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Annals of Biomedical Engineering

, Volume 40, Issue 10, pp 2212–2227 | Cite as

Computational Fluid Dynamics of Developing Avian Outflow Tract Heart Valves

  • Koonal N. Bharadwaj
  • Cassie Spitz
  • Akshay Shekhar
  • Huseyin C. Yalcin
  • Jonathan T. ButcherEmail author
Article

Abstract

Hemodynamic forces play an important role in sculpting the embryonic heart and its valves. Alteration of blood flow patterns through the hearts of embryonic animal models lead to malformations that resemble some clinical congenital heart defects, but the precise mechanisms are poorly understood. Quantitative understanding of the local fluid forces acting in the heart has been elusive because of the extremely small and rapidly changing anatomy. In this study, we combine multiple imaging modalities with computational simulation to rigorously quantify the hemodynamic environment within the developing outflow tract (OFT) and its eventual aortic and pulmonary valves. In vivo Doppler ultrasound generated velocity profiles were applied to Micro-Computed Tomography generated 3D OFT lumen geometries from Hamburger–Hamilton (HH) stage 16–30 chick embryos. Computational fluid dynamics simulation initial conditions were iterated until local flow profiles converged with in vivo Doppler flow measurements. Results suggested that flow in the early tubular OFT (HH16 and HH23) was best approximated by Poiseuille flow, while later embryonic OFT septation (HH27, HH30) was mimicked by plug flow conditions. Peak wall shear stress (WSS) values increased from 18.16 dynes/cm2 at HH16 to 671.24 dynes/cm2 at HH30. Spatiotemporally averaged WSS values also showed a monotonic increase from 3.03 dynes/cm2 at HH16 to 136.50 dynes/cm2 at HH30. Simulated velocity streamlines in the early heart suggest a lack of mixing, which differed from classical ink injections. Changes in local flow patterns preceded and correlated with key morphogenetic events such as OFT septation and valve formation. This novel method to quantify local dynamic hemodynamics parameters affords insight into sculpting role of blood flow in the embryonic heart and provides a quantitative baseline dataset for future research.

Keywords

Shear stress Blood flow Mechanotransduction Morphogenesis Pulmonary valve Aortic valve Embryo Mechanobiology Finite element Simulation 

Abbreviations

OFT

Outflow tract

EndMT

Endocardial-to-mesenchymal transformation

CHD

Congenital heart defects

CFD

Computational fluid dynamics

Micro-CT

Micro-computed tomography

WSS

Wall shear stress

ECs

Endothelial cells

LVOFT

Left ventricular outflow tract

RVOFT

Right ventricular outflow tract

CTB

Conotruncal banding

Notes

Acknowledgments

This research was supported in part by grants from the American Heart Association (0830384 N, to J.T.B), National Institutes of Health (HL110328, to JTB), the Leducq Foundation (JTB), The Hartwell Foundation (JTB), European Union Seventh Framework Marie Curie Actions International Reintegration Program (IRG-276987 to HCY), and Dogus University (BAP-2010_11_D1-07 to HCY). HCY thanks to Prof. Dr. Ahmet Ceranoglu, Mechanical Engineering Department Head at Dogus University for his support of collaborative works with Cornell University.

Supplementary material

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Supplementary material 1 (MPEG 5465 kb)
10439_2012_574_MOESM2_ESM.mpeg (3.6 mb)
Supplementary material 2 (MPEG 3702 kb)

