Feasibility study evaluating arrhythmogenesis and cardiac damage after heart-base irradiation in mice: A brief...

Radiation-induced heart disease (RIHD) is a potential cause of morbidity and mortality in dogs undergoing thoracic irradiation. Arrhythmias and sudden death have been documented in dogs undergoing stereotactic body radiation therapy for heart base tumours. A study was proposed to interrogate the effect of different stereotactic-like radiation prescriptions on RIHD development, including arrhythmogenesis and classical histological endpoints in a mouse model. A pilot study was performed initially. The heart base of CD1 (n = 3) and C57Bl/6J (n = 3) female mice were irradiated (12 Gy × 3, daily) with a clinical linear accelerator. No significant adverse effects were noted and each mouse survived the entire subsequent 3-month observation period. At various time points, no arrhythmias were identified on ECG analysis. Cardiac histology (haematoxylin and eosin, and picrosirius red staining) was performed at 3 months. In a single CD1 mouse and two C57BI/6J mice, multifocal, minimal, peri-vascular lymphoplasmacytic inflammation was noted within the irradiated proximal heart. In one mouse of each strain, a small, single focus of fibrinoid vascular necrosis was observed. Overall, there was no significant myocardial necrosis, atrophy or inflammation. Picrosirius red staining revealed no evidence of fibrosis in any mouse. Dosimetric verification indicated that the irradiation was successful and delivered as planned, with an average predicted-to-measured dose-difference within 5%. While this study did not demonstrate significant arrhythmogenesis, certain modifications of the experimental mouse irradiation procedures are discussed which may enable more translationally relevant modelling of the canine cardiac response to SBRT-like irradiation.