Pretreatment with ICRF-187 provides long-lasting protection against chronic daunorubicin cardiotoxicity in rabbits

Summary 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.