Annals of Biomedical Engineering

, Volume 37, Issue 6, pp 1069–1081 | Cite as

Aortic Arch Morphogenesis and Flow Modeling in the Chick Embryo

  • Yajuan Wang
  • Onur Dur
  • Michael J. Patrick
  • Joseph P. Tinney
  • Kimimasa Tobita
  • Bradley B. Keller
  • Kerem Pekkan
Article
First Online:
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Accepted:

Abstract

Morphogenesis of the “immature symmetric embryonic aortic arches” into the “mature and asymmetric aortic arches” involves a delicate sequence of cell and tissue migration, proliferation, and remodeling within an active biomechanical environment. Both patient-derived and experimental animal model data support a significant role for biomechanical forces during arch development. The objective of the present study is to quantify changes in geometry, blood flow, and shear stress patterns (WSS) during a period of normal arch morphogenesis. Composite three-dimensional (3D) models of the chick embryo aortic arches were generated at the Hamburger–Hamilton (HH) developmental stages HH18 and HH24 using fluorescent dye injection, micro-CT, Doppler velocity recordings, and pulsatile subject-specific computational fluid dynamics (CFD). India ink and fluorescent dyes were injected into the embryonic ventricle or atrium to visualize right or left aortic arch morphologies and flows. 3D morphology of the developing great vessels was obtained from polymeric casting followed by micro-CT scan. Inlet aortic arch flow and cerebral-to-lower body flow split was obtained from 20 MHz pulsed Doppler velocity measurements and literature data. Statistically significant variations of the individual arch diameters along the developmental timeline are reported and correlated with WSS calculations from CFD. CFD simulations quantified pulsatile blood flow distribution from the outflow tract through the aortic arches at stages HH18 and HH24. Flow perfusion to all three arch pairs are correlated with the in vivo observations of common pharyngeal arch defect progression. The complex spatial WSS and velocity distributions in the early embryonic aortic arches shifted between stages HH18 and HH24, consistent with increased flow velocities and altered anatomy. The highest values for WSS were noted at sites of narrowest arch diameters. Altered flow and WSS within individual arches could be simulated using altered distributions of inlet flow streams. Thus, inlet flow stream distributions, 3D aortic sac and aortic arch geometries, and local vascular biologic responses to spatial variations in WSS are all likely to be important in the regulation of arch morphogenesis.

Keywords

Aortic arches Cardiac development Computational fluid dynamics (CFD) Congenital heart disease (CHD) Flow visualization Wall shear stress (WSS) 
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Notes

Acknowledgments

This research is supported by American Heart Association Beginning-Grant-in-Aid 0765284U (PI: Pekkan) and by the Children’s Hospital of Pittsburgh Foundation. Gratitude is expressed to Dr. Arvydas Usas for the micro-CT scanning. Dr. James Fitzpatrick, Dr. Greg Fisher, and Dr. Alan Waggoner provided valuable expertise on microscopy and fluorescent dye studies. We also acknowledge Pittsburgh Supercomputing Center Grant CCR080013 facilitating high-performance parallel CFD runs presented in this article.

Supplementary material

Supplementary material 1 (AVI 3260 kb)

