title: Corticosteroids prevent acute lung dysfunction caused by thoracic irradiation in unanesthetized sheep.
abstract: We sought to determine the effect of corticosteroid therapy in a new acute model of oxidant lung injury, thoracic irradiation in awake sheep. Sheep were irradiated with 1,500 rads to the whole chest except for blocking the heart and adjacent ventral lung. Seven experimental sheep were given methylprednisolone (1 g intravenously every 6 h for four doses) and thoracic irradiation; control sheep received only irradiation. In irradiated control sheep, lung lymph flow increased from baseline (7.6 ml/h) to peak at 3 h (13.2), and lung lymph protein clearance increased from 5.1 to 9.7 ml/h. Mean pulmonary artery pressure increased in the irradiated control sheep from 19 to 32.4 cm H2O, whereas the lung lymph thromboxane concentration increased from 0.09 to 6.51 ng/ml at 3 h. Arterial oxygen tension in irradiated control sheep fell gradually from 86 mm Hg at baseline to 65 mm Hg at 8 h. Methylprednisolone administration significantly prevented the increase in lung lymph protein clearance, mean pulmonary artery pressure, and lung lymph thromboxane concentration. Methylprednisolone also prevented the fall in arterial oxygen tension after thoracic irradiation, but did not prevent a further decrease in lymphocytes in blood or lung lymph after radiation. We conclude that corticosteroid therapy prevents most of the acute physiologic changes caused by thoracic irradiation in awake sheep.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
authors.forename: J E
authors.initials: JE
authors.lastname: Loyd
authors.forename: J M
authors.initials: JM
authors.lastname: Bolds
authors.forename: N
authors.initials: N
authors.lastname: Wickersham
authors.forename: A W
authors.initials: AW
authors.lastname: Malcolm
authors.forename: K L
authors.initials: KL
authors.lastname: Brigham
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D001772:Blood Cell Count; D001784:Blood Gas Analysis; D006439:Hemodynamics; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000209:etiology*; D008196:Lymph / Q000166:cytology / Q000378:metabolism; D008775:Methylprednisolone / Q000627:therapeutic use*; D011506:Proteins / Q000378:metabolism; D011651:Pulmonary Artery / Q000503:physiopathology; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D012756:Sheep; D013909:Thorax / Q000528:radiation effects*; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D011506:Proteins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D008775:Methylprednisolone