Session Item

Radiation-induced heart disease is a critical concern after radiotherapy (RT) for thoracic and chest wall tumors; however, the biological effects and mechanisms are still unknown. In this study, we investigated dose-responsive functional and pathological changes in rat hearts at 1, 3, and 5 months after high-dose irradiation. Then, we sought to elucidate the underlying mechanisms of myocardial changes induced by high-dose irradiation.

Whole hearts of rats (N=72) were irradiated with a single fraction of 0 (control), 10, 20, or 30 Gy and allocated into three groups according to the follow-up period after RT: baseline, one, three, and five months. During follow-up periods, rats underwent functional evaluation by electrocardiogram (EKG) and echocardiography (Echo) at 4-week intervals. If a rat's body weight decreased by 20% or more, it was considered premature death, and the heart was explanted immediately. Otherwise, all hearts were explanted when each group’s follow-up period was completed. Pathological changes of cardiac structures were evaluated using a light microscope after staining with hematoxylin-eosin, Masson’s trichrome, α-smooth muscle actin, desmin, and connexin-43.

All rats irradiated with 0 or 10 Gy completed their follow-up periods with continuously increasing body weight. However, among rats irradiated with 20 or 30 Gy, half of the rats died prematurely at 8–10 weeks after RT, and the remainder survived until 20 weeks. In pathological review, 20–30 Gy groups showed diffuse inflammation and vacuolization at 4 weeks. Then, at 8 weeks, prominent fibrotic changes and intercalated disc disruptions were observed. Notably, at 20 weeks, some rats demonstrated a reversal of fibrosis (reversed group), while others continued to progress fibrosis (progressive group). Progressive group showed increased E/E’ ratio and decreased end-diastolic volume in Echo. Additionally, progressive group showed bradycardia, complete AV block, and prolonged QT interval in EKG. Meanwhile, reversed group showed no significant changes in both functional and pathological analyses.

Rats irradiated with 20 or 30 Gy showed time-dependent myocardial changes. RT-induced inflammation caused a reactive fibrosis, which could proceed to either a profibrotic course (progressive fibrosis) or an anti-fibrotic course (reversed fibrosis). Therefore, the effects of high-dose irradiation on cardiac injury could be a form of “Remodeling”. With further studies, we hope to find a way to promote reversed remodeling following high-dose irradiation.