References

  1. 1.
    Butcher, J., D. Sedmera, R. E. Guldberg, R. R. Markwald, 2006, “Quantitative volumetric analysis of cardiac morphogenesis assessed through micro-computed tomography,” Developmental Dynamics, 236(3), pp. 802–809. doi: 10.1002/dvdy.20962 CrossRefGoogle Scholar
  2. 2.
    Campbell, K. A., N. Hu, E. B. Clark, B. B. Keller, 1992, “Analysis of dynamic atrial dimension and function during early cardiac development in the chick embryo,” Pediatric Research, 32, pp. 333–337. doi: 10.1203/00006450-199209000-00018 PubMedCrossRefGoogle Scholar
  3. 3.
    Dintenfass, L., 1985, Blood Viscosity, Hyperviscosity and Hyperviscosaemia, MTP Press (Kluwer), London.Google Scholar
  4. 4.
    Even-Tzur, N., Y. Kloog, M. Wolf, and D. Elad (2008) Mucus secretion and cytoskeletal modifications in cultured nasal epithelial cells exposed to wall shear stresses. Biophys J 95:2998–3008. doi: 10.1529/biophysj.107.127142 PubMedCrossRefGoogle Scholar
  5. 5.
    Feintuch, A., P. Ruengsakulrach, A. Lin, J. Zhang, Y. Q. Zhou, J. Bishop, L. Davidson, D. Courtman, F. S. Foster, D. A. Steinman, R. M. Henkelman, C. R. Ethier 2007, “Hemodynamics in the mouse aortic arch as assessed by MRI, ultrasound, and numerical modeling,” Am. J. Physiol. Heart Circ. Physiol., 292, pp. H884-H892. doi: 10.1152/ajpheart.00796.2006 PubMedCrossRefGoogle Scholar
  6. 6.
    Frakes, D. H., M. J. Smith, J. Parks, S. Sharma, S. M. Fogel, A. P. Yoganathan 2005, “New techniques for the reconstruction of complex vascular anatomies from MRI images,” J Cardiovasc Magn Reson, 7(2), pp. 425–432. doi: 10.1081/JCMR-200053637 PubMedCrossRefGoogle Scholar
  7. 7.
    Gardiner, H., J. Brodszki, A. Eriksson, K. Marsál 2002, “Volume blood flow estimation in the normal and growth-restricted fetus,” Ultrasound Med Biol, 28(9), pp. 1107–1113. doi: 10.1016/S0301-5629(02)00565-3 PubMedCrossRefGoogle Scholar
  8. 8.
    Greve, J. M., A. S. Les, B. T. Tang, M. T. D. Blomme, N. M. Wilson, R. L. Dalman, N. J. Pelc, C. A. Taylor, 2006, “Allometric scaling of wall shear stress from mice to humans: quantification using cine phase-contrast MRI and computational fluid dynamics,” Am. J. Physiol. Heart Circ. Physiol., 291, pp. H1700-H1708. doi: 10.1152/ajpheart.00274.2006 PubMedCrossRefGoogle Scholar
  9. 9.
    Groenendijk, B. C. W., B. P. Hierck, A. C. Gittenberger-de Groot, R. E. Poelmann, 2003, “Development-related changes in the expression of shear stress responsive genes KLF-2, ET-1, and NOS-3 in the developing cardiovascular system of chicken embryos,” Dev. Dyn. 230, pp. 57–68. doi: 10.1002/dvdy.20029 CrossRefGoogle Scholar
  10. 10.
    Groenendijk, B. C. W., S. Stekelenburg-de Vos, P. Vennemann, J. W. Wladimiroff, F. T. M. Nieuwstadt, R. Lindken, J. Westerweel, B. P. Hierck, N. T. C. Ursem, and R. E. Poelmann (2008) The endothelin-1 pathway and the development of cardiovascular defects in the haemodynamically challenged chicken embryo. J Vasc Res 45:54–68. doi: 10.1159/000109077 PubMedCrossRefGoogle Scholar
  11. 11.
    Guldberg, R. E., C. L. Duvall, A. Peister, M. E. Oest, A. S. Lin, A. W. Palmer, M. E. Levenston 2008, “3D imaging of tissue integration with porous biomaterials,” Biomaterials, 29(28), pp. 3757–3761. doi: 10.1016/j.biomaterials.2008.06.018 PubMedCrossRefGoogle Scholar
  12. 12.
    Hamburger, V., H. L. Hamilton 1951, “A series of normal stages in the development of the chick embryo,” Journal of Morphology, 88(1), pp. 49–92. doi: 10.1002/jmor.1050880104 CrossRefGoogle Scholar
  13. 13.
