In vitro hemodynamic investigation of the embryonic aortic arch at late gestation
Introduction
The fetal aortic arch is formed by the great vessels of the human arterial circulation and functions as a conduit for multiple flow streams during fetal life. The fetal aortic arch has two inlets represented by the right and left ventricular outflow tracks (RVOT and LVOT), and distributes oxygenated blood from the placenta and deoxygenated blood from the fetus via two outlets represented by the ascending aorta and pulmonary arteries to the head-neck vessels and the descending aorta (DAo) (Brezinka, 2001; Long, 1990; Sadler, 2006). The fetal aortic arch is in constant transformation in order to optimally match the hemodynamic requirements of the growing embryo (Keller et al., 2007). The higher oxygen saturated blood from the placenta is diluted with deoxygenated blood through a series of mixing events, while maintaining preferential flow of higher saturated blood to the developing brain (Blackburn, 2006; Stock and Vacanti, 2001; Szwast and Rychik, 2005). The fetal circulation (Allan et al., 2000; Huhta, 2001; Kiserud, 2005; Phoon, 2001) functions in a fail-safe mode where brain perfusion is “spared” in the setting of reduced antegrade aortic arch flow due to the presence of a parallel circulation with the capacity for retrograde perfusion via the ductus arteriosus (DA) (Fig. 1a). While the DA usually involutes spontaneously during the first week of life, a persistent DA is a common post-natal cardiovascular problem and may be essential for survival in the setting of some forms of congenital heart disease (CHD) (Frydrychowicz et al., 2007; Schneider and Moore, 2006). Patency of the DA can be maintained pharmacologically to support systemic and/or pulmonary blood flow in the setting of complex, cyanotic CHD where hypoplasia of the LVOT reduces antegrade aortic arch flow or hypoplasia of the RVOT reduces antegrade PA flow.
Cardiovascular solid mechanics and hemodynamic studies of cardiac development have predominantly focused on early embryonic stages and ventricular flows (Gleason et al., 2004; Nerurkar et al., 2006; Ramasubramanian et al., 2006). In 1928, Harvard University anatomist Bremer sketched the 3D spiral flow streams in fetal chick hearts at several developmental stages and highlighted the association between form and flow (Bremer, 1928). Systematic in vivo flow visualization confirmed these observations where CHDs reproducibly created via altered venous flow patterns (Hogers et al., 1995). Engineering fluid dynamic analysis tools have only recently supported the quantification of these observations. Pioneering fluid mechanics experiments performed by Gharib and co-workers (Forouhar et al., 2006; Hove et al., 2003) used high-frame rate confocal particle image velocimetry systems on zebrafish embryos and by Vennemann et al. (2006) used conventional microscopic particle image velocimetry techniques in chick embryos. Limited data is available using complementary computational fluid dynamics (CFD) analysis in the developing human heart. DeGroff et al. (2003) used postmortem micro-dissected human fetal ventricles at the pre- and post-looping stages (Pentecost et al., 2001) and Loots et al. (2003) used a simplified tubular heart model to perform CFD simulations. More recently, analysis of fluid-structure interactions in the outflow-tract (Rugonyi et al., 2007), active embryonic heart analytical models (Taber et al., 2007), and mechanical loading of the atrioventricular cardiac cushions (Butcher et al., 2007) in chick embryo have been presented. To our knowledge the hemodynamics of fetal aortic arch during mid-to-late gestation period has not been investigated in spite of its clear significance to perinatal/neonatal arch structure and function (Friedman and Fahey, 1993; Maeno et al., 1999) and the clinical management of patients with CHD (Cohen, 2001; Hoffman and Kaplan, 2002). Likewise, excellent previous studies have investigated the dynamics of the embryonic circulation through lumped parameter models (Pennati et al., 2003; Pennati and Fumero, 2000; Peskin, 1981; Yoshigi and Keller, 1997; Yoshigi et al., 2000); the main focus of the current study is to identify the large scale 3D flow structures and baseline governing flow physics using experimental flow visualization and CFD models for the normal fetal aortic arch and for great vessel flow patterns in the setting of selected major CHDs.
