SU‐E‐T‐312: Development of a Rat Model of Radiation‐Induced Heart Disease Using SACRTD

Abstract

Purpose: In radiotherapy treatment of thoracic and chest wall tumors, the heart may be included (partly/fully) in the radiation field, and as a result patients may develop radiation‐induced heart disease (RIHD) several years after irradiation. There is no method to prevent or reverse RIHD, and biological mechanisms are largely unknown. We developed a model of conformal local heart irradiation in rats and present the first results. Method and materials:A small animal conformal radiation therapy device (SACRTD) was used to irradiate experimental animals. Adult male Sprague‐Dawley rats were exposed to localized heart irradiation with a total dose of 18 Gy. For this purpose, rats were anesthetized with isoflurane and placed in a custom made vertical rat holder. The heart was exposed to 3 fields of 6 Gy each, one AP field and 2 lateral fields. For each field, the heart was visualized with the digital X‐ray imager and placed in the isocenter of the 1.8 cm diameter beam. Hearts and lungs were isolated at time points from 2 hours to 4 days after irradiation, fixed in formalin and processed. Immunohistochemistry was performed to show γH2Ax, a marker for DNA damage caused by oxidative stress, and nitrotyrosine, a marker for protein nitration caused by nitrosative stress.Results: Both γH2Ax staining and nitrotyrosine staining were observed throughout the irradiated hearts, indicating that the whole heart was exposed to radiation. γH2Ax was most prominent at 2 hours after irradiation, as DNA repair is known to start immediately after exposure. Increased nitrotyrosine staining was observed mainly in cardiomyocytes, at all time points after irradiation. Minimal γH2Ax and nitrotyrosine were observed in the lung samples Conclusions: The results showed that the SACRTD is an excellent tool for in‐vivo radiobiological studies. Studies on functional and structural changes in the rat heart after localized irradiation are ongoing.