Impact of High-Dose Irradiation on Human iPSC-Derived Cardiomyocytes Using Multi-Electrode Arrays: Implications for the Antiarrhythmic Effects of Cardiac Radioablation

Int J Mol Sci. 2021 Dec 29;23(1):351. doi: 10.3390/ijms23010351.


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.

Keywords: cardiac radioablation; electrophysiological alternation; human induced pluripotent stem cell-derived cardiomyocyte; multielectrode array; radiotherapy.

MeSH terms

  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / therapy*
  • Dose-Response Relationship, Radiation
  • Electrodes
  • Electrophysiological Phenomena / radiation effects
  • Gene Expression Regulation / radiation effects
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Myocytes, Cardiac / radiation effects*
  • Radiofrequency Ablation*
  • Time Factors