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      Fluid mechanics of the left atrial ligation chick embryonic model of hypoplastic left heart syndrome

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          Abstract

          Left atrial ligation (LAL) of the chick embryonic heart at HH21 is a model of the hypoplastic left heart syndrome (HLHS) disease, demonstrating morphological and hemodynamic features similar to human HLHS cases. Since it relies on mechanical intervention without genetic or pharmacological manipulations, it is a good model for understanding the biomechanics origins of such HLHS malformations. To date, however, the fluid mechanical environment of this model is poorly understood. In the current study, we performed 4D ultrasound imaging of LAL and normal chick embryonic hearts and 4D cardiac flow simulations to help shed light on the mechanical environment that may lead to the HLHS morphology. Results showed that the HH25 LAL atrial function was compromised, and velocities in the ventricle were reduced. The HH25 LAL ventricles developed a more triangular shape with a sharper apex, and in some cases, the atrioventricular junction shifted medially. These changes led to more sluggish flow near the ventricular free wall and apex, where more fluid particles moved in an oscillatory manner with the motion of the ventricular wall, while slowly being washed out, resulting in lower wall shear stresses and higher oscillatory indices. Consequent to these flow conditions, at HH28, even before septation is complete, the left ventricle was found to be hypoplastic while the right ventricle was found to be larger in compensation. Our results suggest that the low and oscillatory flow near the left side of the heart may play a role in causing the HLHS morphology in the LAL model.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s10237-021-01447-3.

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          Most cited references32

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          Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005.

          To determine an accurate estimate of the prevalence of congenital heart defects (CHD) using current standard diagnostic modalities. We obtained data on infants with CHD delivered during 1998 to 2005 identified by the Metropolitan Atlanta Congenital Defects Program, an active, population-based, birth defects surveillance system. Physiologic shunts in infancy and shunts associated with prematurity were excluded. Selected infant and maternal characteristics of the cases were compared with those of the overall birth cohort. From 1998 to 2005 there were 398 140 births, of which 3240 infants had CHD, for an overall prevalence of 81.4/10 000 births. The most common CHD were muscular ventricular septal defect, perimembranous ventricular septal defect, and secundum atrial septal defect, with prevalence of 27.5, 10.6, and 10.3/10 000 births, respectively. The prevalence of tetralogy of Fallot, the most common cyanotic CHD, was twice that of transposition of the great arteries (4.7 vs 2.3/10 000 births). Many common CHD were associated with older maternal age and multiple-gestation pregnancy; several were found to vary by sex. This study, using a standardized cardiac nomenclature and classification, provides current prevalence estimates of the various CHD subtypes. These estimates can be used to assess variations in prevalence across populations, time, or space.
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            The complex genetics of hypoplastic left heart syndrome

            Cecilia Lo and colleagues report the recovery of mice with hypoplastic left heart syndrome (HLHS) from a large mutagenesis screen. They find genetic heterogeneity among HLHS mice and functionally validate mutations in two genes, Sap130 and Pcdha, as contributing to HLHS in a combinatorial manner.
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              Pulsatile flow in the human left coronary artery bifurcation: average conditions.

              Xiaoyi He (1996)
              The localization of atherosclerosis in the coronary arteries may be governed by local hemodynamic features. In this study, the pulsatile hemodynamics of the left coronary artery bifurcation was numerically simulated using the spectral element method for realistic in vivo anatomic and physiologic conditions. The velocity profiles were found to be skewed in both the left anterior descending and the circumflex coronary arteries. Velocity skewing arose from the bifurcation as well as from the curvature of the artery over the myocardial surface. Arterial wall shear stress was significantly lower in the bifurcation region, including the side walls. The greatest oscillatory behavior was localized to the outer wall of the circumflex artery. The time-averaged mean wall shear stress varied from about 3 to 98 dynes/cm2 in the left coronary artery system. The highly localized distribution of low and oscillatory shear stress along the walls strongly correlates with the focal locations of atheroma in the human left coronary artery.
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                Author and article information

                Contributors
                c.yap@imperial.ac.uk
                Journal
                Biomech Model Mechanobiol
                Biomech Model Mechanobiol
                Biomechanics and Modeling in Mechanobiology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1617-7959
                1617-7940
                28 March 2021
                28 March 2021
                2021
                : 20
                : 4
                : 1337-1351
                Affiliations
                [1 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Department of Biomedical Engineering, , National University of Singapore, ; Singapore, Singapore
                [2 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Department of Bioengineering, , Imperial College London, ; London, UK
                Author information
                http://orcid.org/0000-0003-2918-3077
                Article
                1447
                10.1007/s10237-021-01447-3
                8298253
                33774755
                f134e777-e54d-44cc-8da9-2a7e6cc77a31
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 31 August 2020
                : 6 March 2021
                Funding
                Funded by: Singapore Ministry of Education
                Award ID: MOE2018-T2-1-003
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000761, Imperial College London;
                Award ID: Startup Funding
                Award Recipient :
                Categories
                Original Paper
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2021

                Biophysics
                embryonic heart biomechanics,hypoplastic left heart syndrome,fluid mechanics,chick embryonic left atrial ligation

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