References

  1. 1.
    Bajolle, F., S. Zaffran, R. G. Kelly, J. Hadchouel, D. Bonnet, N. A. Brown, and M. E. Buckingham. Rotation of the myocardial wall of the outflow tract is implicated in the normal positioning of the great arteries. Circ. Res. 98:421–428, 2006.PubMedCrossRefGoogle Scholar
  2. 2.
    Birchall, D., A. Zaman, J. Hacker, G. Davies, and D. Mendelow. Analysis of haemodynamic disturbance in the atherosclerotic carotid artery using computational fluid dynamics. Eur. Radiol. 16:1074–1083, 2006.PubMedCrossRefGoogle Scholar
  3. 3.
    Bove, E. L., F. Migliavacca, M. R. de Leval, R. Balossino, G. Pennati, T. R. Lloyd, S. Khambadkone, T. Y. Hsia, and G. Dubini. Use of mathematic modeling to compare and predict hemodynamic effects of the modified Blalock-Taussig and right ventricle-pulmonary artery shunts for hypoplastic left heart syndrome. J. Thorac. Cardiovasc. Surg. 136:312–320.e2, 2008.Google Scholar
  4. 4.
    Buskohl, P. R., R. A. Gould, and J. T. Butcher. Quantification of embryonic atrioventricular valve biomechanics during morphogenesis. J. Biomech., 2011.Google Scholar
  5. 5.
    Butcher, J. T., D. Sedmera, R. E. Guldberg, and R. R. Markwald. Quantitative volumetric analysis of cardiac morphogenesis assessed through micro-computed tomography. Dev. Dyn. 236:802–809, 2007.PubMedCrossRefGoogle Scholar
  6. 6.
    Caro, C. G., J. M. Fitz-Gerald, and R. C. Schroter. Atheroma and arterial wall shear. Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis. Proc. R. Soc. Lond. B. Biol. Sci. 177:109–159, 1971.Google Scholar
  7. 7.
    Clark, E. B., and N. Hu. Developmental hemodynamic changes in the chick embryo from stage 18 to 27. Circ. Res. 51:810–815, 1982.PubMedCrossRefGoogle Scholar
  8. 8.
    Clark, E. B., N. Hu, and G. C. Rosenquist. Effect of conotruncal constriction on aortic-mitral valve continuity in the stage 18, 21 and 24 chick embryo. Am. J. Cardiol. 53:324–327, 1984.PubMedCrossRefGoogle Scholar
  9. 9.
    Colvee, E., and J. M. Hurle. Malformations of the semilunar valves produced in chick embryos by mechanical interference with cardiogenesis. An experimental approach to the role of hemodynamics in valvular development. Anat. Embryol. (Berl) 168:59–71, 1983.Google Scholar
  10. 10.
    Cruz, M. D., and R. Markward (eds.). Living Morphogenesis of the Heart. Boston: Birkhäuser, 1998.Google Scholar
  11. 11.
    Culver, J. C., and M. E. Dickinson. The effects of hemodynamic force on embryonic development. Microcirculation 17:164–178, 2010.PubMedCrossRefGoogle Scholar
  12. 12.
    deAlmeida, A., T. McQuinn, and D. Sedmera. Increased ventricular preload is compensated by myocyte proliferation in normal and hypoplastic fetal chick left ventricle. Circ. Res. 100:1363–1370, 2007.Google Scholar
  13. 13.
    DeGroff, C. G., B. L. Thornburg, J. O. Pentecost, K. L. Thornburg, M. Gharib, D. J. Sahn, and A. Baptista. Flow in the early embryonic human heart: a numerical study. Pediatr. Cardiol. 24:375–380, 2003.PubMedCrossRefGoogle Scholar
  14. 14.
    Forouhar, A. S., M. Liebling, A. Hickerson, A. Nasiraei-Moghaddam, H. J. Tsai, J. R. Hove, S. E. Fraser, M. E. Dickinson, and M. Gharib. The embryonic vertebrate heart tube is a dynamic suction pump. Science 312:751–753, 2006.PubMedCrossRefGoogle Scholar
  15. 15.
    Fry, D. L. Acute vascular endothelial changes associated with increased blood velocity gradients. Circ. Res. 22:165–197, 1968.PubMedCrossRefGoogle Scholar
  16. 16.
