Protective effect of ouabain on adriamycin-induced cardiovascular anomalies in chick embryos.
Adriamycin (2.5-10.0 micrograms) was administered to 4 1/2 and 5 day embryonic chicks (Hamburger-Hamilton developmental stages 24-26) to investigate the effect of the drug on cardiovascular morphogenesis. The drug produced dose-related increases in both mortality rate and malformation frequency with a maximum incidence of 82% cardiovascular anomalies following a dose of 10.0 micrograms/egg (P less than .001 relative to saline controls). Frequencies of embryos with ventricular septal defect (P less than .005), dextroposition of the aorta (P less than .005), or aortic arch anomalies (P less than .05) were significantly higher than among controls. In a second study, embryos were pretreated with ouabain (12.2 micrograms), verapamil (0.5 micrograms), coenzyme Q10 (100 micrograms, 200 micrograms), or vitamin E (1.0 mg, 5.0 mg)--agents previously shown to protect against adriamycin-induced cardiotoxicity. Pretreatment of embryos with ouabain significantly reduced the incidence of cardiovascular malformations induced by adriamycin from 55 to 21% (P less than .05). A major protective effect was observed relative to the induction of ventricular septal defect, the frequency of which was reduced from 45 to 14% (P less than .05). However, administration of verapamil, coenzyme Q10, or vitamin E did not have an appreciable effect on adriamycin-induced frequencies of cardiovascular malformations. Negative inotropism is suggested as a mechanism for adriamycin-induced cardiac anomalies but warrants further study.
Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison 53706.
Y
Y
Takagi
H J
HJ
Bruyere
T
T
Nishikawa
D000818:Animals; D002642:Chick Embryo; D003067:Coenzymes; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006321:Heart / Q000187:drug effects / Q000196:embryology; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000196:embryology; D009024:Morphogenesis / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D003067:Coenzymes; D014451:Ubiquinone; D014810:Vitamin E; D010042:Ouabain; D004317:Doxorubicin; D014700:Verapamil; C024989:coenzyme Q10