Blood Flow Disturbance and Morphological Alterations Following the Right Atrial Ligation in the Chick Embryo

Abstract

Collectively known as congenital heart defects (CHDs), cardiac abnormalities at birth are the most common forms of neonatal defects. Being principally responsible for the heart‘s pumping power, ventricles are particularly affected by developmental abnormalities, such as flow disturbances or genomic defects. Hypoplastic Right Heart Syndrome (HRHS) is a rare disease where the right ventricle is underdeveloped. In this study, we introduce a surgical procedure performed on chick embryo, termed right atrial ligation (RAL) for disturbing hemodynamics within the right heart aiming in order to generate an animal model of HRHS. RAL is a new surgical manipulation, similar to the well-studied left atrial ligation (LAL) surgery but it induces the hemodynamic change into the right side of the heart. After inducing RAL, We utilized techniques such as Doppler ultrasound, x-ray micro-CT, histology, and computational fluid dynamics (CFD) analysis, for a comprehensive functional and structural analysis of a developing heart. Our results displayed that RAL does not induce severe flow disturbance and ventricular abnormalities consistent with clinical findings. This study allows us to better understand the hemodynamics-driven CHD development and sensitivities of ventricles under disturbed flows.

Experimental assessment of cardiovascular physiology in the chick embryo

“…51,60 For example, recently, we demonstrated that surgical interference (left atrial ligation) affected hemodynamics and induced clinically relevant cardiac disease morphologies. 62 In a following study, we introduced a new surgical approach called right atrial ligation to study the influence of right-side flow disturbance in chick embryo heart development 15.…”

“…Thus, the chick embryo's heart and vasculature are visible and accessible for experimentation by removing a small piece of eggshell (Figure 1). Due to these attributes and the accessibility of chicken eggs, it is not surprising that the chick embryo has become established as a premier developmental animal model for studying cardiovascular physiology 14 and an excellent platform to explore the influences of hemodynamic forces within the cardiovascular system 15‐17 …”

“…Due to these attributes and the accessibility of chicken eggs, it is not surprising that the chick embryo has become established as a premier developmental animal model for studying cardiovascular physiology 14 and an excellent platform to explore the influences of hemodynamic forces within the cardiovascular system. [15][16][17] The chick embryo model is also helpful in studying new blood vessel formation (angiogenesis/vasculogenesis). 18 The intraembryonic and extraembryonic vitelline vessels branch across the yolk in a predictable pattern.…”

Quantitative OCT angiography toward 4D blood flow analysis in embryonic cardiovascular system

“…Investigating blood flow is therefore important to understanding heart development, but current capabilities in studying early mammalian blood flow patterns are limited. Aspects of biomechanical regulation of cardiac development have been studied in a number of species and by computational models [6,7]. Toward investigation of the biomechanical factors regulating cardiac development in mouse models of human diseases, recent research has established optical coherence tomography (OCT) imaging of mouse embryonic cardiodynamics [8][9][10][11][12].…”

Computational Modeling of Motile Cilia-Driven Cerebrospinal Flow in the Brain Ventricles of Zebrafish Embryo

“…For a deeper understanding of the cilia-driven flow, it is necessary to numerically model the problem and solve the physically governing fluid flow equations during the movement of the cilia. Computational fluid dynamics (CFD) is an important modality for investigating the biological flows in the human body which cannot be directly analyzed using experimental visualization techniques, such as in cilia-driven flow [ 62 , 63 ]. The complex flow geometries can be extracted with the use of image-processing techniques [ 64 ].…”