    Galindo, A., A. Mendoza, J. Arbues, A. Graneras, D. Escribano, and O. Nieto. Conotruncal anomalies in fetal life: accuracy of diagnosis, associated defects and outcome. Eur. J. Obstet. Gynecol. Reprod. Biol. 146:55–60, 2009.PubMedCrossRefGoogle Scholar
  17. 17.
    Gomez-Fifer, C. Hypoplastic left heart syndrome in the fetus: diagnostic features prior to birth and their impact on postnatal outcome. Prog. Ped. Card. 22:53–60, 2006.Google Scholar
  18. 18.
    Groenendijk, B. C., B. P. Hierck, J. Vrolijk, M. Baiker, M. J. Pourquie, A. C. Gittenberger-de Groot, and R. E. Poelmann. Changes in shear stress-related gene expression after experimentally altered venous return in the chicken embryo. Circ. Res. 96:1291–1298, 2005.Google Scholar
  19. 19.
    Henning, A. L., M. X. Jiang, H. C. Yalcin, and J. T. Butcher. Quantitative three-dimensional imaging of live avian embryonic morphogenesis via micro-computed tomography. Dev. Dyn. 240:1949–1957, 2011.PubMedCrossRefGoogle Scholar
  20. 20.
    Hierck, B. P., K. Van der Heiden, C. Poelma, J. Westerweel, and R. E. Poelmann. Fluid shear stress and inner curvature remodeling of the embryonic heart. Choosing the right lane!. ScientificWorldJournal 8:212–222, 2008.PubMedCrossRefGoogle Scholar
  21. 21.
    Hoffman, J. I. Incidence of congenital heart disease: II. Prenatal incidence. Pediatr. Cardiol. 16:155–165, 1995.PubMedCrossRefGoogle Scholar
  22. 22.
    Hoffman, J. I., and S. Kaplan. The incidence of congenital heart disease. J. Am. Coll. Cardiol. 39:1890–1900, 2002.PubMedCrossRefGoogle Scholar
  23. 23.
    Hogers, B., M. C. DeRuiter, A. M. Baasten, A. C. Gittenberger-de Groot, and R. E. Poelmann. Intracardiac blood flow patterns related to the yolk sac circulation of the chick embryo. Circ. Res. 76:871–877, 1995.Google Scholar
  24. 24.
    Hu, N., and E. B. Clark. Hemodynamics of the stage 12 to stage 29 chick embryo. Circ. Res. 65:1665–1670, 1989.PubMedCrossRefGoogle Scholar
  25. 25.
    Hu, N., D. A. Christensen, A. K. Agrawal, C. Beaumont, E. B. Clark, and J. A. Hawkins. Dependence of aortic arch morphogenesis on intracardiac blood flow in the left atrial ligated chick embryo. Anat. Rec. (Hoboken) 292:652–660, 2009.CrossRefGoogle Scholar
  26. 26.
    Ilbawi, A. M., D. E. Spicer, S. Bharati, A. Cook, and R. H. Anderson. Morphologic study of the ascending aorta and aortic arch in hypoplastic left hearts: surgical implications. J. Thorac. Cardiovasc. Surg. 134:99–105, 2007.PubMedCrossRefGoogle Scholar
  27. 27.
    Jones, E. A., M. H. Baron, S. E. Fraser, and M. E. Dickinson. Measuring hemodynamic changes during mammalian development. Am. J. Physiol. Heart Circ. Physiol. 287:H1561–H1569, 2004.PubMedCrossRefGoogle Scholar
  28. 28.
    Kim, J. S., J. Min, A. K. Recknagel, M. Riccio, and J. T. Butcher. Quantitative three-dimensional analysis of embryonic chick morphogenesis via microcomputed tomography. Anat. Rec. (Hoboken) 294:1–10, 2011.CrossRefGoogle Scholar
  29. 29.
    Kirby, M. L. Molecular embryogenesis of the heart. Pediatr. Dev. Pathol. 5:516–543, 2002.PubMedCrossRefGoogle Scholar
  30. 30.
    Lammer, E. J., J. S. Chak, D. M. Iovannisci, K. Schultz, K. Osoegawa, W. Yang, S. L. Carmichael, and G. M. Shaw. Chromosomal abnormalities among children born with conotruncal cardiac defects. Birth Defects Res. A. Clin. Mol. Teratol. 85:30–35, 2009.Google Scholar
  31. 31.
    Lawson, N. D., and B. M. Weinstein. Arteries and veins: making a difference with zebrafish. Nat. Rev. Genet. 3:674–682, 2002.PubMedCrossRefGoogle Scholar
  32. 32.
