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Extraembryonic venous obstructions lead to cardiovascular malformations and can be embryolethal
B Hogers1, M C DeRuiter, A C Gittenberger-de Groot
1Department of Anatomy and Embryology, Leiden University Medical Center, The Netherlands.
Insights
Altering placental blood flow in a chicken model caused cardiovascular malformations like ventricular septum defects. These heart defects occurred regardless of where blood flow was restricted, suggesting flow changes impact development.
Area of Science:
- Developmental biology
- Cardiovascular science
- Embryology
Background:
- Placental blood flow is crucial for fetal development.
- Understanding its impact on heart development is essential.
Purpose of the Study:
- To investigate how manipulating extraembryonic blood flow affects human heart development using an embryonic chicken model.
- To correlate intracardiac flow patterns with heart malformations.
Main Methods:
- Ligation of vitelline veins to alter blood flow.
- Visualization of blood flow using Indian ink.
- Morphological evaluation of hearts post-cardiac septation.
- Analysis of ligation position impact on malformation frequency and severity.
Main Results:
- Different ligation positions yielded distinct intracardiac flow patterns.
- Long-term ligation consistently led to cardiovascular malformations, including ventricular septum defects (VSDs), semilunar valve anomalies, and pharyngeal arch artery malformations.
- Mortality was significantly higher with left lateral vitelline vein ligation.
Conclusions:
- Early extraembryonic venous obstruction alters flow patterns and likely shear stress.
- This leads to a spectrum of cardiovascular malformations irrespective of ligation site.
- Delayed interventricular foramen closure may reduce VSD incidence in later stages.
Objective:
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.
Methods:
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.
Results:
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.
Conclusions:
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.