Abstract:
:Erythromycin is an antibiotic that prolongs the QT-interval and causes Torsade de Pointes (TdP) by blocking the rapid delayed rectifying potassium current (IKr) without affecting either the slow delayed rectifying potassium current (IKs) or inward rectifying potassium current (IK1). Erythromycin exerts this effect in the range of 1.5-100 μM. However, the mechanism of action underlying its cardiotoxic effect and its role in the induction of arrhythmias, especially in multicellular cardiac experimental models, remain unclear. In this study, the re-entry formation, conduction velocity, and maximum capture rate were investigated in a monolayer of human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes from a healthy donor and in a neonatal rat ventricular myocyte (NRVM) monolayer using the optical mapping method under erythromycin concentrations of 15, 30, and 45 μM. In the monolayer of human iPSC-derived cardiomyocytes, the conduction velocity (CV) varied up to 12 ± 9% at concentrations of 15-45 μM as compared with that of the control, whereas the maximum capture rate (MCR) declined substantially up to 28 ± 12% (p < 0.01). In contrast, the tests on the NRVM monolayer showed no significant effect on the MCR. The results of the arrhythmogenicity test provided evidence for a "window" of concentrations of the drug (15-30 μM) at which the probability of re-entry increased.
journal_name
Cardiovasc Toxicoljournal_title
Cardiovascular toxicologyauthors
Podgurskaya AD,Tsvelaya VA,Slotvitsky MM,Dementyeva EV,Valetdinova KR,Agladze KIdoi
10.1007/s12012-019-09532-xsubject
Has Abstractpub_date
2019-12-01 00:00:00pages
518-528issue
6eissn
1530-7905issn
1559-0259pii
10.1007/s12012-019-09532-xjournal_volume
19pub_type
杂志文章abstract::3,4-Methylenedioxymethamphetamine (MDMA), more commonly known as "ecstasy," is a semi-synthetic entactogenic phenylethylamine. In recent years it has gained popularity as a recreational drug whose use has registered an upward trend especially among adolescents and young adults. Despite its unwarranted reputation of be...
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journal_title:Cardiovascular toxicology
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journal_title:Cardiovascular toxicology
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