    Himburg H. A., Dowd S. E., and Friedman M. H. (2007) Frequency-dependent response of the vascular endothelium to pulsatile shear stress. Am J Physiol Heart Circ Physiol 293(1):H645–653. doi: 10.1152/ajpheart.01087.2006 PubMedCrossRefGoogle Scholar
  14. 14.
    Hiruma, T., R. Hirakow, 1995, “Formation of the pharyngeal arch arteries in the chick embryo. Observations of corrosion casts by scanning electron microscopy,” Anat Embryol, 191, pp. 415–423. doi: 10.1007/BF00304427 PubMedCrossRefGoogle Scholar
  15. 15.
    Hiruma, T., Y. Nakajima, H. Nakamura, 2002, “Development of pharyngeal arch arteries in early mouse embryo,” J. Anat., 201, pp. 15–29. doi: 10.1046/j.1469-7580.2002.00071.x PubMedCrossRefGoogle Scholar
  16. 16.
    Hogers, B., M. C. DeRuiter, A. M. J. Baasten, A. C. Gittenberger-de Groot, R. E. Poelmann 1995, “Intracardiac blood flow patterns related to the yolk sac circulation of the chick embryo,” Circ. Res., 76, pp. 871–877.PubMedGoogle Scholar
  17. 17.
    Hogers, B., M. C. DeRuiter, A. C. Gittenberger-de Groot and R. E. Poelmann (1997) Unilateral vitelline vein ligation alters intracardiac blood flow patterns and morphogenesis in the chick embryo. Circ Res 80:473–481PubMedGoogle Scholar
  18. 18.
    Hogers, B., M. C. DeRuiter, A. C. Gittenberger-de Groot, R. E. Poelmann, 1999, “Extraembryonic venous obstructions lead to cardiovascular malformations and can be embryolethal,” Cardiovasc. Res., 41, pp. 87–99. doi: 10.1016/S0008-6363(98)00218-1 PubMedCrossRefGoogle Scholar
  19. 19.
    Hove, J. R., R. W. Koster, A. S. Forouhar, G. Acevedo-Bolton, S. E. Fraser, M. Gharib, 2003, “Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis,” Nature, 421, pp. 172–177. doi: 10.1038/nature01282 PubMedCrossRefGoogle Scholar
  20. 20.
    Hu, N., E. B. Clark, 1989, “Hemodynamics of the stage 12 to stage 29 chick embryo,” Circ Res., 65(6), pp. 1665–1670.PubMedGoogle Scholar
  21. 21.
    Hubbard, A. M., and Harty, P., 1999, “Prenatal magnetic resonance imaging of fetal anomalies,” Semin Roentgenol, 34(1), pp. 41–47. doi: 10.1016/S0037-198X(99)80019-4 PubMedCrossRefGoogle Scholar
  22. 22.
    Huo, Y. X. G., G. S. Kassab, 2008, “The flow field along the entire length of mouse aorta and primary branches,” Ann. Biomed. Eng. 36, pp. 685–699. doi: 10.1007/s10439-008-9473-4 PubMedCrossRefGoogle Scholar
  23. 23.
    Jin, S., J. Oshinski, D. P. Giddens, 2003, “Effects of wall motion and compliance on flow patterns in the ascending aorta,” J. Biomech. Eng. 125, pp. 347–354. doi: 10.1115/1.1574332 PubMedCrossRefGoogle Scholar
  24. 24.
    Kurihara, Y., H. Kurihara, H. Oda, K. Maemura, R. Nagai, T. Ishikawa, Y. Yazaki, 1995, “Aortic arch malformation and ventricular septal defect in mice deficient in endothelin-1,” J. Clin. Invest., 96, pp. 293–300. doi: 10.1172/JCI118033 PubMedCrossRefGoogle Scholar
  25. 25.
    Leuprecht, A., S. Kozerke, P. Boesiger, K. Perktold, 2003, “Blood flow in the human ascending aorta: a combined MRI and CFD study,” J. Eng. Math. 47, pp. 387–404. doi: 10.1023/B:ENGI.0000007969.18105.b7 CrossRefGoogle Scholar
  26. 26.
    Leyhane J. C. (1969) Visualization of blood streams in the developing chick heart. Anat. Rec. 163:312–313.Google Scholar
  27. 27.
    McQuinn, T. C., M. Bratoeva, A. de Almeida, M. Remond, R. P. Thompson, D. Sedmera, 2007, “High-frequency ultrasonographic imaging of Avian Cardiovascular Development,” Dev. Dyn. 236, pp. 3503–3513. doi: 10.1002/dvdy.21357 PubMedCrossRefGoogle Scholar
  28. 28.
