Skip to main content
SpringerLink
Log in

Growth and hemodynamics after early embryonic aortic arch occlusion

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

The majority of severe clinically significant forms of congenital heart disease (CHD) are associated with great artery lesions, including hypoplastic, double, right or interrupted aortic arch morphologies. While fetal and neonatal interventions are advancing, their potential ability to restore cardiac function, optimal timing, location, and intensity required for intervention remain largely unknown. Here, we combine computational fluid dynamics (CFD) simulations with in vivo experiments to test how individual pharyngeal arch artery hemodynamics alter as a result of local interventions obstructing individual arch artery flow. Simulated isolated occlusions within each pharyngeal arch artery were created with image-derived three-dimensional (3D) reconstructions of normal chick pharyngeal arch anatomy at Hamburger–Hamilton (HH) developmental stages HH18 and HH24. Acute flow redistributions were then computed using in vivo measured subject-specific aortic sinus inflow velocity profiles. A kinematic vascular growth-rendering algorithm was then developed and implemented to test the role of changing local wall shear stress patterns in downstream 3D morphogenesis of arch arteries. CFD simulations predicted that altered pressure gradients and flow redistributions were most sensitive to occlusion of the IVth arches. To evaluate these simulations experimentally, a novel in vivo experimental model of pharyngeal arch occlusion was developed and implemented using two-photon microscopy-guided femtosecond laser-based photodisruption surgery. The right IVth arch was occluded at HH18, and resulting diameter changes were followed for up to 24 h. Pharyngeal arch diameter responses to acute hemodynamic changes were predicted qualitatively but poorly quantitatively. Chronic growth and adaptation to hemodynamic changes, however, were predicted in a subset of arches. Our findings suggest that this complex biodynamic process is governed through more complex forms of mechanobiological vascular growth rules. Other factors in addition to wall shear stress or more complex WSS rules are likely important in the long-term arterial growth and patterning. Combination in silico/experimental platforms are essential for accelerating our understanding and prediction of consequences from embryonic/fetal cardiovascular occlusions and lay the foundation for noninvasive methods to guide CHD diagnosis and fetal intervention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Anderson DA, Tannehill JC, Pletcher RH (1984) Computational fluid mechanics and heat transfer. Hemisphere Publishing Corporation, New York

    MATH  Google Scholar 

  • Bajolle F, Zaffran S, Kelly RG, Hadchouel J, Bonnet D, Brown NA, Buckingham ME (2006) Rotation of the myocardial wall of the outflow tract is implicated in the normal positioning of the great arteries. Circ Res 98:421–428

    Article  Google Scholar 

  • Bayer IM, Adamson SL, Langille BL (1999) Atrophic remodeling of the artery-cuffed artery. Arterioscler Thromb Vasc Biol 19:1499–1505

    Article  Google Scholar 

  • Bergwerff M et al (1996) Onset of elastogenesis and downregulation of smooth muscle actin as distinguishing phenomena in artery differentiation in the chick embryo. Anat Embryol 194(6):545–557

    Article  Google Scholar 

  • Bharadwaj KN, Spitz C, Shekhar A, Yalcin HC, Butcher JT (2012) Computational fluid dynamics of developing avian outflow tract heart valves. Ann Biomed Eng 40:2212–2227

    Article  Google Scholar 

  • Bockman DE, Redmond ME, Kirby ML (1989) Alteration of early vascular development after ablation of cranial neural crest. Anat Rec 225(3):209–217. doi:10.1002/ar.1092250306

  • Bremer JL (1928) Experiments on the aortic arches in the chick. Anat Rec (Hoboken) 37:225–254

    Article  Google Scholar 

  • Broekhuizen ML, Mast F, Struijk PC, van der Bie W, Mulder PG, Gittenberger-de Groot AC, Wladimiroff JW (1993) Hemodynamic parameters of stage 20 to stage 35 chick embryo. Pediatr Res 34:44–46

    Article  Google Scholar 

  • Butcher JT, Sedmera D, Guldberg RE, Markwald RR (2007) Quantitative volumetric analysis of cardiac morphogenesis assessed through micro-computed tomography. Dev Dyn 236:802–809

