Key result
High-dose irradiation reversibly alters human iPSC-derived cardiomyocyte conduction with recovery within ~6 hours.
Why the study?
Cardiac radioablation is emerging for refractory ventricular arrhythmias, but the immediate acute effect of high-dose irradiation on human cardiomyocytes remains poorly known.
Does high-dose irradiation modify the electrical activities and gene expression of human iPSC-derived cardiomyocytes?
Does high-dose irradiation modify the electrical activities and gene expression of human iPSC-derived cardiomyocytes?
High-dose irradiation immediately and reversibly modifies the electrical conduction of human iPSC-derived cardiomyocytes, suggesting cellular compensatory mechanisms may contribute to the antiarrhythmic effects of cardiac radioablation.
Reversible conduction changes in vitro warrant dosing caution; leaves open whether compensatory mechanisms explain clinical radioablation effects.
Cardiac radioablation is emerging as an alternative option for refractory ventricular arrhythmias. However, the immediate acute effect of high-dose irradiation on human cardiomyocytes remains poorly known. We measured the electrical activities of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) upon irradiation with 0, 20, 25, 30, 40, and 50 Gy using a multi-electrode array, and cardiomyocyte function gene levels were evaluated. iPSC-CMs showed to recover their electrophysiological activities (total active electrode, spike amplitude and slope, and corrected field potential duration) within 3–6 h from the acute effects of high-dose irradiation. The beat rate immediately increased until 3 h after irradiation, but it steadily decreased afterward. Conduction velocity slowed in cells irradiated with ≥25 Gy until 6–12 h and recovered within 24 h; notably, 20 and 25 Gy-treated groups showed subsequent continuous increase. At day 7 post-irradiation, except for cTnT, cardiomyocyte function gene levels increased with increasing irradiation dose, but uniquely peaked at 25–30 Gy. Altogether, high-dose irradiation immediately and reversibly modifies the electrical conduction of cardiomyocytes. Thus, compensatory mechanisms at the cellular level may be activated after the high-dose irradiation acute effects, thereby, contributing to the immediate antiarrhythmic outcome of cardiac radioablation for refractory ventricular arrhythmias.
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Kim et al. (2021) studied Refractory ventricular arrhythmias. High-dose irradiation vs. 0 Gy was evaluated on Electrical activities (total active electrode, spike amplitude and slope, corrected field potential duration, beat rate, conduction velocity) and cardiomyocyte function gene levels. High-dose irradiation (20-50 Gy) immediately and reversibly modified the electrical conduction of human iPSC-derived cardiomyocytes, with electrophysiological recovery within 3-6 hours.
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