    Morris, L., P. Delassus, A. Callanan, M. Walsh, F. Wallis, P. Grace, T. McGloughlin, 2005, “3-D numerical simulation of blood flow through models of the human aorta,” J. Biomech. Eng. 127, pp. 767–775. doi: 10.1115/1.1992521 PubMedCrossRefGoogle Scholar
  29. 29.
    Mujumdar, R. B., L. A. Ernst, S. R. Mujumdar, C. J. Lewis, A. S. Waggoner, 1993, “Cyanine dye labeling reagents: sulfoindocyanine succinimidyl esters,” Bioconjug Chem., 4(2), pp. 105–111. doi: 10.1021/bc00020a001 PubMedCrossRefGoogle Scholar
  30. 30.
    Ohno, M., Cooke, J. P., Dzau, V. J., and Gibbons, G. H., 1995, “Fluid shear stress induces endothelial transforming growth factor beta-1 transcription and production. Modulation by potassium channel blockade,” J Clin Invest, 95(3), pp. 1363-1369. doi: 10.1172/JCI117787 PubMedCrossRefGoogle Scholar
  31. 31.
    Pekkan, K., D. de Zélicourt, L. Ge, F. Sotiropoulos, D. Frakes, M. A. Fogel, A. P. Yoganathan 2005, “Physics-driven CFD modeling of complex anatomical cardiovascular flows—a TCPC case study,” Ann Biomed Eng., 33(3), pp. 284–300. doi: 10.1007/s10439-005-1731-0 PubMedCrossRefGoogle Scholar
  32. 32.
    Pekkan, K., L. P. Dasi, P. Nourparvar, S. Yerneni, K. Tobita, M. A. Fogel, B. B. Keller, A. Yoganathan, 2008, “In vitro hemodynamic investigation of the embryonic aortic arch at late gestation,” J. Biomech. 41, pp. 1697–1706. doi: 10.1016/j.jbiomech.2008.03.013 PubMedCrossRefGoogle Scholar
  33. 33.
    Pekkan, K., O. Dur, K. Kanter, K. Sundareswaran, M. Fogel, A. Yoganathan, and A. Ündar (2008) Neonatal aortic arch hemodynamics and perfusion during cardiopulmonary bypass. J Biomech Eng 130:061012.PubMedCrossRefGoogle Scholar
  34. 34.
    Peolma, C., P. Vennemann, R. Lindken, and J. Westerweel (2008) In vivo blood flow and wall shear stress measurements in the vitelline network. Exp Fluids 45:703–713CrossRefGoogle Scholar
  35. 35.
    Poelmann, R. E., A. C. Gittenberger-de Groot, B. P. Hierck, 2008, “The development of the heart and microcirculation: role of shear stress,” Med Biol Eng Comput, 46, pp. 479–484. doi: 10.1007/s11517-008-0304-4 PubMedCrossRefGoogle Scholar
  36. 36.
    Ravnic, D. J., Y. Z. Zhang, A. Tsuda, J. P. Pratt, H. T. Huss, S. J. Mentzer, 2006, “Multi-image particle tracking velocimetry of the microcirculation using fluorescent nanoparticles,” Microvasc. Res. 72, pp. 27–33. doi: 10.1016/j.mvr.2006.04.006 PubMedCrossRefGoogle Scholar
  37. 37.
    Romanoff, A., 1961, Avian Embryo, Structural and Functional Development, Macmillan.Google Scholar
  38. 38.
    Rudolph, A. M., M. A. Heymann 1970, “Circulatory changes during growth in the fetal lamb,” Circ Res., 26(3), pp. 289–299.PubMedGoogle Scholar
  39. 39.
    Sadler T. W. (2005) Langman’s Medical Embryology. Lippincott Williams, Philadelphia, pp. 159–194Google Scholar
  40. 40.
    Schleich, J.-M., Pontchaillou, C. A., Dillenseger, J.-L., and Coatrieux, J.-L. (2002) Understanding normal cardiac development using animated models. IEEE Comput Graph Appl 22(1):14–19. doi: 10.1109/38.974513 CrossRefGoogle Scholar
  41. 41.
    Sims, P. J., A. S. Waggoner, C.-H. Wang, J. F. Hoffman, 1974, “Studies on mechanism by which cyanine dyes measure membrane-potential in red blood-cells and phosphatidylcholine vesicles,” Biochemistry, 13(16), pp. 3315–3330. doi: 10.1021/bi00713a022 PubMedCrossRefGoogle Scholar
  42. 42.
    Suo, J., D. E. Ferrara, E. Sorescu, R. E. Guldberg, W. R. Taylor, and D. P. Giddens (2007) Hemodynamic shear stress in mouse aortas implications for atherogenesis. Arterioscler Thromb Vasc Biol 27:346–351. doi: 10.1161/01.ATV.0000253492.45717.46 PubMedCrossRefGoogle Scholar
