Influence of vitamin E and ICRF-187 on chronic doxorubicin cardiotoxicity in miniature swine.

Studies were made of the potential of vitamin E and ICRF-187 to protect against the cardiotoxicity resulting from chronic administration of doxorubicin. Miniature swine (19 to 40 kg) received six injections of doxorubicin (1.6 mg/kg) at 3-week intervals (total dose, 9.6 mg/kg), either alone or concurrently with vitamin E (5000 IU/day for 4 days and 1000 units/day for the next 17 days). In a second study, miniature swine received six injections of doxorubicin (2.4 mg/kg) at 3-week intervals (total dose 14.4 mg/kg), either alone or 30 minutes after 12.5 mg of ICRF-187/kg (intraperitoneally). All animals were sacrificed 3 weeks after the last injection. The frequency and extent of myocardial lesions (vacuolization and myofibrillar loss) were scored on a scale of 0 to 4+. Such lesions were noted in eight of nine pigs given 9.6 mg/kg of doxorubicin alone and in all pigs receiving doxorubicin and vitamin E; however, the severity of the lesions was decreased in the latter animals (average score 1.0, compared with 1.8 in those receiving doxorubicin alone). All swine receiving 14.4 mg/kg of doxorubicin alone developed myocardial lesions (average score, 2.7); these lesions were severe (3+) in four of the animals. In contrast, cardiac lesions were absent in two and minimal (average score, 0.7) in five of the seven animals given 14.4 mg/kg of doxorubicin in combination with ICRF-187.