Objective: To expand our knowledge concerning the effect of placental blood
flow on human heart development, we used an embryonic chicken model in whi
ch extraembryonic blood flow was manipulated. Methods: First, one of the th
ree major vitelline veins was ligated, while blood flow was visualized with
Indian ink. In this way, we could study the effect of different ligation p
ositions on intracardiac flow patterns. Secondly, these vitelline veins wer
e ligated permanently with a microclip until cardiac septation was complete
d, thereafter, the hearts were morphologically evaluated. In this way, we c
ould study the impact of the ligation position on the severity and frequenc
y of heart malformations. On combining the results, we were able to study t
he effect of different intracardiac flow patterns on heart development. Res
ults: Although ligation of each vein resulted in different intracardiac flo
w patterns, long-term ligation resulted in similar cardiovascular malformat
ions in survivors. These consisted mainly of ventricular septum defects (VS
Ds), semilunar valve anomalies, and pharyngeal arch artery malformations. T
here was no significant difference (p>0.05) between the ligation position a
nd the incidence of cardiovascular malformations. However, the percentage m
ortality after clipping the left lateral vitelline vein was significantly h
igher (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. I
n postseptation stages, these result in a spectrum of cardiovascular malfor
mations irrespective of the ligation position. A diminished incidence of VS
Ds in the oldest stage was attributed to delayed closure of the interventri
cular foramen. (C) 1999 Elsevier Science B.V. All rights reserved.