Ishikawa S, Gilbert E F, Bruyere H J, Cheung M O
Teratology. 1978 Aug;18(1):23-30. doi: 10.1002/tera.1420180106.
Theophylline(1 ml 0.02 M in 0.15 M saline) was administered to embryonic chicks (Hamburger-Hamilton developmental stages 24.27). The drug was topically applied to the surface of the chorioallantoic membrane in the vicinity of the embryonic heart. At necropsy, 63% (44/70) of the theophylline-exposed embryos demonstrated an aneurysm in the ascending aorta. Among the cases exhibiting aortic aneurysm, 48% (21/44) of the embryos demonstrated ventricular septal defects. Four cases of truncus arteriosus were also observed. The morphogenesis and mechanism of theophylline-induced cardiac defects with accompanying aortic aneurysm may be related to the development of the conotruncal region of the heart.