Hemodynamic patterning of the avian atrioventricular valve

In this study, we develop an innovative approach to rigorously quantify the evolving hemodynamic environment of the atrioventricular (AV) canal of avian embryos. Ultrasound generated velocity profiles were imported into Micro‐Computed Tomography generated anatomically precise cardiac geometries between Hamburger‐Hamilton (HH) stages 17 and 30. Computational fluid dynamic simulations were then conducted and iterated until results mimicked in vivo observations. Blood flow in tubular hearts (HH17) was laminar with parallel streamlines, but strong vortices developed simultaneous with expansion of the cushions and septal walls. For all investigated stages, highest wall shear stresses (WSS) are localized to AV canal valve–forming regions. Peak WSS increased from 19.34 dynes/cm2 at HH17 to 287.18 dynes/cm2 at HH30, but spatiotemporally averaged WSS became 3.62 dynes/cm2 for HH17 to 9.11 dynes/cm2 for HH30. Hemodynamic changes often preceded and correlated with morphological changes. These results establish a quantitative baseline supporting future hemodynamic analyses and interpretations. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.

[1]  Gabriel Acevedo-Bolton,et al.  Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis , 2003, Nature.

[2]  Robert M. Nerem,et al.  Transcriptional Profiles of Valvular and Vascular Endothelial Cells Reveal Phenotypic Differences: Influence of Shear Stress , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[3]  David Sedmera,et al.  Pressure overload alters stress-strain properties of the developing chick heart. , 2003, American journal of physiology. Heart and circulatory physiology.

[4]  John W. Weidner,et al.  Mathematical Modeling of Flow-Generated Forces in an In Vitro System of Cardiac Valve Development , 2009, Annals of Biomedical Engineering.

[5]  J. McLachlan,et al.  Looping of chick embryo hearts in vitro. , 1990, Journal of anatomy.

[6]  C. Gaber Doppler echocardiography. , 1991, Problems in veterinary medicine.

[7]  Audrey C. Marshall,et al.  Balloon Dilation of Severe Aortic Stenosis in the Fetus: Potential for Prevention of Hypoplastic Left Heart Syndrome Candidate Selection, Technique, and Results of Successful Intervention , 2004, Circulation.

[8]  R. Nerem,et al.  Endothelial cell signaling and cytoskeletal changes in response to shear stress. , 1993, Frontiers of medical and biological engineering : the international journal of the Japan Society of Medical Electronics and Biological Engineering.

[9]  R. Price,et al.  Three‐dimensional model system of valvulogenesis , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[10]  Jerry Westerweel,et al.  In vivo micro particle image velocimetry measurements of blood-plasma in the embryonic avian heart. , 2006, Journal of biomechanics.

[11]  Clifford Matthews,et al.  Basic fluid mechanics , 2002 .

[12]  L. Miller,et al.  Flow within models of the vertebrate embryonic heart. , 2009, Journal of theoretical biology.

[13]  K. Yutzey,et al.  Heart Valve Development: Regulatory Networks in Development and Disease , 2009, Circulation research.

[14]  Michael Liebling,et al.  Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart , 2009, PLoS biology.

[15]  E. Clark,et al.  Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions , 1999, The Anatomical record.

[16]  Roger R Markwald,et al.  Transitions in Early Embryonic Atrioventricular Valvular Function Correspond With Changes in Cushion Biomechanics That Are Predictable by Tissue Composition , 2007, Circulation research.

[17]  E. Clark,et al.  Developmental Hemodynamic Changes in the Chick Embryo from Stage 18 to 27 , 1982, Circulation research.

[18]  R E Poelmann,et al.  Measurements of the wall shear stress distribution in the outflow tract of an embryonic chicken heart , 2010, Journal of The Royal Society Interface.

[19]  Robert E Guldberg,et al.  Quantitative volumetric analysis of cardiac morphogenesis assessed through micro‐computed tomography , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[20]  Jonathan T Butcher,et al.  An ex-ovo chicken embryo culture system suitable for imaging and microsurgery applications. , 2010, Journal of visualized experiments : JoVE.

[21]  L. Taber,et al.  Passive stress-strain measurements in the stage-16 and stage-18 embryonic chick heart. , 1997, Journal of biomechanical engineering.

[22]  R. Leask,et al.  The development of 3-D, in vitro, endothelial culture models for the study of coronary artery disease , 2009, Biomedical engineering online.

[23]  D. Sahn,et al.  Flow in the Early Embryonic Human Heart , 2003, Pediatric Cardiology.

[24]  Robert M Nerem,et al.  Valvular endothelial cells regulate the phenotype of interstitial cells in co-culture: effects of steady shear stress. , 2006, Tissue engineering.