Hemodynamics of the normal adult-scale aorta is a classical topic of cardiovascular fluid dynamics (Caro et al., 1978; Fung, 1984; McDonald, 1974) and has been extensively studied (Jin et al., 2003; Leuprecht et al., 2003; Mori and Yamaguchi, 2002; Morris et al., 2005; Nakamura et al., 2006; Shahcheraghi et al., 2002; Suo, 2005; Wood et al., 2001). A detailed literature survey is provided in our recent work, where an in vitro/in vivo validated, second-order accurate, transient CFD model of the neonatal aortic arch is developed (Pekkan et al., 2007a). Recent CFD models, focusing the normal mouse aortic-arch, revealed lower peak Reynolds and Womersley numbers (∼250 and ∼2) with significantly higher wall shear stress (Feintuch et al., 2007; Jin et al., 2007) compared to the human aorta, where low and oscillatory wall shear stress correlated with spatial protein expressions (Jin et al., 2007). Similarly, hemodynamics of the central PA tree has usually been studied in isolation (Hunter et al., 2006). Interestingly, the fetal aortic arch requires the integration of both of these arterial systems (pulmonary and systemic vascular beds driven by left and right hearts) in a single anatomical CFD domain due to its more complex parallel arrangement and challenging topology.
Section snippets
Idealized anatomical model
A geometric model of the human fetal aortic arch representing the late gestation period (24–34 weeks) was created using computer-aided design software (Proengineer) (Fig. 1a). Anatomical dimensions and orientations were selected based on literature (Achiron et al., 2000; Long, 1990; Mielke and Benda, 2000b) and confirmed through interviews with three experienced pediatric cardiologists. The parametric nature enabled practical implementation of several suggested anatomical corrections.
Based on
Pulmonary artery flow
Flow during the acceleration phase is found to be unidirectional with little swirl. During the deceleration phase, both flow visualization experiments and CFD results demonstrated distinct swirling flow at the PAs, Fig. 3 and supplemental Movie 1. Steady mean flow conditions also featured distinct swirling flow within the PAs. In the steady flow particle tracking experiments, a flow separation line extending to the RPA is observed along the RVOT due to the curvature of the main PA (supplemental
Discussion and conclusions
Recent advances in high-resolution ultrasound (Bonnet et al., 1999; Brackley et al., 2000; Cohen, 2001; Denkhaus and Winsberg, 1979; Hamar et al., 2006; Hecher et al., 1995; Tworetzky et al., 2001) and fetal cardiac MRI (Coakley, 2001; Fogel, 2006; Fogel et al., 2005; Hubbard and Harty, 1999; Liu et al., 2001) have demonstrated that aortic arch hemodynamics (Lenz and Chaoui, 2006) and great vessel anatomy (Axt-Fliedner et al., 2006; Hubbard and Harty, 1999) correlate with the prognosis of
Conflict of interest
Authors have no conflict of interest in our manuscript titled “In vitro hemodynamic investigation of the human embryonic aortic arch”.
Acknowledgments
This work is supported by an American Heart Association beginning-grant-in-aid, 0765284U and NIH BRP Grant HL67622. Mr. Nourparvar and Mr. Yerneni are supported through PURA (President's Undergraduate Research Awards). We also acknowledge the contributions of Drs. Shiva Sharma and W. James Parks in parametric CHD model development. Flow visualization is performed at Georgia Institute of Technology.
References (97)
- et al.
Outcome after prenatal diagnosis of hypoplastic left-heart syndrome: a case series
Lancet
(2000) Fetal diagnosis and management of congenital heart disease
Clinical Perinatology
(2001)- et al.
Hemodynamic changes in the fetal arteries during the second half of pregnancy assessed by Doppler velocimetry
European Journal of Obstetrics and Gynecology Reproductive Biology
(2007) Keeping abreast of advances in fetal cardiology
Early Human Development
(2006)- et al.
Effects of pulmonary afterload on the hemodynamics after the hemi-Fontan procedure
Medical Engineering & Physics
(2001) - et al.
The incidence of congenital heart disease
Journal of American College of Cardiology
(2002) - et al.
Prenatal magnetic resonance imaging of fetal anomalies
Seminars in Roentgenology
(1999) - et al.