    Article  Google Scholar 

  • Clark EB, Hu N, Frommelt P, Vandekieft GK, Dummett JL, Tomanek RJ (1989) Effect of increased pressure on ventricular growth in stage 21 chick embryos. Am J Physiol 257:H55–H61

    Google Scholar 

  • Culver JC, Dickinson ME (2010) The effects of hemodynamic force on embryonic development. Microcirculation 17:164–178

    Article  Google Scholar 

  • Davis JC (1986) Statistics and data analysis in geology, 2nd edn. John Wiley, New York

    Google Scholar 

  • deAlmeida A, McQuinn T, Sedmera D (2007) Increased ventricular preload is compensated by myocyte proliferation in normal and hypoplastic fetal chick left ventricle. Circ Res 100:1363–1370

    Article  Google Scholar 

  • Dor X, Corone P (1985) Migration and torsions of the conotruncus in the chick embryo heart: observational evidence and conclusions drawn from experimental intervention. Heart Vessels 1:195–211

    Article  Google Scholar 

  • Elzenga NJ, Gittenberger-de Groot AC (1985) Coarctation and related aortic arch anomalies in hypoplastic left heart syndrome. Int J Cardiol 8:379–393

  • Emery SP, Kreutzer J, Sherman FR, Fujimoto KL, Jaramaz B, Nikou C, Tobita K, Keller BB (2007) Computer-assisted navigation applied to fetal cardiac intervention. Int J Med Robot 3:187–198

    Article  Google Scholar 

  • Figueroa CA, Baek S, Taylor CA, Humphrey JD (2009) A computational framework for fluid-solid-growth modeling in cardiovascular simulations. Comput Methods Appl Mech Eng 198:3583–3602

    Article  MATH  MathSciNet  Google Scholar 

  • Gessner IH (1966a) Spectrum of congenital cardiac anomalies produced in chick embryos by mechanical interference with cardiogenesis. Circ Res 18:625–633

    Article  Google Scholar 

  • Gessner IH (1966b) Spectrum of congenital cardiac anomalies produced in chick embryos by mechanical interference with cardiogenesis. Circ Res 18:625–633

    Article  Google Scholar 

  • Girerd X, London G, Boutouyrie P, Mourad JJ, Safar M, Laurent S (1996) Remodeling of the radial artery in response to a chronic increase in shear stress. Hypertension 27:799–803

    Article  Google Scholar 

  • Go AS et al (2013) Executive summary: heart disease and stroke statistics-2013 update: a report from the American Heart Association. Circulation 127(1):143–152

    Article  Google Scholar 

  • Graham A (2003) Development of the pharyngeal arches. Am J Med Genet A 119A:251–256

    Article  Google Scholar 

  • Hogers B, DeRuiter MC, Gittenberger-de Groot AC, Poelmann RE (1999) Extraembryonic venous obstructions lead to cardiovascular malformations and can be embryolethal. Cardiovasc Res 41:87–99

    Article  Google Scholar 

  • Hove JR, Koster RW, Forouhar AS, Acevedo-Bolton G, Fraser SE, Gharib M (2003) Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421:172–177

    Article  Google Scholar 

  • Hu N, Clark EB (1989) Hemodynamics of the stage 12 to stage 29 chick embryo. Circ Res 65:1665–1670

    Article  Google Scholar 

  • Hu N, Christensen DA, Agrawal AK, Beaumont C, Clark EB, Hawkins JA (2009) Dependence of aortic arch morphogenesis on intracardiac blood flow in the left atrial ligated chick embryo. Anatomical record 292:652–660

    Article  Google Scholar 

  • Huang C, Sheikh F, Hollander M, Cai C, Becker D, Chu PH, Evans S, Chen J (2003) Embryonic atrial function is essential for mouse embryogenesis, cardiac morphogenesis and angiogenesis. Development 130:6111–6119

    Article  Google Scholar 

  • Humphrey JD, Rajagopal KR (2002) A constrained mixture model for growth and remodeling of soft tissues. Math Mod Meth Appl Sci 12:407–430

