Extraembryonic venous obstructions lead to cardiovascular malformations and can be embryolethal

To expand our knowledge concerning the effect of placental blood flow on human heart development, we used an embryonic chicken model in which extraembryonic blood flow was manipulated. First, one of the three major vitelline veins was ligated, while blood flow was visualized with Indian ink. In this way, we could study the effect of different ligation positions on intracardiac flow patterns. Secondly, these vitelline veins were ligated permanently with a microclip until cardiac septation was completed, thereafter, the hearts were morphologically evaluated. In this way, we could study the impact of the ligation position on the severity and frequency of heart malformations. On combining the results, we were able to study the effect of different intracardiac flow patterns on heart development. Although ligation of each vein resulted in different intracardiac flow patterns, long-term ligation resulted in similar cardiovascular malformations in survivors. These consisted mainly of ventricular septum defects (VSDs), semilunar valve anomalies, and pharyngeal arch artery malformations. There was no significant difference (p > 0.05) between the ligation position and the incidence of cardiovascular malformations. However, the percentage mortality after clipping the left lateral vitelline vein was significantly higher (p < 0.05) than after ligation of either the right lateral or posterior vitelline vein. Early extraembryonic venous obstruction leads to altered flow patterns, which probably result in shear stress changes. In postseptation stages, these result in a spectrum of cardiovascular malformations irrespective of the ligation position. A diminished incidence of VSDs in the oldest stage was attributed to delayed closure of the interventricular foramen.