Impact of high-dose irradiation on human ipsc-derived cardiomyocytes using multi-electrode arrays: Implications for the antiarrhythmic effects of cardiac radioablation

Jae Sik Kim, Seong Woo Choi, Yun Gwi Park, Sung Joon Kim, Chang Heon Choi, Myung Jin Cha, Ji Hyun Chang

Research output: Contribution to journalArticlepeer-review

Abstract

Cardiac radioablation is emerging as an alternative option for refractory ventricular ar-rhythmias. 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 cor-rected 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.

Original languageEnglish
Article number351
JournalInternational Journal of Molecular Sciences
Volume23
Issue number1
DOIs
StatePublished - 1 Jan 2022

Keywords

  • Cardiac radioablation
  • Electrophysiological alternation
  • Human induced pluripotent stem cell-derived cardiomyocyte
  • Multielectrode array
  • Radiotherapy

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