    Article  MATH  MathSciNet  Google Scholar 

  • Ilbawi AM et al (2007) Morphologic study of the ascending aorta and aortic arch in hypoplastic left hearts: surgical implications. J Thorac Cardiovasc Surg 134(1):99–105

    Article  Google Scholar 

  • Jaffee OC (1965) Hemodynamic factors in the development of the chick embryo heart. Anat Rec 151:69–75

    Article  Google Scholar 

  • Kamiya A, Togawa T (1980) Adaptive regulation of wall shear stress to flow change in the canine carotid artery. Am J Physiol 239:H14–21

    Google Scholar 

  • Kirby M (2002) Molecular embryogenesis of the heart. Pediatr Dev Pathol 5:516–543

  • Kirby ML, Hunt P, Wallis K, Thorogood P (1997) Abnormal patterning of the aortic arch arteries does not evoke cardiac malformations. Dev Dyn 208:34–47

    Article  Google Scholar 

  • Kowalski WJ, Teslovich NC, Dur O, Keller BB, Pekkan K (2012) Computational hemodynamic optimization predicts dominant aortic arch selection is driven by embryonic outflow tract orientation in the chick embryo. Biomech Model Mechanobiol 11:1057–1073

    Article  Google Scholar 

  • Kowalski WJ, Dur O, Wang Y, Patrick MJ, Tinney JP, Keller BB, Pekkan K (2013) Critical transitions in early embryonic aortic arch patterning and hemodynamics. PloS One 8:e60271

    Article  Google Scholar 

  • Langille BL (1996) Arterial remodeling: relation to hemodynamics. Can J Physiol Pharmacol 74:834–841

    Article  Google Scholar 

  • Langille BL, O’Donnell F (1986) Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 231:405–407

    Article  Google Scholar 

  • Le Lièvre CS, Le Douarin NM (1975) Mesenchymal derivatives of the neural crest: analysis of chimaeric quail and chick embryos. J Embryol Exp Morphol 34(1):125–154

  • le Noble F, Fleury V, Pries A, Corvol P, Eichmann A, Reneman RS (2005) Control of arterial branching morphogenesis in embryogenesis: go with the flow. Cardiovasc Res 65:619–628

    Article  Google Scholar 

  • Liu C, Liu W, Palie J, Lu MF, Brown NA, Martin JF (2002) Pitx2c patterns anterior myocardium and aortic arch vessels and is required for local cell movement into atrioventricular cushions. Development 129:5081–5091

    Article  Google Scholar 

  • Lucitti JL, Tobita K, Keller BB (2005) Arterial hemodynamics and mechanical properties after circulatory intervention in the chick embryo. J Exp Biol 208:1877–1885

    Article  Google Scholar 

  • Lucitti JL, Jones EA, Huang C, Chen J, Fraser SE, Dickinson ME (2007) Vascular remodeling of the mouse yolk sac requires hemodynamic force. Development 134:3317–3326

    Article  Google Scholar 

  • Macatee TL, Hammond BP, Arenkiel BR, Francis L, Frank DU, Moon AM (2003) Ablation of specific expression domains reveals discrete functions of ectoderm- and endoderm-derived FGF8 during cardiovascular and pharyngeal development. Development 130:6361–6374

    Article  Google Scholar 

  • May SR, Stewart NJ, Chang W, Peterson AS (2004) A Titin mutation defines roles for circulation in endothelial morphogenesis. Dev Biol 270:31–46

    Article  Google Scholar 

  • McElhinney DB, Tworetzky W, Lock JE (2010) Current status of fetal cardiac intervention. Circulation 121:1256–1263

    Article  Google Scholar 

  • Menon PG, Teslovich N, Chen CY, Undar A, Pekkan K (2013) Characterization of neonatal aortic cannula jet flow regimes for improved cardiopulmonary bypass. J Biomech 46:362–372

