Key result
In human iPSC-derived cardiomyocytes, erythromycin at concentrations of 15-45 μM substantially decreased the maximum capture rate by up to 28% (p < 0.05) and increased the probability of re-entry.
Why the study?
The mechanism underlying erythromycin's cardiotoxic effect and its role in inducing arrhythmias, especially in multicellular cardiac experimental models, remain unclear.
Does erythromycin alter conduction velocity, maximum capture rate, and re-entry formation in human iPSC-derived cardiomyocytes and NRVMs?
Does erythromycin alter conduction velocity, maximum capture rate, and re-entry formation in human iPSC-derived cardiomyocytes and NRVMs?
Effect estimate: declined up to 28±12%
p-value: p=<0.05
Erythromycin demonstrates a concentration-dependent arrhythmogenic window (15-30 μM) for re-entry formation in human iPSC-derived cardiomyocytes, highlighting its proarrhythmic potential.
Erythromycin warrants QT monitoring in at-risk patients; leaves open its precise role in multicellular arrhythmia induction.
Erythromycin is an antibiotic that prolongs the QT-interval and causes Torsade de Pointes (TdP) by blocking the rapid delayed rectifying potassium current (I Kr ) without affecting either the slow delayed rectifying potassium current (I Ks ) or inward rectifying potassium current (I K1 ). Erythromycin exerts this effect in the range of 1.5 μM–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 < 0.05). 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 to 30 μM) at which the probability of re-entry increased.
No takes yet. Share an insight, caveat, or question.
Podgurskaya et al. (2019) studied Arrhythmia / Torsade de Pointes. Erythromycin vs. Control (baseline) was evaluated on Maximum capture rate (MCR) in human iPSC-derived cardiomyocytes (declined up to 28±12%, p=<0.05). In human iPSC-derived cardiomyocytes, erythromycin at concentrations of 15-45 μM substantially decreased the maximum capture rate by up to 28% (p < 0.05) and increased the probability of re-entry.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: