The long-term protective effect of
ICRF-187 against chronic
daunorubicin cardiotoxicity was examined. Rabbits were given 3.2 mg
daunorubicin/kg, with or without pretreatment with 25 mg
ICRF-187/kg, once every 3 weeks over an 18-week period (6 doses). The experiment was terminated 3 months after the last treatment. At this time, all seven rabbits given
daunorubicin alone had evidence of myocardial alterations ranging from minimal (2 animals) to mild (5 animals). Pretreatment with
ICRF-187 caused a significant reduction in both the incidence and the severity of cardiac lesions. Hearts from the majority (5 of 7) of animals given the combination of
ICRF-187 and
daunorubicin were normal; myocardial alterations were minimal in the remaining rabbits treated with
ICRF-187. In previous studies
ICRF-187 was found to cause a reduction in
cardiotoxicity 1-3 weeks after the final
anthracycline dose. The results of the present study demonstrate that pretreatment with
ICRF-187 provides prolonged protection against the
cardiomyopathy, as opposed to producing only a delay in the appearance of cardiac alterations.