    Article  Google Scholar 

  • Molin DG, DeRuiter MC, Wisse LJ, Azhar M, Doetschman T, Poelmann RE, Gittenberger-de Groot AC (2002) Altered apoptosis pattern during pharyngeal arch artery remodelling is associated with aortic arch malformations in Tgfbeta2 knock-out mice. Cardiovasc Res 56:312–322

    Article  Google Scholar 

  • Molin DG, Poelmann RE, DeRuiter MC, Azhar M, Doetschman T, Gittenberger-de Groot AC (2004) Transforming growth factor beta-SMAD2 signaling regulates aortic arch innervation and development. Circ Res 95:1109–1117

    Article  Google Scholar 

  • Nishimura N et al (2006) Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke. Nat Methods 3(2):99–108

    Article  Google Scholar 

  • Pexieder T (1986) Standardized method for study of normal and abnormal cardiac development in chick, rat, mouse, dog and human embryos. Teratology 33:91C–92C

    Google Scholar 

  • Pologruto TA, Sabatini BL, Svoboda K (2003) ScanImage: flexible software for operating laser scanning microscopes. Biomed Eng Online 2–13

  • Reckova M, Rosengarten C, deAlmeida A, Stanley CP, Wessels A, Gourdie RG, Thompson RP, Sedmera D (2003) Hemodynamics is a key epigenetic factor in development of the cardiac conduction system. Circ Res 93:77–85

    Article  Google Scholar 

  • Rodbard S (1975) Vascular caliber. Cardiology 60:4–49

    Article  Google Scholar 

  • Roman BL, Pekkan K (2012) Mechanotransduction in embryonic vascular development. Biomech Model Mechanobiol 11:1149–1168

    Article  Google Scholar 

  • Rosenquist TH, Beall AC (1990) Elastogenic Cells in the Developing Cardiovascular System. Ann N Y Acad Sci 588(1 Embryonic Ori), 106–119. doi:10.1111/j.1749-6632.1990.tb13201.x

  • Rosenquist TH, McCoy JR, Waldo KL, Kirby ML (1988) Origin and propagation of elastogenesis in the developing cardiovascular system. Anat Rec 221(4):860–871. doi:10.1002/ar.1092210411

  • Rychter Z (1962) Experimental morphology of the aortic arches and the heart loop in chick embryos. In: Abercrombie M, Brachet J (eds) Advances in morphogenesis. Academic Press, New York, pp 333–371

    Google Scholar 

  • Rychter Z, Lemez L (1965) Changes in localization in aortic arches of laminar blood streams of main venous trunks to heart after exclusion of vitelline vessels on second day of incubation. Fed Proc Transl Suppl 24:815–820

    Google Scholar 

  • Sedmera D, Pexieder T, Rychterova V, Hu N, Clark EB (1999) Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions. Anat Rec 254:238–252

    Article  Google Scholar 

  • Taber LA (1998) A model for aortic growth based on fluid shear and fiber stresses. J Biomech Eng 120:348–354

    Article  Google Scholar 

  • Taber LA, Eggers DW (1996) Theoretical study of stress-modulated growth in the aorta. J Theor Biol 180:343–357

    Article  Google Scholar 

  • Thoma R (1893) Untersuchungen über die Histogenese und Histomechanik des Gefässsystems. Verlag von Ferdinand Enke, Stuttgart

    Google Scholar 

  • Tobita K, Garrison JB, Liu LJ, Tinney JP, Keller BB (2005) Three-dimensional myofiber architecture of the embryonic left ventricle during normal development and altered mechanical loads. Anat Rec A Discov Mol Cell Evol Biol 283:193–201

    Article  Google Scholar 

  • Ursem NT, Struijk PC, Poelmann RE, Wladimiroff JW (2001) Dorsal aortic flow velocity in chick embryos of stage 16 to 28. Ultrasound Med Biol 27:919–924

    Article  Google Scholar 

  • Valentin A, Humphrey JD, Holzapfel GA (2011) A multi-layered computational model of coupled elastin degradation, vasoactive dysfunction, and collagenous stiffening in aortic aging. Ann Biomed Eng 39:2027–2045

