Purpose To find mitigators of pneumonitis induced by moderate doses of thoracic radiation (10–15 Gy). Materials and Methods Unanesthetized WAG/RijCmcr female rats received single doses of X-irradiation (10, 12 or 15 Gy at 1.615 Gy/minute) to the thorax. Captopril (an angiotensin converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating breathing rate, ex vivo vascular reactivity and histopathology. Survival analysis was undertaken on all animals except those scheduled for sacrifice. Results Survival following a dose of 10 Gy to the thorax was not different from unirradiated rats up to one year. Survival decreased to less than 50%, by 45 weeks after 12 Gy and by 8–9 weeks after 15 Gy. Captopril (17–56 mg/kg/day) improved survival and reduced radiation-induced increases in breathing rate, changes in vascular reactivity and histopathological evidence of injury. Radiation-induced increases in breathing rate were prevented even if captopril was started 1 week following irradiation or if it was discontinued after 5 weeks. Losartan, though effective in reducing mortality was not as efficacious as captopril in mitigating radiation-induced increases in breathing rate or altered vasoreactivity. Conclusions In rats, a moderate thoracic dose of radiation induced pneumonitis and morbidity. These injuries were mitigated by captopril even when it was commenced 1 week after irradiation or if discontinued after 5 weeks following exposure. Losartan was less effective in protecting against radiation-induced changes in vascular reactivity or tachypnea.

PurposeTo study vascular injury following whole thoracic irradiation with single sublethal doses of X-rays in the rat and to develop markers that might predict severity of injury. Materials and MethodsRats after 5 or 10 Gy thorax only irradiation and age-matched controls were studied at 3 days, 2 weeks, 1, 2, 5 and 12 months. Several pulmonary NOT THE PUBLISHED VERSION; this is the author's final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page. Oncology -Biology -Physics, Vol. 74, No. 1 (May 2009): pg. 192-199. DOI. This article is © Elsevier and permission has been granted for this version to appear in e-Publications@Marquette. Elsevier does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from Elsevier. International Journal of Radiation3 vascular parameters were evaluated, including hemodynamics, vessel density, total lung angiotensin converting enzyme activity and right ventricular hypertrophy. ResultsBy 1 month, rats in the 10 Gy group had pulmonary vascular dropout, right ventricular hypertrophy, increased pulmonary vascular resistance, increased dry lung weights, and decreases in total lung angiotensin converting enzyme activity as well as pulmonary artery distensibility. On the other hand irradiation with 5 Gy resulted only in a modest increase in right ventricular weight and a reduction in lung angiotensin converting enzyme activity. ConclusionsIn a previous investigation employing the same model we observed that there was recovery from radiation induced attenuation of pulmonary vascular reactivity. In this study we report that there is deterioration in several vascular parameters up to 1 year following exposure to 10 Gy suggesting sustained remodeling of the pulmonary vasculature. Our data support clinically relevant injuries which appear in a time and dose related manner after exposure to relatively low doses of radiation.

Purpose-To characterize structural and functional injuries following a single dose of whole-thorax irradiation that might be survivable after a nuclear attack/accident.Methods-Rats were exposed to 5 or 10 Gy of X-rays to the whole thorax with other organs shielded. Non-invasive measurements of breathing rate and arterial oxygen saturation, and invasive evaluations of bronchoalveolar lavage fluid, (for total protein, Clara cell secretory protein), vascular reactivity and histology were conducted for at least 6 time points up to 52 wks after irradiation.Results-Irradiation with 10 Gy resulted in increased breathing rate, a reduction in oxygen saturation, an increase in bronchoalveolar lavage fluid protein and attenuation of vascular reactivity between 4-12 wks after irradiation. These changes were not observed with the lower dose of 5 Gy. Histological examination revealed perivascular edema at 4-8 wks after exposure to both doses, and mild fibrosis beyond 20 wks after 10 Gy.Conclusions-Single-dose exposure of rat thorax to 10 but not 5 Gy X-irradiation resulted in a decrease in oxygen uptake and vasoreactivity and an increase in respiratory rate, which paralleled early pulmonary vascular pathology. Vascular edema resolved and was replaced by mild fibrosis beyond 20 wks after exposure, while lung function recovered.

The goal of these studies was to characterize the infiltrating inflammatory cells during pneumonitis caused by moderate doses of radiation. Two groups of male rats (WAG/RijCmcr, 8 weeks old) were treated with single 10-or 15-Gy doses of thoracic X radiation; a third group of age-matched animals served as controls. Only 25% rats survived the 15-Gy dose. Bronchoalveolar lavage fluid and whole lung mounts were subjected to cytological and histological evaluation after 8 weeks for distribution of resident macrophages, neutrophils, lymphocytes and mast cells. There was a modest increase in airway and airspace-associated neutrophils in lungs from rats receiving 15 Gy. Mast cells (detected by immunohistochemistry for tryptase) increased over 70% with 10 Gy and over 13-fold after 15 Gy, with considerable leakage of tryptase into blood vessels and airways. Circulating levels of eight inflammatory cytokines were not altered after 10 Gy but appeared to decrease after 15 Gy. In summary, there were only modest increases in cellular inflammatory infiltrate during pneumonitis after a non-lethal dose of 10 Gy, but there was a dramatic rise in mast cell infiltration after 15 Gy, suggesting that circulating levels of mast cell products may be useful markers of severe pneumonitis.

No abstract