular system can be reliably tested using a combination of AFM and hiPS-CMs. The clinically relevant concentration of salbutamol causes a significant elevation of human cardiomyocytes’ contractility and beating frequency.

Supported by grant MH CZ No NU20-06-00156.