Radiation Pneumonitis in Rats and Its Modification by the Angiotensin-Converting Enzyme Inhibitor Captopril Evaluated by High-Resolution Computed Tomography

Abstract

Adult male Sprague-Dawley rats were irradiated to the right hemithorax with a range of total doses delivered in 10 equal daily fractions of 4 MeV X rays. Half of each dose group consumed control feed, and half consumed feed containing the angiotensin-converting enzyme inhibitor captopril (50 mg/kg/day) continuously after the last irradiation. High-resolution computed tomography (CT) of the entire thorax was performed at 4 and 8 weeks after the last irradiation, and the findings with CT were correlated with hemodynamic data, heart weight, and pulmonary histopathology. Rats exposed to 20 or 40 Gy in 10 fractions exhibited no acute changes in right lung density. After 60 Gy in 10 fractions, however, right lung density in rats on the control diet increased significantly at 4 weeks, and then returned to normal at 8 weeks. Captopril-treated rats exposed to 60 Gy/10 fractions did not exhibit this transient increase in right lung density. After 80 Gy/10 fractions, right lung density increased to 0.60-0.65 g/cm3 at 4 weeks regardless of diet. At 8 weeks after 80 Gy/10 fractions, right lung density increased further in rats given the control diet, but decreased to near normal levels in captopril-treated animals. The density of the shielded left lung based on the CT was independent of both contralateral radiation dose and diet. Histological examination of the irradiated lungs indicated that these acute changes detected by CT were associated with the exudative and edematous phases of radiation pneumonitis, and that captopril reduced the severity of these changes. Irradiated (40-80 Gy/10 fractions) animals fed the control diet exhibited a significant increase in central venous and pulmonary artery pressure, and cardiac right ventricular hypertrophy. Captopril prevented or attenuated these hypertensive reactions. These data demonstrate that high-resolution CT can detect radiation reactions in rat lung within 4 weeks after 60 Gy/10 fractions, and that captopril spares these acute changes detected by CT. The mechanism of captopril action is not clear, but may be due in part to a reduction in pulmonary arterial pressure, resulting in less severe edema in the irradiated lung.

Effects of genistein following fractionated lung irradiation in mice

“…Amifostine has been shown to protect against increases in breathing rate, increased plasma TGF-β, and fibrosis but is also known to interfere with chemotherapeutics [124][125][126][127]. Studies of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, such as captopril, have shown significant protection against radiation pneumonitis and fibrosis [128][129][130][131][132][133]. Captopril is believed to reduce the effects of radiation on endothelial cells, fibroblasts and macrophages, and regulate the blood pressure of the pulmonary artery thus lowering edema in the lung.…”

Computed tomography of pulmonary sarcoid-like granulomas induced by complete Freund's adjuvant in rats

“…Less data are available concerning the use of lung CT in smaller animals, for which spatial and contrast resolution are limited. Lung CT, however, has been performed in rats for the evaluation of radiation-induced lung injury, but only lung density was considered, and radiological patterns were not precisely described [12,18,19]. In the present study, it was demonstrated that dual-helical lung CT is efficient for the detection of pulmonary sarcoid-like granulomas in the rats injected with CFA.…”

“…Measurement of the mean lung density has previously been used to study radiation induced lung injury in rats [12,18,19]. This index, however, is relatively crude and results can be influenced by many factors, including the lung area scanned and the age of the animal [22].…”

Relationship between Radiation Pneumonitis and Prognosis in Patients with Primary Lung Cancer Treated by Radiotherapy

“…Recently, it has been shown that protective effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (AII) type 1 receptor blocker from RP is a topic of considerable interest [14,23]. Several groups reported that ACE inhibitors especially captopril and AII type 1 receptor blocker were effective in protecting lungs from RP and the development of lung fibrosis in rat radiation injury [30][31][32]. The possibility remains that administration of ACE inhibitors and AII type 1 receptor blocker might have two beneficial effects: control of radiation-induced side effects and control of hypertension in the future.…”