title: Mediation of subacute anthracycline cardiotoxicity in rabbits by cardiac histamine release.
abstract: We tested the hypothesis that cardiac histamine release mediates subacute doxorubicin (DXR) cardiotoxicity in rabbits. New Zealand white rabbits given DXR 20 mg/kg i.v. over 30 min developed myocardial damage 24 h later that was similar to that observed in humans. In isolated heart preparations, DXR produced dose-related cardiac histamine release at DXR concentrations of 1, 5, and 25 micrograms/ml given as 1-min exposures. Prior exposure of isolated hearts to 10 microM cromolyn sodium completely prevented histamine release from 5 micrograms/ml DXR. Pretreatment of animals with cromolyn produced significant protection against DXR-mediated subacute cardiotoxicity. We conclude that the release of cardiac histamine may be involved in the pathogenesis of anthracycline cardiotoxicity.
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic; D004205:Cromolyn Sodium / Q000494:pharmacology; D004317:Doxorubicin / Q000097:blood / Q000633:toxicity; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects*; D009279:Naphthacenes / Q000633:toxicity; D011817:Rabbits; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D004317:Doxorubicin; D004205:Cromolyn Sodium