| Abstrakt: |
Skin ulceration caused by extravasation of Adriamycin follows a severely protracted course accompanied by considerable morbidity. To develop an animal model of Adriamycin ulceration, we compared intradermal injection of Adriamycin to injection beneath the panniculus carnosus with varying drug volumes and concentrations. Injections beneath the rat panniculus carnosus caused only irregular ulcerative lesions. Intradermal injection produced predictable, uniform skin necrosis and ulceration. Both increasing volume and increasing concentration of Adriamycin caused proportionate increases in skin ulcer size and in time required for healing. A critical concentration range for Adriamycin necrosis is 0.010--0.020 mg/ml, suggesting that the drug would have to be greatly diluted to reduce clinical skin ulceration. Adriamycin-induced skin necrosis heals at a slower rate than surgically created skin defects of similar size, indicating a reduced rate of wound contraction. Removal of the necrotic skin allows faster healing, although still slower than normal, due to removal of splinting effect. Histology shows early skin necrosis, with acute inflammation developing after 1 week. Epidermal hypertrophy is present at the edges of the necrosis. The small vessels remain patent. Multiple small vesicles of unknown etiology are seen in the necrotic dermis. |
