In vitro hemodynamic investigation of the embryonic aortic arch at late gestation

https://doi.org/10.1016/j.jbiomech.2008.03.013Get rights and content

Abstract

This study focuses on the dynamic flow through the fetal aortic arch driven by the concurrent action of right and left ventricles. We created a parametric pulsatile computational fluid dynamics (CFD) model of the fetal aortic junction with physiologic vessel geometries. To gain a better biophysical understanding, an in vitro experimental fetal flow loop for flow visualization was constructed for identical CFD conditions. CFD and in vitro experimental results were comparable. Swirling flow during the acceleration phase of the cardiac cycle and unidirectional flow following mid-deceleration phase were observed in pulmonary arteries (PA), head-neck vessels, and descending aorta. Right-to-left (oxygenated) blood flowed through the ductus arteriosus (DA) posterior relative to the antegrade left ventricular outflow tract (LVOT) stream and resembled jet flow. LVOT and right ventricular outflow tract flow mixing had not completed until ∼3.5 descending aorta diameters downstream of the DA insertion into the aortic arch. Normal arch model flow patterns were then compared to flow patterns of four common congenital heart malformations that include aortic arch anomalies. Weak oscillatory reversing flow through the DA junction was observed only for the Tetralogy of Fallot configuration. PA and hypoplastic left heart syndrome configurations demonstrated complex, abnormal flow patterns in the PAs and head-neck vessels. Aortic coarctation resulted in large-scale recirculating flow in the aortic arch proximal to the DA. Intravascular flow patterns spatially correlated with abnormal vascular structures consistent with the paradigm that abnormal intravascular flow patterns associated with congenital heart disease influence vascular growth and function.

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)

  • F. Migliavacca et al.

    Multiscale modelling in biofluidynamics: application to reconstructive paediatric cardiac surgery

    Journal of Biomechanics

    (2006)
  • G. Pennati et al.

    Umbilical flow distribution to the liver and the ductus venosus in human fetuses during gestation: an anatomy-based mathematical modeling

    Medical Engineering and Physics

    (2003)
  • J.O. Pentecost et al.

    Graphical and stereolithographic models of the developing human heart lumen

    Computation of Medical Imaging Graph

    (2001)
  • A.K. Politis et al.

    Numerical modeling of simulated blood flow in idealized composite arterial coronary grafts: steady state simulations

    Journal of Biomechanics

    (2007)
  • J. Rychik

    Hypoplastic left heart syndrome: from in-utero diagnosis to school age

    Seminars on Fetal Neonatal Medicine

    (2005)
  • A. Szwast et al.

    Current concepts in fetal cardiovascular disease

    Clinical Perinatology

    (2005)
  • A.J. Tometzki et al.

    Accuracy of prenatal echocardiographic diagnosis and prognosis of fetuses with conotruncal anomalies

    Journal of American College of Cardiology

    (1999)
  • G. Tulzer et al.

    Fetal pulmonary valvuloplasty for critical pulmonary stenosis or atresia with intact septum

    Lancet

    (2002)
  • P. Vennemann et al.

    In vivo micro particle image velocity of blood-plasma in the embryonic avian heart

    Journal of Biomechanics

    (2006)
  • D.A. Voronov et al.

    The role of mechanical forces in dextral rotation during cardiac looping in the chick embryo

    Development in Biology

    (2004)
  • M. Yoshigi et al.

    Lumped parameter estimation for the embryonic chick vascular system: a time-domain approach using MLAB

    Computer Methods and Programs in Biomedicine

    (2000)
  • K.J. Zehr et al.

    Repair of coarctation of the aorta in neonates and infants: a thirty-year experience

    Annals of Thoracic Surgery

    (1995)
  • R. Achiron et al.

    Fetal aortic arch measurements between 14 and 38 weeks’ gestation: in-utero ultrasonographic study

    Ultrasound in Obstetrics and Gynecology

    (2000)
  • L. Allan et al.

    Textbook of Fetal Cardiology

    (2000)
  • R. Axt-Fliedner et al.