  43. 43.
    Taber, L. A., N. Hu, T. Pexieder, E. B. Clark, B. B. Keller 1993, “Residual strain in the ventricle of the stage 16–24 chick embryo.,” Circ Res 72(2):455–462.PubMedGoogle Scholar
  44. 44.
    Ursell, P. C., J. M. Byrne, T. R. Fears, B. A. Strobino, W. M. Gersony 1991, “Growth of the great vessels in the normal human fetus and in the fetus with cardiac defects,” Circulation, 84(5), pp. 2028–2033.PubMedGoogle Scholar
  45. 45.
    Vennemann, P., K. T. Kiger, R. Lindken, B. C. W. Groenendijk, S. Stekelenburg-de Vos, T. L. M. ten Hagen, N. T. C. Ursem, R. E. Poelmann, J. Westerweel, B. P. Hierck, 2006, “In vivo micro particle image velocimetry measurements of blood-plasma in the embryonic avian heart,” J. Biomech. 39, pp. 1191–1200. doi: 10.1016/j.jbiomech.2005.03.015 PubMedCrossRefGoogle Scholar
  46. 46.
    Waldo, K. L., M. R. Hutson, C.C. Ward, M. Zdanowicz, H. A. Stadt, D. Kumiski, R. Abu-Issa, M. L. Kirby 2005, “Secondary heart field contributes myocardium and smooth muscle to the arterial pole of the developing heart,” Dev. Biol. 281, pp. 78–90. doi: 10.1016/j.ydbio.2005.02.012 PubMedCrossRefGoogle Scholar
  47. 47.
    Wang, C., K. Pekkan, D. de Zelicourt, A. Parihar, A. Kulkarni, M. Horner, A. P. Yoganathan 2007, “Progress in the CFD Modeling of Flow Instability in Anatomical Total Cavopulmonary Connections,” Ann. Biomed. Eng. 35(11), pp. 1840–1856. doi: 10.1007/s10439-007-9356-0 PubMedCrossRefGoogle Scholar
  48. 48.
    Yoshida, H., F. Manasek, R. A. Arcilla, 1983, “Intracardiac flow patterns in early embryonic life., “Circ. Res., 53, pp. 363–371PubMedGoogle Scholar
  49. 49.
    Yoshigi, M., Knott, G. D., Keller, B. B., 2000, “Lumped parameter estimation for the embryonic chick vascular system: a time-domain approach using MLAB,” Comput. Methods Programs Biomed. 63, pp. 29–41. doi: 10.1016/S0169-2607(00)00061-4 PubMedCrossRefGoogle Scholar
  50. 50.
    20. Young, S., Kretlow, J. D., Nguyen, C., Bashoura, A. G., Baggett, L. S., Jansen, J. A., Wong, M., and Mikos, A. G. (2008) Microcomputed tomography characterization of neovascularization in bone tissue engineering application. Tissue Eng Part B Rev 14:295–306PubMedCrossRefGoogle Scholar
  51. 51.
    Zamir, M., P. Sinclair, T. H. Wonnacott 1992, “Relation between diameter and flow in major branches of the arch of the aorta,” J Biomech, 25(11), pp. 1303–1310. doi: 10.1016/0021-9290(92)90285-9 PubMedCrossRefGoogle Scholar
  52. 52.
    Ziegler T., Bouzourène K., Harrison V. J., Brunner H. R., and Hayoz D. (1998) Influence of oscillatory and unidirectional flow environments on the expression of endothelin and nitric oxide synthase in cultured endothelial cells. Arterioscler Thromb Vasc Biol. 18(5):686–692PubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2009

Authors and Affiliations

  • Yajuan Wang
    • 1
  • Onur Dur
    • 1
  • Michael J. Patrick
    • 2
  • Joseph P. Tinney
    • 3
  • Kimimasa Tobita
    • 3
    • 4
  • Bradley B. Keller
    • 1
    • 3
    • 4
  • Kerem Pekkan
    • 1
  1. 1.Department of Biomedical EngineeringCarnegie Mellon UniversityPittsburghUSA
  2. 2.Molecular Biosensor and Imaging CenterCarnegie Mellon UniversityPittsburghUSA
  3. 3.Department of PediatricsUniversity of PittsburghPittsburghUSA
  4. 4.Department of BioengineeringUniversity of PittsburghPittsburghUSA

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