    le Noble, F., V. Fleury, A. Pries, P. Corvol, A. Eichmann, and R. S. Reneman. Control of arterial branching morphogenesis in embryogenesis: go with the flow. Cardiovasc. Res. 65:619–628, 2005.PubMedCrossRefGoogle Scholar
  33. 33.
    Lenz, F., and R. Chaoui. Changes in pulmonary venous Doppler parameters in fetal cardiac defects. Ultrasound Obstet. Gynecol. 28:63–70, 2006.PubMedCrossRefGoogle Scholar
  34. 34.
    Liu, A., A. Nickerson, A. Troyer, X. Yin, R. Cary, K. Thornburg, R. Wang, and S. Rugonyi. Quantifying blood flow and wall shear stresses in the outflow tract of chick embryonic hearts. Comput. Struct. 89:855–867, 2011.PubMedCrossRefGoogle Scholar
  35. 35.
    Liu, A., S. Rugonyi, J. O. Pentecost, and K. L. Thornburg. Finite element modeling of blood flow-induced mechanical forces in the outflow tract of chick embryonic hearts. Comput. Struct. 85:727–738, 2007.CrossRefGoogle Scholar
  36. 36.
    McQuinn, T. C., M. Bratoeva, A. Dealmeida, M. Remond, R. P. Thompson, and D. Sedmera. High-frequency ultrasonographic imaging of avian cardiovascular development. Dev. Dyn. 236:3503–3513, 2007.PubMedCrossRefGoogle Scholar
  37. 37.
    Mjaatvedt, C. H., T. Nakaoka, R. Moreno-Rodriguez, R. A. Norris, M. J. Kern, C. A. Eisenberg, D. Turner, and R. R. Markwald. The outflow tract of the heart is recruited from a novel heart-forming field. Dev. Biol. 238:97–109, 2001.PubMedCrossRefGoogle Scholar
  38. 38.
    Olesen, S. P., D. E. Clapham, and P. F. Davies. Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331:168–170, 1988.PubMedCrossRefGoogle Scholar
  39. 39.
    Oosterbaan, A. M., N. T. Ursem, P. C. Struijk, J. G. Bosch, A. F. van der Steen, and E. A. Steegers. Doppler flow velocity waveforms in the embryonic chicken heart at developmental stages corresponding to 5-8 weeks of human gestation. Ultrasound Obstet. Gynecol. 33:638–644, 2009.PubMedCrossRefGoogle Scholar
  40. 40.
    Pierpont, M. E., C. T. Basson, D. W. Benson, Jr., B. D. Gelb, T. M. Giglia, E. Goldmuntz, G. McGee, C. A. Sable, D. Srivastava, C. L. Webb, and American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young. Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation 115:3015–3038, 2007.Google Scholar
  41. 41.
    Poelma, C., K. Van der Heiden, B. P. Hierck, R. E. Poelmann, and J. Westerweel. Measurements of the wall shear stress distribution in the outflow tract of an embryonic chicken heart. J. R. Soc. Interface 7:91–103, 2010.PubMedCrossRefGoogle Scholar
  42. 42.
    Qayyum, S. R., S. Webb, R. H. Anderson, F. J. Verbeek, N. A. Brown, and M. K. Richardson. Septation and valvar formation in the outflow tract of the embryonic chick heart. Anat. Rec. 264:273–283, 2001.PubMedCrossRefGoogle Scholar
  43. 43.
    Rothenberg, F., S. A. Fisher, and M. Watanabe. Sculpting the cardiac outflow tract. Birth Defects Res. C. Embryo. Today 69:38–45, 2003.PubMedCrossRefGoogle Scholar
  44. 44.
    Sedmera, D., T. Pexieder, V. Rychterova, N. Hu, and E. B. Clark. Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions. Anat. Rec. 254:238–252, 1999.PubMedCrossRefGoogle Scholar
  45. 45.
    Sivanandam, S., J. S. Glickstein, B. F. Printz, L. D. Allan, K. Altmann, D. E. Solowiejczyk, L. Simpson, A. Perez-Delboy, and C. S. Kleinman. Prenatal diagnosis of conotruncal malformations: diagnostic accuracy, outcome, chromosomal abnormalities, and extracardiac anomalies. Am. J. Perinatol. 23:241–245, 2006.PubMedCrossRefGoogle Scholar
  46. 46.
    Srivastava, D., and E. N. Olson. A genetic blueprint for cardiac development. Nature 407:221–226, 2000.PubMedCrossRefGoogle Scholar
  47. 47.
