Development of the outflow tract and closure of the interventricular septum in the normal human heart

The majority of congenital heart malformations in humans involve defects in the atrioventricular valves, the crest of the interventricular septum, and/or the outflow tract, but the position and timing of these structures during cardiac development is controversial. We examined all 622 staged, serially sectioned normal human embryos and fetuses in the Carnegie Embryological Collection, and obtained a statistical tabulation of the appearance of the endocardial cushion components and surrounding structures for 382 embryos in good condition between stages 9 and 23 inclusive, when the heart normally develops. Accurately scaled drawings of ventral and lateral views of the hearts of 7 embryos from stage 13 through 22 were prepared from graphic reconstructions in order to visualize the relationships of the structures under consideration. We found that development of the outflow tract septum follows the apparent functional separation of both the left and right ventricles and the blood streams leaving them. Elevations of the endocardial cushion material are continuous throughout the outflow tract and develop as a consequence of the elliptical configuration imposed on the circular cross section of the outflow tract. The membranous interventricular septum is formed of cushion material in the space bounded by the outflow tract septum, interventricular septum, and the fused AV cushion and right outflow tract cushion. The results of this study are consistent with the assertion that functional separation of the aortic and pulmonary outflow tracts precedes anatomic septation, and that anatomic septation is brought about by mechanical modeling of developing myocardium and endocardial cushion material.