REDUCTION OF CHRONIC DAUNORUBICIN CARDIOTOXICITY BY ICRF-187 IN RABBITS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 31  (1) , 85-97
Abstract
To determine whether ICRF-187 (NSC-169780) [(+)-(S)-razoxane] would alter chronic daunorubicin (NSC-82151) cardiac toxicity, male New Zealand rabbits were given 3.2 mg/kg of daunorubicin i.v. alone or 30 min after 12.5 or 25.0 mg/kg of ICRF-187 i.p. at 3 wk intervals. Control rabbits received either saline i.v. or ICRF-187 (12.5 or 25.0 mg/kg) i.p. on the same schedule. Three weeks after the 5th injection, the animals were sacrificed. The frequency and extent of cellular alterations were graded on a scale of 0-4. Lesions consisting mainly of vacuolization and myofibrillar loss were noted in the hearts of all 12 rabbits given daunorubicin alone. The severity ranged from 1-3 (average 1.8). No abnormalities were noted in 1 of 5 (12.5 mg/kg) and 3 of 7 (25.0 mg/kg) ICRF-treated rabbits. The remaining 8 hearts from both pretreatment groups displayed minimal alterations ranging from 0.5-1.0 (average 0.9). Concurrent administration of the antineoplastic agent ICRF-187 may offer a means of reducing chronic daunorubicin cardiac toxicity.