Morphologic study of the ascending aorta and aortic arch in hypoplastic left hearts: Surgical implications
The Journal of Thoracic and Cardiovascular Surgery
(2007) Physiology of the fetal circulation
Seminar of Fetal Neonatal Medicine
(2005)- et al.
Multiscale modeling of the cardiovascular system: application to the study of pulmonary and coronary perfusions in the univentricular circulation
Journal of Biomechanics
(2005)
Multiscale modelling in biofluidynamics: application to reconstructive paediatric cardiac surgery
Journal of Biomechanics
Umbilical flow distribution to the liver and the ductus venosus in human fetuses during gestation: an anatomy-based mathematical modeling
Medical Engineering and Physics
Graphical and stereolithographic models of the developing human heart lumen
Computation of Medical Imaging Graph
Numerical modeling of simulated blood flow in idealized composite arterial coronary grafts: steady state simulations
Journal of Biomechanics
Hypoplastic left heart syndrome: from in-utero diagnosis to school age
Seminars on Fetal Neonatal Medicine
Current concepts in fetal cardiovascular disease
Clinical Perinatology
Accuracy of prenatal echocardiographic diagnosis and prognosis of fetuses with conotruncal anomalies
Journal of American College of Cardiology
Fetal pulmonary valvuloplasty for critical pulmonary stenosis or atresia with intact septum
Lancet
In vivo micro particle image velocity of blood-plasma in the embryonic avian heart
Journal of Biomechanics
The role of mechanical forces in dextral rotation during cardiac looping in the chick embryo
Development in Biology
Lumped parameter estimation for the embryonic chick vascular system: a time-domain approach using MLAB
Computer Methods and Programs in Biomedicine
Repair of coarctation of the aorta in neonates and infants: a thirty-year experience
Annals of Thoracic Surgery
Fetal aortic arch measurements between 14 and 38 weeks’ gestation: in-utero ultrasonographic study
Ultrasound in Obstetrics and Gynecology
Textbook of Fetal Cardiology
Development of hypoplastic left heart syndrome after diagnosis of aortic stenosis in the first trimester by early echocardiography
Ultrasound in Obstetrics and Gynecology
Placental, fetal, and transitional circulation revisited
Journal of Perinatal and Neonatal Nursing
Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality
Circulation
An interpretation of heart development
Journal of Anatomy
Fetal hemodynamics
Journal of Perinatal Medicine
Transitions in early embryonic atrioventricular valvular function correspond with changes in cushion biomechanics that are predictable by tissue composition
Circulation Research
The Mechanics of the Circulation
Experimental visualization of Lagrangian coherent structures in aperiodic flows
Physics of Fluids
Role of magnetic resonance imaging in fetal surgery
Topics in Magnetic Resonance Imaging
Flow in the early embryonic human heart: a numerical study
Pediatric Cardiology
Ultrasonic measurement of the fetal ventricular system
Radiology
Computer-assisted navigation applied to fetal cardiac intervention
International Journal in Medical Robotics
Hemodynamics in the mouse aortic arch as assessed by MRI, ultrasound, and numerical modeling
American Journal of Physiology—Heart and Circulatory Physiology
Cardiac magnetic resonance of single ventricles
Journal of Cardiovascular Magnetic Resonance
Preliminary investigations into a new method of functional assessment of the fetal heart using a novel application of ‘real-time’ cardiac magnetic resonance imaging
Fetal Diagnosis and Therapy
The embryonic vertebrate heart tube is a dynamic suction pump
Science
The transition from fetal to neonatal circulation: normal responses and implications for infants with heart disease
Seminars in Perinatology
Visualization of vascular hemodynamics in a case of a large patent ductus arteriosus using flow sensitive 3D CMR at 3 T
Journal of Cardiovascular Magnetic Resonance
Biodynamics: Circulation
A 2-D model of flow-induced alterations in the geometry, structure, and properties of carotid arteries
Journal of Biomechanical Engineering
Trends in fetal echocardiography and implications for clinical practice: 1985–2003
Journal of Ultrasound in Medicine
Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation. Arterial, intracardiac, and venous blood flow velocity studies
Circulation
Intracardiac blood flow patterns related to the yolk sac circulation of the chick embryo
Circulation Research
Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis
Nature
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