Arrhythmic events in clustered human pluripotent stem cell-derived cardiomyocytes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F21%3A00120105" target="_blank" >RIV/00216224:14110/21:00120105 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.termis-workshop2021.cz/" target="_blank" >https://www.termis-workshop2021.cz/</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Arrhythmic events in clustered human pluripotent stem cell-derived cardiomyocytes

Popis výsledku v původním jazyce

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&amp;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.

Název v anglickém jazyce

Arrhythmic events in clustered human pluripotent stem cell-derived cardiomyocytes

Popis výsledku anglicky

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&amp;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.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

<a href="/cs/project/NU20-06-00156" target="_blank" >NU20-06-00156: Vliv pneumologické medikace na funkce lidských kardiomyocytů.</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů