Abstract

The great arteries develop from symmetrical aortic arch arteries which are extensively remodeled. These events are vulnerable to perturbations. Hemodynamic forces have a significant role in this remodeling. In this study, optical coherence tomography (OCT) visualized live avian embryos for staging and measuring pharyngeal arch morphology. Measurements acquired with our orientation-independent, dual-angle Doppler OCT technique revealed that ethanol exposure leads to higher absolute blood flow, shear stress, and retrograde flow. Ethanol-exposed embryos had smaller cardiac neural crest (CNC) derived pharyngeal arch mesenchyme and fewer migrating CNC-derived cells. These differences in forces and CNC cell numbers could explain the abnormal aortic arch remodeling.

Highlights

  • A recent survey of 345,076 women aged 18-44 years in the United States found that 7.6% of pregnant women (555 out of 13,880) admitted to alcohol use and 1.4% (194 out of 13,880) admitted to binge drinking [1]

  • The results of this study suggested that the peak forward and reverse blood shear stress, rather than the average blood flow, may be a critical factor involved in the hemodynamic response to ethanol exposure

  • optical coherence tomography (OCT) images were used to acquire hemodynamic measurements including percentage of retrograde blood flow, average blood flow, average shear stress, oscillatory shear index, peak forward and peak retrograde shear stress. These measurements were possible due to a recently-developed orientationindependent, dual-angle Doppler OCT technique which enabled rapid measurement of absolute blood flow in a region where vessel orientation is challenging to determine due to large curvatures [32]

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Summary

Introduction

A recent survey of 345,076 women aged 18-44 years in the United States found that 7.6% of pregnant women (555 out of 13,880) admitted to alcohol use and 1.4% (194 out of 13,880) admitted to binge drinking [1]. Previous studies documented normal aortic arch development through the use of corrosion casts, fluorescent dyes, and micro-particle imaging velocimetry (μPIV) [13, 34,35,36] These investigators examined the structural remodeling of the vessels and measured the blood flow at various stages of development. We previously established and studied a quail model of FAS that mimics a binge-drinking exposure at the stage of gastrulation, at which point a woman may not yet be aware of her pregnancy [31, 33] This model was shown to result in abnormal development of the great arteries including defects such as double outlet right ventricle, misaligned aorta, and valve abnormalities that are similar to the cardiac defects observed in individuals with FAS [33]. We measured the volume of (largely neural crest derived) mesenchyme surrounding the aortic arch arteries to determine whether reduction in the precursors of the support cells of the vessels (e.g., vascular smooth muscle cells) might be limiting the growth of the great vessel dimensions

Embryo preparation
Optical coherence tomography imaging
Embryo staging
Hemodynamic measurements
Pharyngeal arch tissue measurement
Neural crest cell immuno-labeling
Results
Discussion
Full Text
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