Sparing of the Heart Facilitates Recovery From Cardiopulmonary Side Effects After Thoracic Irradiation

Purpose: When irradiating thoracic tumors, dose to the heart or lung has been associated with survival. We previously showed in a rat model that in addition to known side effects such as pericarditis, pneumonitis and fibrosis, heart and/or lung irradiation also impaired diastolic function and increased pulmonary artery pressure. Simultaneous irradiation of both organs strongly intensified these effects. However, the long-term consequences of these interactions are not yet known. Therefore, here, we investigated the long-term effects of combined heart and lung irradiation. Methods and Materials: Different regions of the rat thorax containing the heart and/or 50% of the lungs were irradiated with protons. Respiratory rate (RR) was measured biweekly as an overall parameter for cardiopulmonary function. Echocardiography of the heart was performed at 8, 26, and 42 weeks after irradiation. Tissue remodeling and vascular changes were assessed using Masson trichrome and Verhoeff-stained lung and left ventricle tissue collected at 8 and 42 weeks after irradiation. Results: During the entire experimental period RR was consistently increased after combined heart/lung irradiation. This coincided with persistent effects on lung vasculature and reduced right-ventricle (RV) contraction. In contrast, recovery of RR, pulmonary remodeling and RV contraction was observed after sparing of the heart. These corresponding temporal patterns suggest that the reduction of RV function is related to vascular remodeling in the lung. Conclusions: Combined irradiation of lung and heart leads to an intensified, persistent reduction of cardiopulmonary function. Recovery of the pulmonary vasculature and RV function requires heart sparing.