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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Heart+Circ+Physiol
2017 ; 312
(3
): H632-H642
Nephropedia Template TP
Am J Physiol Heart Circ Physiol
2017[Mar]; 312
(3
): H632-H642
PMID28062416
show ga
Although cardiac malformations at birth are typically associated with genetic
anomalies, blood flow dynamics also play a crucial role in heart formation.
However, the relationship between blood flow patterns in the early embryo and
later cardiovascular malformation has not been determined. We used the chicken
embryo model to quantify the extent to which anomalous blood flow patterns
predict cardiac defects that resemble those in humans and found that restricting
either the inflow to the heart or the outflow led to reproducible abnormalities
with a dose-response type relationship between blood flow stimuli and the
expression of cardiac phenotypes. Constricting the outflow tract by 10-35% led
predominantly to ventricular septal defects, whereas constricting by 35-60% most
often led to double outlet right ventricle. Ligation of the vitelline vein caused
mostly pharyngeal arch artery malformations. We show that both cardiac inflow
reduction and graded outflow constriction strongly influence the development of
specific and persistent abnormal cardiac structure and function. Moreover, the
hemodynamic-associated cardiac defects recapitulate those caused by genetic
disorders. Thus our data demonstrate the importance of investigating embryonic
blood flow conditions to understand the root causes of congenital heart disease
as a prerequisite to future prevention and treatment.NEW & NOTEWORTHY Congenital
heart defects result from genetic anomalies, teratogen exposure, and altered
blood flow during embryonic development. We show here a novel "dose-response"
type relationship between the level of blood flow alteration and manifestation of
specific cardiac phenotypes. We speculate that abnormal blood flow may frequently
underlie congenital heart defects.
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