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 <or=1 year. Survival decreased to <50% by 45 weeks after 12 Gy and by 8-9 weeks after 15 Gy. Captopril (17-56 mg/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 1 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.
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 <or=1 year. Survival decreased to <50% by 45 weeks after 12 Gy and by 8-9 weeks after 15 Gy. Captopril (17-56 mg/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 1 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.
Authors: Agostino Molteni; Lisa F Wolfe; William F Ward; C Hsin Ts'ao; Loredana Brizio Molteni; Patricia Veno; Brian L Fish; Joan M Taylor; Norma Quintanilla; Betty Herndon; John E Moulder Journal: Curr Pharm Des Date: 2007 Impact factor: 3.116
Authors: Meetha Medhora; Feng Gao; Qingping Wu; Robert C Molthen; Elizabeth R Jacobs; John E Moulder; Brian L Fish Journal: Radiat Res Date: 2014-10-31 Impact factor: 2.841
Authors: Terence T Sio; Pamela J Atherton; Levi D Pederson; W Ken Zhen; Robert W Mutter; Yolanda I Garces; Daniel J Ma; James L Leenstra; Jean-Claude M Rwigema; Shaker Dakhil; James D Bearden; Sonja J van der Veen; Apar K Ganti; Steven E Schild; Robert C Miller Journal: Int J Radiat Oncol Biol Phys Date: 2018-11-02 Impact factor: 7.038
Authors: Jean-Claude M Rwigema; Barbara Beck; Wei Wang; Alexander Doemling; Michael W Epperly; Donna Shields; Julie P Goff; Darcy Franicola; Tracy Dixon; Marie-Céline Frantz; Peter Wipf; Yulia Tyurina; Valerian E Kagan; Hong Wang; Joel S Greenberger Journal: Int J Radiat Oncol Biol Phys Date: 2011-04-13 Impact factor: 7.038
Authors: Elizabeth R Jacobs; Jayashree Narayanan; Brian L Fish; Feng Gao; Leanne M Harmann; Carmen Bergom; Tracy Gasperetti; Jennifer L Strande; Meetha Medhora Journal: Health Phys Date: 2019-04 Impact factor: 1.316
Authors: Whitney D Gannon; Michaela R Anderson; Anna J Podolanczuk; Steven M Kawut; Erin D Michos; Vincent Cottin; Michael Kreuter; Ganesh Raghu; R Graham Barr; David J Lederer Journal: Ann Am Thorac Soc Date: 2019-11
Authors: Javed Mahmood; Salomeh Jelveh; Victoria Calveley; Asif Zaidi; Susan R Doctrow; Richard P Hill Journal: Int J Radiat Biol Date: 2011-06-15 Impact factor: 2.694
Authors: Feng Gao; Jayashree Narayanan; Cortney Joneikis; Brian L Fish; Aniko Szabo; John E Moulder; Robert C Molthen; Elizabeth R Jacobs; R Nagarjun Rao; Meetha Medhora Journal: Radiat Res Date: 2013-03-12 Impact factor: 2.841