Pathologic features of adriamycin toxicosis in young pigs: nonskeletal lesions
Van Vleet, J.F.; Greenwood, L.A.; Ferrans, V.J.
American Journal of Veterinary Research 40(11): 1537-1552
1979
ISSN/ISBN: 0002-9645 PMID: 525872 Document Number: 146063
In 10 experiments, 53 castrated male 4-8 wk old weanling pigs were given adriamycin (ADR) i.v. at mean dosages of 0.64, 1.0, 1.6, 3.2 or 6.4 mg/kg per wk at various frequencies for up to 20 wk. Mortalities in pigs given these dosages were 0% after 112 days, 100% after 134 days (survival time was 48-134 days), 91% after 75 days (survival time was 5-75 days), 100% after 28 days (survival time was 23-28 days) and 100% after 14 days (survival time was 10-14 days), respectively. Survival time was prolonged in younger pigs and in pigs given smaller but more frequent dosages of ADR. Characteristic gross and histopathologic alterations of ADR toxicosis were observed in pigs given 1.0, 1.6, 3.2 or 6.4 mg/kg per wk mean dosages. The most frequent lesions were in the alimentary tract, myeloid and lymphoid tissues, skin and perivascular tissues at injection sites. Alimentary tract lesions were mucosal epithelial atrophy, with secondary fibrinonecrotic inflammation in the oral cavity and large intestine. Marked hypoplasia was seen in bone marrow and lymphoid tissues, with frequent terminal hemorrhagic diathesis and septicemia. Several days before death, the pigs developed severe dermatitis over the ventral portion of the abdomen and inner surfaces of the limbs. Perivascular necrosis and cellulitis produced by extravasation of ADR was a frequent complication of treatment. Terminal severe acute pneumonia occurred in most pigs. Pericarditis or cardiomyopathy (or both) developed in 14 pigs given 0.64, 1.0 or 1.6 mg/kg each wk (mean cumulative dosage 520.5 mg/m2 of body surface). Characteristic histopathologic and ultrastructural alterations in affected cardiac muscle cells were vacuolar degeneration, myocytolysis and hyaline necrosis. Nephrotoxicosis also was in pigs with chronic ADR toxicosis. Systemic antibiotic treatment did not prolong survival of ADR-treated pigs in 2 experiments, but did in 1 other experiment. [ADR and other anthracycline antibiotics have been widely accepted as effective antineoplastic chemotherapeutic agents for use in humans. Because of the development of cardiotoxicosis in some patients taking ADR its effect on the pig was studied].