Integrative physiological study of radiation-induced lung injury: effects on cardiac function and kidney integrity

Radiotherapy is used to treat tumors in the chest, but can cause radiation-induced lung injury (RILI) in 5%-50% of patients. The study investigated changes in lung and heart function and kidney integrity in a model of RILI. Primary outcome was lung compliance at 12 wk. Secondary outcomes included analysis of ventilatory effort, cardiovascular function, and renal integrity. About 30 adult Wistar rats (8-10 wk old, 390 ± 22 g) were randomized into two groups: one received 15 Gray (Gy) of irradiation to the right lung radiation (RLR group, <i>n</i> = 20), whereas control group (CTRL group, <i>n</i> = 10) received no irradiation. After irradiation, echocardiography and chest computed tomography (CT) were performed every 3 wk, whereas respiratory mechanics and right ventricle systolic pressure (RVSP) were assessed at 12 wk. Lung tissue was analyzed for collagen deposition and immunohistochemistry markers, including signal transducer and activator of transcription-3 (STAT-3) and transforming growth factor-beta (TGF-β). Kidney tissue was evaluated for tubular cell spacing and collagen deposition. In RLR, compared with CTRL group, lung compliance reduced (0.24 ± 0.02 mL·cmH₂O^-1 vs. 0.29 ± 0.03 mL·cmH₂O^-1; <i>P</i> = 0.039), whereas respiratory effort increased. CT analysis demonstrated progressive left lung volume expansion over time. Radiation exposure increased lung macrophages, arterial wall thickness, fibroblast proliferation, and collagen deposition in peripheral and perivascular regions (<i>P</i> < 0.001). Moreover, both STAT-3- and TGF-β - positive cells were increased in lung parenchyma. Pulmonary hypertension developed, detected by echocardiography and confirmed by invasive RVSP measurement. RLR group exhibited increased kidney collagen deposition and tubular cell thickening (<i>P</i> = 0.002). These findings demonstrate the systemic impact of radiation on cardiorespiratory function and kidney integrity.<b>NEW & NOTEWORTHY</b> Radiotherapy is used to treat chest tumors, but may induce radiation-induced lung injury (RILI) in some patients. In the current RILI model, significant changes were observed in both irradiated and nonirradiated lungs. Increased right ventricle afterload and kidney morphological alterations were detected, suggesting vascular congestion. This study highlights the well-known impact of RILI on lungs but also emphasizes the often-overlooked effects on heart and kidneys in clinical practice.