Arrhythmic events in clustered human pluripotent stem cell-derived cardiomyocytes
|Year of publication
|MU Faculty or unit
|Aminophylline is a methylxanthine bronchodilator with a documented proarrhythmic action. We aimed to describe changes in rhythm pattern of spontaneously beating human pluripotent stem cell-derived cardiomyocytes (hPSC-CM). Moreover the inotropic changes were never before studied in hPSC-CM. Methods: hPSC-CM were differentiated in clusters[1-3] basic biomechanical parameters, such as the average value of contraction force and the beat rate (BR), were assessed by atomic force microscopy (AFM) as previously described[1,2]. Cells were stabilized in Tyrode solution (baseline) and applied were increasing concentrations of aminophylline (10 µM, 100 µM, 1 mM, and 10 mM). Results: the 10mM aminophylline significantly increased beat rate (BR) in comparison with the lower concentrations. There were no significant differences in inotropic effects of aminophylline on the hPSC-CMs between all groups and concentrations. Number of measured clusters underwent atypical arrhythmic pattern - termed "stop&go effect" - presenting as a series of fast BR episodes (the equivalent of tachycardia) followed by inactivity. This effect occurred during aminophylline treatment with various concentrations. Conclusions: an aberrant cardiomyocyte response to aminophylline was observed, suggesting an arrhythmogenic potential of the drug. Our data represent a missing link between the arrhythmic events related to the aminophylline/theophylline treatment in clinical practice and subcellular mechanisms of methylxanthine arrhythmogenesis. AFM combined with hPSC-CM serve as a robust platform for direct drug effects screening.