    Development of hypoplastic left heart syndrome after diagnosis of aortic stenosis in the first trimester by early echocardiography

    Ultrasound in Obstetrics and Gynecology

    (2006)
  • S. Blackburn

    Placental, fetal, and transitional circulation revisited

    Journal of Perinatal and Neonatal Nursing

    (2006)
  • D. Bonnet et al.

    Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality

    Circulation

    (1999)
  • J.L. Bremer

    An interpretation of heart development

    Journal of Anatomy

    (1928)
  • C. Brezinka

    Fetal hemodynamics

    Journal of Perinatal Medicine

    (2001)
  • J.T. Butcher et al.

    Transitions in early embryonic atrioventricular valvular function correspond with changes in cushion biomechanics that are predictable by tissue composition

    Circulation Research

    (2007)
  • C.G. Caro et al.

    The Mechanics of the Circulation

    (1978)
  • A. Chrisohoides et al.

    Experimental visualization of Lagrangian coherent structures in aperiodic flows

    Physics of Fluids

    (2003)
  • F.V. Coakley

    Role of magnetic resonance imaging in fetal surgery

    Topics in Magnetic Resonance Imaging

    (2001)
  • C.G. DeGroff et al.

    Flow in the early embryonic human heart: a numerical study

    Pediatric Cardiology

    (2003)
  • H. Denkhaus et al.

    Ultrasonic measurement of the fetal ventricular system

    Radiology

    (1979)
  • S.P. Emery et al.

    Computer-assisted navigation applied to fetal cardiac intervention

    International Journal in Medical Robotics

    (2007)
  • A. Feintuch et al.

    Hemodynamics in the mouse aortic arch as assessed by MRI, ultrasound, and numerical modeling

    American Journal of Physiology—Heart and Circulatory Physiology

    (2007)
  • M.A. Fogel

    Cardiac magnetic resonance of single ventricles

    Journal of Cardiovascular Magnetic Resonance

    (2006)
  • M.A. Fogel et al.

    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

    (2005)
  • A.S. Forouhar et al.

    The embryonic vertebrate heart tube is a dynamic suction pump

    Science

    (2006)
  • A.H. Friedman et al.

    The transition from fetal to neonatal circulation: normal responses and implications for infants with heart disease

    Seminars in Perinatology

    (1993)
  • A. Frydrychowicz et al.

    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

    (2007)
  • Y.C. Fung

    Biodynamics: Circulation

    (1984)
  • R.L. Gleason et al.

    A 2-D model of flow-induced alterations in the geometry, structure, and properties of carotid arteries

    Journal of Biomechanical Engineering

    (2004)
  • B.D. Hamar et al.

    Trends in fetal echocardiography and implications for clinical practice: 1985–2003

    Journal of Ultrasound in Medicine

    (2006)
  • K. Hecher et al.

    Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation. Arterial, intracardiac, and venous blood flow velocity studies

    Circulation

    (1995)
  • B. Hogers et al.

    Intracardiac blood flow patterns related to the yolk sac circulation of the chick embryo

    Circulation Research

    (1995)
  • J.R. Hove et al.

    Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis

    Nature

    (2003)
  • Cited by (20)

    • Role of Computational Modelling in Planning and Executing Interventional Procedures for Congenital Heart Disease

      2017, Canadian Journal of Cardiology
      Citation Excerpt :

      Additionally, in some patients recurrent obstruction occurs, and either repeat surgical intervention or transcatheter intervention with angioplasty with or without stent placement is required.55 Computational modelling and CFD have been applied to study hemodynamics in the aortic arch of patients ranging from fetal life to elderly patients.56,57 There is a growing body of work that increased wall shear stress leads to worse vascular health,58 and CMR imaging with CFD analysis has been applied in surgically repaired aortic arches, with marked differences in wall shear stress on the basis of the underlying anatomy and surgical approach.59,60

    • Tunable Blood Shunt for Neonates With Complex Congenital Heart Defects

      2022, Frontiers in Bioengineering and Biotechnology
    View all citing articles on Scopus
    View full text