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A Novel Ex Ovo Banding Technique to Alter Intracardiac Hemodynamics in an Embryonic Chicken System
Published on: May 13, 2016
Blood flow patterns underlie developmental heart defects
Madeline Midgett1, Kent Thornburg2, Sandra Rugonyi3,2
1Biomedical Engineering, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon; and.
Insights
Altered embryonic blood flow significantly impacts heart development, leading to specific congenital heart defects. This study reveals a dose-response relationship between blood flow changes and cardiac malformations, suggesting a key role for hemodynamics.
Area of Science:
- Developmental Biology
- Cardiovascular Physiology
- Embryology
Background:
- Congenital heart defects (CHDs) are often linked to genetic factors, but the role of embryonic hemodynamics is less understood.
- Early embryonic blood flow patterns are critical for normal cardiovascular development.
- The precise relationship between altered embryonic blood flow and specific cardiac malformations requires further investigation.
Purpose of the Study:
- To investigate the predictive value of anomalous embryonic blood flow patterns for cardiac defects.
- To quantify the relationship between altered blood flow dynamics and the development of specific cardiovascular malformations.
- To establish a dose-response correlation between hemodynamic stimuli and cardiac phenotypes in an embryonic model.
Main Methods:
- Utilized the chicken embryo model to experimentally alter embryonic blood flow.
- Quantified the effects of restricted cardiac inflow and graded outflow constriction on heart development.
- Observed and categorized resulting cardiac and vascular malformations, including ventricular septal defects and pharyngeal arch artery defects.
Main Results:
- Reduced cardiac inflow and graded outflow constriction led to reproducible cardiac abnormalities.
- Specific outflow constriction levels correlated with distinct defects: 10-35% constriction caused ventricular septal defects, while 35-60% caused double outlet right ventricle.
- Vitelline vein ligation resulted predominantly in pharyngeal arch artery malformations, demonstrating the impact of altered hemodynamics on vascular development.
Conclusions:
- Embryonic blood flow dynamics are a significant determinant of cardiac structure and function, influencing specific malformation types.
- Hemodynamic-associated cardiac defects in this model recapitulate those seen in human genetic disorders.
- Understanding embryonic blood flow is crucial for elucidating the root causes of congenital heart disease and developing future prevention and treatment strategies.
Abstract:
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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