Radioprotective and hemodynamic effects of WR-2721 and cystamine in rats: time course studies

In experiments on rats radioprotective dose of WR-2721 (200 mg/kg) and cystamine (50 mg/kg) exhibited significant protective effects against radiation death during the first hour after their i. m. administration. Gamma rays were delivered with the dose rate of 0.35-0.31 Gy/min in gradually increased doses for the calculation of LD values and relative efficacy of the whole body irradiation. WR-2721 afforded protection with the highest dose reduction factor (DRF) of 1.51, while the best DRF value after cystamine was 1.36. No protection was found when the interval between injection of both protectors and the beginning of irradiation was longer than 60 min. WR-2721 as well as cystamine induced in pentobarbital anesthetized rats significant depression of cardiac output, hypotension and bradycardia immediately after their i. m. injections. The signs of depression of the hemodynamics persisted throughout the 4-hour observation period. Our results indicate that the hemodynamic effects of WR-2721 and of cystamine are not important for their radioprotective actions in rats.