    Tanner, K., N. Sabrine, and C. Wren. Cardiovascular malformations among preterm infants. Pediatrics 116:e833–e838, 2005.PubMedCrossRefGoogle Scholar
  48. 48.
    Towbin, J. A., and J. Belmont. Molecular determinants of left and right outflow tract obstruction. Am. J. Med. Genet. 97:297–303, 2000.PubMedCrossRefGoogle Scholar
  49. 49.
    Vennemann, P., K. T. Kiger, R. Lindken, B. C. Groenendijk, S. Stekelenburg-de Vos, T. L. ten Hagen, N. T. Ursem, R. E. Poelmann, J. Westerweel, and B. P. Hierck. In vivo micro particle image velocimetry measurements of blood-plasma in the embryonic avian heart. J. Biomech. 39:1191–1200, 2006.PubMedCrossRefGoogle Scholar
  50. 50.
    Vermot, J., A. S. Forouhar, M. Liebling, D. Wu, D. Plummer, M. Gharib, and S. E. Fraser. Reversing blood flows act through klf2a to ensure normal valvulogenesis in the developing heart. PLoS Biol. 7:e1000246, 2009.PubMedCrossRefGoogle Scholar
  51. 51.
    Wang, Y., O. Dur, M. J. Patrick, J. P. Tinney, K. Tobita, B. B. Keller, and K. Pekkan. Aortic arch morphogenesis and flow modeling in the chick embryo. Ann. Biomed. Eng. 37:1069–1081, 2009.PubMedCrossRefGoogle Scholar
  52. 52.
    Weinstein, B. M., D. L. Stemple, W. Driever, and M. C. Fishman. Gridlock, a localized heritable vascular patterning defect in the zebrafish. Nat. Med. 1:1143–1147, 1995.PubMedCrossRefGoogle Scholar
  53. 53.
    Wilcox, D. C. Basic Fluid Mechanics. La Caftada, CA: DCW Industries, Inc., 1997.Google Scholar
  54. 54.
    Yalcin, H. C., A. Shekhar, A. A. Rane, and J. T. Butcher. An ex-ovo chicken embryo culture system suitable for imaging and microsurgery applications. J. Vis. Exp. 44. pii:2154. doi: 10.3791/2154, 2010.
  55. 55.
    Yalcin, H. C., A. Shekhar, N. Nishimura, A. A. Rane, C. B. Schaffer, and J. T. Butcher. Two-photon microscopy-guided femtosecond-laser photoablation of avian cardiogenesis: noninvasive creation of localized heart defects. Am. J. Physiol. Heart Circ. Physiol. 299:H1728–H1735, 2010.PubMedCrossRefGoogle Scholar
  56. 56.
    Yalcin, H. C., A. Shekhar, T. C. McQuinn, and J. T. Butcher. Hemodynamic patterning of the avian atrioventricular valve. Dev. Dyn. 240:23–35, 2011.PubMedCrossRefGoogle Scholar
  57. 57.
    Yashiro, K., H. Shiratori, and H. Hamada. Haemodynamics determined by a genetic programme govern asymmetric development of the aortic arch. Nature 450:285–288, 2007.PubMedCrossRefGoogle Scholar
  58. 58.
    Yelbuz, T. M., K. L. Waldo, X. Zhang, M. Zdanowicz, J. Parker, T. L. Creazzo, G. A. Johnson, and M. L. Kirby. Myocardial volume and organization are changed by failure of addition of secondary heart field myocardium to the cardiac outflow tract. Dev. Dyn. 228:152–160, 2003.PubMedCrossRefGoogle Scholar
  59. 59.
    Yoshida, H., F. Manasek, and R. A. Arcilla. Intracardiac flow patterns in early embryonic life. A reexamination. Circ. Res. 53:363–371, 1983.PubMedCrossRefGoogle Scholar
  60. 60.
    Zamir, E. A., V. Srinivasan, R. Perucchio, and L. A. Taber. Mechanical asymmetry in the embryonic chick heart during looping. Ann. Biomed. Eng. 31:1327–1336, 2003.PubMedCrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2012

Authors and Affiliations

  • Koonal N. Bharadwaj
    • 1
  • Cassie Spitz
    • 1
  • Akshay Shekhar
    • 1
  • Huseyin C. Yalcin
    • 2
  • Jonathan T. Butcher
    • 1
    Email author
  1. 1.Department of Biomedical EngineeringCornell UniversityIthacaUSA
  2. 2.Department of Mechanical EngineeringDogus UniversityIstanbulTurkey

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