Vascular response to radiation injury in the rat lung.
Changes in relative left-to-right lung blood flow ratios were followed as an index of vascular radiation injury in left-hemithorax-irradiated Sprague-Dawley rats. Single doses of 11 to 21 Gy gamma radiation resulted in a dose-dependent decrease in relative blood flow to the irradiated lung from 3 to 5 weeks after exposure during the development of pneumonitis. Blood flow returned to near normal by 5 weeks after lower doses (11-13.5 Gy). After a single dose of 15 Gy the left-to-right blood flow ratio recovered to 75% of normal at 12 weeks and leveled off. Following 18 Gy irradiation a second period of reduced flow began 16 weeks after exposure. After 21 Gy irradiation flow to the irradiated side remained low for 1 year after exposure. Rats that received a single dose of 18 Gy to the left hemithorax were also treated with one or two of the following drugs: captopril, cyproheptadine, dexamethasone, diethylcarbamazine, penicillamine, or theophylline. Dexamethasone was most effective at preventing the decrease in blood flow to the irradiated lung when treatment was continued through the pneumonitis period and dose was not tapered until 8 weeks after radiation exposure. All other drugs and drug combinations were, for the most part, virtually ineffective after the pneumonitis period. There was a relatively poor correlation with earlier vascular permeability surface area product studies. This suggests that endothelial damage, as well as damage to other cell types, contributes to the development of post-irradiation fibrosis in the lung.
Peterson
L M
LM
Department of Radiation Biology, University of Washington Medical Center, Seattle 98195.
Evans
M L
ML
Graham
M M
MM
Eary
J F
JF
Dahlen
D D
DD
D000818:Animals; D002216:Captopril / Q000627:therapeutic use; D002588:Cesium Radioisotopes; D003533:Cyproheptadine / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D004049:Diethylcarbamazine / Q000627:therapeutic use; D005720:Gamma Rays; D008168:Lung / Q000098:blood supply / Q000528:radiation effects*; D008297:Male; D010396:Penicillamine / Q000627:therapeutic use; D011652:Pulmonary Circulation / Q000502:physiology / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000503:physiopathology* / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000627:therapeutic use
D002588:Cesium Radioisotopes; D003533:Cyproheptadine; D003907:Dexamethasone; D002216:Captopril; D013806:Theophylline; D010396:Penicillamine; D004049:Diethylcarbamazine