  • Vogel A, Venugopalan V (2003) Mechanisms of pulsed laser ablation of biological tissues. Chem Rev 103(2):577–644

    Article  Google Scholar 

  • Wagenseil JE (2010) A constrained mixture model for developing mouse aorta. Biomech Model Mechanobiol 10(5):671–87. doi:10.1007/s10237-010-0265-z

  • Waldo KL, Hutson MR, Ward CC, Zdanowicz M, Stadt HA, Kumiski D, Abu-Issa R, Kirby ML (2005) Secondary heart field contributes myocardium and smooth muscle to the arterial pole of the developing heart. Dev Biol 281:78–90

    Article  Google Scholar 

  • Waldo KL, Kirby ML (1993) Cardiac neural crest contribution to the pulmonary artery and sixth aortic arch artery complex in chick embryos aged 6 to 18 days. Anat Rec 237:385–399

    Article  Google Scholar 

  • Waldo KL, Kumiski D, Kirby ML (1996) Cardiac neural crest is essential for the persistence rather than the formation of an arch artery. Dev Dyn 205:281–292

    Article  Google Scholar 

  • Wang Y, Dur O, Patrick MJ, Tinney JP, Tobita K, Keller BB, Pekkan K (2009) Aortic arch morphogenesis and flow modeling in the chick embryo. Ann Biomed Eng 37:1069–1081

    Article  Google Scholar 

  • Yalcin HC, Shekhar A, Nishimura N, Rane AA, Schaffer CB, Butcher JT (2010a) Two-photon microscopy-guided femtosecond-laser photoablation of avian cardiogenesis: noninvasive creation of localized heart defects. Am J Physiol Heart Circ Physiol 299:H1728–1735

    Article  Google Scholar 

  • Yalcin HC, Shekhar A, Rane AA, Butcher JT (2010b) An ex-ovo chicken embryo culture system suitable for imaging and microsurgery applications. J Vis Exp (44):2154. doi:10.3791/2154

  • Yashiro K, Shiratori H, Hamada H (2007) Haemodynamics determined by a genetic programme govern asymmetric development of the aortic arch. Nature 450:285–288

    Article  Google Scholar 

  • Yoshigi M, Knott GD, Keller BB (2000) Lumped parameter estimation for the embryonic chick vascular system: a time-domain approach using MLAB. Comput Methods Programs Biomed 63:29–41

    Article  Google Scholar 

Download references

Acknowledgments

This research was supported by the National Institutes of Health (HL110328 to JTB), National Science Foundation (CBET-0955712 to JTB, graduate research fellowship to SEL) and European Research Council ERC STR Grant—Vascular Growth Project No. 307460 to KP.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Cornell University, 304 Weill Hall, Ithaca, NY, 14853-7202, USA

    Stephanie E. Lindsey, Akshay Shekhar, Nozomi Nishimura, Chris B. Schaffer & Jonathan T. Butcher

  2. Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA

    Prahlad G. Menon, William J. Kowalski & Kerem Pekkan

  3. Department of Mechanical Engineering, Dogus University, Istanbul, Turkey

    Huseyin C. Yalcin

  4. Department of Biomedical and Mechanical Engineering, Carnegie Mellon University, 700 Technology Dr, Pittsburgh, PA, 15219, USA

    Kerem Pekkan

Authors
  1. Stephanie E. Lindsey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prahlad G. Menon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William J. Kowalski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akshay Shekhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huseyin C. Yalcin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nozomi Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chris B. Schaffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jonathan T. Butcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kerem Pekkan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jonathan T. Butcher or Kerem Pekkan.

Additional information

This collaborative study is accomplished by joint lead authors (Stephanie E. Lindsey and Prahlad G. Menon) and by joint corresponding senior authors (Jonathan T. Butcher and Kerem Pekkan).

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lindsey, S.E., Menon, P.G., Kowalski, W.J. et al. Growth and hemodynamics after early embryonic aortic arch occlusion. Biomech Model Mechanobiol 14, 735–751 (2015). https://doi.org/10.1007/s10237-014-0633-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-014-0633-1

Keywords

Search

Navigation