[25]  L A Taber,et al.  Residual strain in the ventricle of the stage 16-24 chick embryo. , 1993, Circulation research.

[26]  T. Kohl,et al.  Fetal Echocardiography: New Grounds to Explore During Fetal Cardiac Intervention , 2002, Pediatric Cardiology.

[27]  B. M. Patten,et al.  Valvular action in the embryonic chick heart by localized apposition of endocardial masses , 1948, The Anatomical record.

[28]  J. Hurlé,et al.  Malformations of the semilunar valves produced in chick embryos by mechanical interference with cardiogenesis , 1983, Anatomy and Embryology.

[29]  R E Poelmann,et al.  Intracardiac blood flow patterns related to the yolk sac circulation of the chick embryo. , 1995, Circulation research.

[30]  D. Birchall,et al.  Analysis of haemodynamic disturbance in the atherosclerotic carotid artery using computational fluid dynamics , 2006, European Radiology.

[31]  Roger R Markwald,et al.  Valvulogenesis: the moving target , 2007, Philosophical Transactions of the Royal Society B: Biological Sciences.

[32]  S. Chien,et al.  Viscosity of turkey blood: rheology of nucleated erythrocytes. , 1970, Microvascular research.

[33]  David Sedmera,et al.  High‐frequency ultrasonographic imaging of avian cardiovascular development , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[34]  D. Christensen,et al.  Dependence of Aortic Arch Morphogenesis on Intracardiac Blood Flow in the Left Atrial Ligated Chick Embryo , 2009, Anatomical record.

[35]  Robert G. Gourdie,et al.  Hemodynamics Is a Key Epigenetic Factor in Development of the Cardiac Conduction System , 2003, Circulation research.

[36]  Kerem Pekkan,et al.  Aortic Arch Morphogenesis and Flow Modeling in the Chick Embryo , 2009, Annals of Biomedical Engineering.

[37]  M. Jenkins,et al.  In vivo gated 4D imaging of the embryonic heart using optical coherence tomography. , 2007, Journal of biomedical optics.

[38]  Sandra Rugonyi,et al.  Finite element modeling of blood flow-induced mechanical forces in the outflow tract of chick embryonic hearts , 2007 .

[39]  O. Jaffee Hemodynamic factors in the development of the chick embryo heart , 1965, The Anatomical record.

[40]  R. Markwald,et al.  Living Morphogenesis of the Heart , 1998, Cardiovascular Molecular Morphogenesis.

[41]  N. Hu,et al.  Hemodynamics of the Stage 12 to Stage 29 Chick Embryo , 1989, Circulation research.

[42]  Michael Liebling,et al.  Rapid three‐dimensional imaging and analysis of the beating embryonic heart reveals functional changes during development , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[43]  David C. Wilcox,et al.  Basic Fluid Mechanics , 1998 .

[44]  Orlando Aristizábal,et al.  Embryonic Heart Failure in NFATc1−/− Mice: Novel Mechanistic Insights From In Utero Ultrasound Biomicroscopy , 2004, Circulation research.

[45]  Girard Pr,et al.  Endothelial cell signaling and cytoskeletal changes in response to shear stress. , 1993 .

[46]  R. Arcilla,et al.  Intracardiac Flow Patterns in Early Embryonic Life: A Reexamination , 1983, Circulation research.

[47]  M. Dickinson,et al.  The Effects of Hemodynamic Force on Embryonic Development , 2010, Microcirculation.

[48]  J. Folkman,et al.  A simple procedure for the long-term cultivation of chicken embryos. , 1974, Developmental biology.

[49]  Z. RYCHTER,et al.  A Micromethod for Determination of the Circulating Blood Volume in Chick Embryos , 1955, Nature.

[50]  Anna I Hickerson,et al.  The Embryonic Vertebrate Heart Tube Is a Dynamic Suction Pump , 2006, Science.

[51]  J. Epstein,et al.  Rapid 3D Phenotyping of Cardiovascular Development in Mouse Embryos by Micro-CT With Iodine Staining , 2010, Circulation. Cardiovascular imaging.

[52]  Kim Van der Heiden,et al.  Fluid Shear Stress and Inner Curvature Remodeling of the Embryonic Heart. Choosing the Right Lane! , 2008, TheScientificWorldJournal.

[53]  M. Yacoub,et al.  Asymmetric redirection of flow through the heart , 2000, Nature.

[54]  Martin Baiker,et al.  Changes in Shear Stress–Related Gene Expression After Experimentally Altered Venous Return in the Chicken Embryo , 2005, Circulation research.