Effects of amifostine on radiation-induced cardiac damage.
The purpose of this study was to investigate whether administration of amifostine prior to irradiation could reduce radiation damage of the rat heart. Female Spraque-Dawley rats were randomized to receive single-dose irradiation (0-22.5 Gy) locally to the heart. Fifteen to twenty minutes before radiation exposure, the animals received either intraperitoneally administered amifostine (160 mg/kg) or buffered saline solution. At 6 months post-irradiation, cardiac function was assessed by the in vitro working rat heart preparation. The severity of interstitial and/or perivascular fibrosis in different anatomical regions of the rat heart was assessed using a semi-quantitative scoring system. Radiation exposure to doses > or = 20 Gy markedly reduced coronary flow, aortic flow and cardiac output. Administration of amifostine prior to radiotherapy afforded protection against these effects and normal cardiac output was maintained, even after 22.5 Gy. A small, non-significant, reduction in histological damage (i.e. perivascular fibrosis and interstitial fibrosis) was also apparent in animals treated with amifostine. There was a clear protective effect of amifostine on the severity and extent of macroscopic damage in lung tissue included in the cardiac irradiation field. The findings of this study suggest that a single dose of amifostine administered prior to irradiation is effective in reducing cardiac damage.
Kruse
Jacqueline J C M
JJ
Leiden University Medical Centre, Department of Clinical Oncology, Leiden, The Netherlands. jkruse@nki.nl
Strootman
Erwin G
EG
Wondergem
Jan
J
D004999:Amifostine / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects / Q000528:radiation effects; D003326:Coronary Circulation / Q000528:radiation effects; D004341:Drug Evaluation; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000528:radiation effects*; D009206:Myocardium / Q000473:pathology; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
D011837:Radiation-Protective Agents; D004999:Amifostine