ETIOLOGY AND DEVELOPMENT OF CONGENITAL HEART DISEASE

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Strains of dogs with hereditary lesion-specific defects in cardiovascular development are used to study the pathogenesis of conotruncal septum defects (including tetralogy of fallot, ventricular septal defect, and persistent truncus arteriosus), pulmonary valve dysplasia, and patent ductus arteriosus. Comparing embryos from affected strains with normal control embryos at comparable stages of development, the investigations progress through classical embryologic studies of the time course of abnormalities in the shape and form of the developing heart, to investigation of the roles of cell proliferation, differential cell death, and formation of intercellular matrix in the genesis of these malformations. Methods used include wax plate reconstruction of the developing heart from serial sections, transmission electron microscopy, scanning electron microscopy of microdissected hearts, and Quantimet analysis of the relative volumes of cell vs extracellular matrix in sections from selected areas of the developing heart. Quantitative morphometric studies of mitotic activity and cell death utilize cytologic techniques. Autoradiography is used to assess cell replication (incorporation of tritiated thymidine into DNA) in sections from selected areas.