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American Journal of Pathology, Vol 112, 258-266, Copyright © 1983 by American Society for Investigative Pathology

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Light- and electron-microscopic observations of theophylline-induced aortic aneurysms in embryonic chicks

H Yokoyama, R Matsuoka, HJ Bruyere Jr, EF Gilbert and H Uno

These investigators have previously developed a model for inducing aortic aneurysms by administering theophylline or caffeine to embryonic chicks. This report describes light-microscopic and ultrastructural changes in aortic walls of theophylline-treated embryos relative to saline-treated controls. Light-microscopic examination of areas of permanent aortic dilatation revealed thinning of the medial layer due to a marked decrease in the number of medial cells. Electron- microscopic observation of aortic walls with aneurysms revealed widely scattered medial cells with scanty cytoplasm containing poorly developed microorganelles, a markedly widened intercellular space with dispersed elastic and collagen fibers in the tunica media, and a disruption of endothelial cells. It is suggested that the induction of aortic aneurysms by theophylline in chick embryos may be attributed to two factors: 1) atrophy and subsequent hypoplasia of the aortic media possibly resulting from an elevated intracellular cyclic adenosine 3',5'-monophosphate, which inhibits mitosis in medial cells, and 2) altered hemodynamics due to the action of theophylline on the embryonic heart.