期刊
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
卷 75, 期 5, 页码 1528-1536出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ijrobp.2009.07.1743
关键词
Radiation injury; mitigation; lung function; angiotensin-converting enzyme inhibitors; ACE
资金
- National Institutes of Health/National Institute of Allergy and Infectious Diseases [U19-Al-67734, RC-1 AI 81294]
Purpose: To find the mitigators of pneumonitis induced by moderate doses of thoracic radiation (10-15 Gy). Methods and Materials: Unanesthetized WAG/RijCmcr female rats received a single dose of X-irradiation (10, 12, or 15 Gy at 1.615 Gy/min) to the thorax. Captopril (an angiotensin-converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in the drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating the breathing rate, ex vivo vascular reactivity, and histopathologic findings. Survival analysis was undertaken on all animals, except those scheduled for death. Results: Survival after a dose of 10 Gy to the thorax was not different from that of unirradiated rats for <= 1 year. Survival decreased to <50% by 45 weeks after 12 Gy and by 8-9 weeks after 15 Gy. Captopril (17-56mg/kg/d) improved survival and reduced radiation-induced increases in breathing rate, changes in vascular reactivity, and histopathologic evidence of injury. Radiation-induced increases in the breathing rate were prevented even if captopril was started I week after irradiation or if it was discontinued after 5 weeks. Losartan, although effective in reducing mortality, was not as efficacious as captopril in mitigating radiation-induced increases in the breathing rate or altered vasoreactivity. Conclusion: In rats, a moderate thoracic radiation dose induced pneumonitis and morbidity. These injuries were mitigated by captopril even when it was begun 1 week after radiation or if discontinued 5 weeks after exposure. Losartan was less effective in protecting against radiation-induced changes in vascular reactivity or tachypnea. (C) 2009 Elsevier Inc.
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