Computational Model for Early Cardiac Looping

  • Ashok Ramasubramanian
  • Kimberly S. Latacha
  • Jessica M. Benjamin
  • Dmitry A. Voronov
  • Arvind Ravi
  • Larry A. Taber
Article
First Online:
Received:
Accepted:

Looping is a vital event during early cardiac morphogenesis, as the initially straight heart tube bends and twists into a curved tube, laying out the basic pattern of the future four-chambered heart. Despite intensive study for almost a century, the biophysical mechanisms that drive this process are not well understood. To explore a recently proposed hypothesis for looping, we constructed a finite element model for the embryonic chick heart during the first phase of looping, called c-looping. The model includes the main structures of the early heart (heart tube, omphalomesenteric veins, and dorsal mesocardium), and the analysis features realistic three-dimensional geometry, nonlinear passive and active material properties, and anisotropic growth. As per our earlier hypothesis for c-looping, actin-based morpho-genetic processes (active cell shape change, cytoskeletal contraction, and cell migration) are simulated in specific regions of the model. The model correctly predicts the initial gross morphological shape changes of the heart, as well as distributions of morphogenetic stresses and strains measured in embryonic chick hearts. The model was tested further in studies that perturbed normal cardiac morphogenesis. The model, taken together with the new experimental data, supports our hypothesis for the mechanisms that drive early looping.

Keywords

Chick embryo Heart development Finite element modeling Morphogenesis 
This is a preview of subscription content, log in to check access.

Notes

ACKNOWLEDGMENTS

The authors would like to thank Dr. Elliot Fried for help with deriving the material Jacobian when the Jaumann rate is used (for UMAT), Drs. Edward Sptiznagel and Ray Koopman for assistance with calculating the standard error of the mean for cumulative strains, Dr. Barna Szabo for his helpful suggestions to improve the accuracy of the finite element simulation, Mathieu Rémond and Nandan Nerurkar for help with experimental data collection, and Patrick Alford and Gang Xu for assistance with model development. This work was supported by the NIH grants F32 HL79764 (AR), R01 HL64347 (LAT), and T32 HL07916 (KSL, training grant awarded to Department of Biomedical Engineering; PI: F.C.P. Yin).

REFERENCES

  1. 1.
    Alford, P. W. and L. A. Taber. Regional epicardial strain in the embryonic chick heart during the early looping stages. J. Biomech. 36:1135–1141, 2003.CrossRefPubMedGoogle Scholar
  2. 2.
    Baldwin, H. S., and M. Solursh. Degradation of hyaluronic acid does not prevent looping of the mammalian heart in situ. Dev. Biol. 136:555–559, 1989.CrossRefPubMedGoogle Scholar
  3. 3.
    Beers, Y. Introduction to the Theory of Error. Reading, MA: Addison Wesley, 1953.Google Scholar
  4. 4.
    de la Cruz, M. V., and C. Sanchez-Gomez. Straight heart tube. Primitive cardiac cavities vs. primitive cardiac segments. In: Living Morphogenesis of the Heart, edited by M. V. de la Cruz and R. R. Markwald. Boston: Birkhauser, 1998, pp. 85–98.Google Scholar
  5. 5.
    Hamburger, V., and H. L. Hamilton. A series of normal stages in the development of the chick embryo. J. Morphol. 88:49–92, 1951.CrossRefGoogle Scholar
  6. 6.
    Harvey, R. P. Cardiac looping—an uneasy deal with laterality. Semin. Cell Dev. Biol. 9:101–108, 1998.CrossRefPubMedGoogle Scholar
  7. 7.
    Hashima, A. R., A. A. Young, A. D. McCulloch, and L. K. Waldman. Nonhomogeneous analysis of epicardial strain distributions during acute myocardial ischemia in the dog. J. Biomech. 26:19–35, 1993.CrossRefPubMedGoogle Scholar
  8. 8.
    Hiruma, T., and R. Hirakow. An ultrastructural topographical study on myofibrillogenesis in the heart of the chick embryo during pulsation onset period. Anat. Embryol. 172:325–329, 1985.CrossRefPubMedGoogle Scholar
  9. 9.
    Itasaki, N., H. Nakamura, H. Sumida, and M. Yasuda. Actin bundles on the right side in the caudal part of the heart tube play a role in dextro-looping in the embryonic chick heart. Anat. Embryol. 183:29–39, 1991.CrossRefPubMedGoogle Scholar
  10. 10.
    Itasaki, N., H. Nakamura, and M. Yasuda. Changes in the arrangement of actin bundles during heart looping in the chick embryo. Anat. Embryol. 180:413–420, 1989.CrossRefPubMedGoogle Scholar
  11. 11.
    Koushik, S. V., J. Wang, R. Rogers, D. Moskophidis, N. A. Lambert, T. L. Creazzo, and S. J. Conway. Targeted inactivation of the sodium-calcium exchanger (Ncx1) results in the lack of a heartbeat and abnormal myofibrillar organization. FASEB J. 15:1209–1211, 2001.PubMedGoogle Scholar
  12. 12.
    Lacktis, J. W., and F. J. Manasek. An Analysis of Deformation During a Normal Morphogenic Event. In: Morphogenesis and Malformation of the Cardiovascular System, edited by G. C. Rosenquist and D. Bergsma. New York: Alan R. Liss, 1978, pp. 205–227.Google Scholar
  13. 13.
    Latacha, K. S., M. C. Remond, A. Ramasubramanian, A. Y. Chen, E. L. Elson, and L. A. Taber. The role of actin polymerization in bending of the early heart tube. Dev. Dyn. 233:1272–1286, 2005.CrossRefPubMedGoogle Scholar
  14. 14.
    Manasek, F. J. Control of early embryonic heart morphogenesis: a hypothesis. In: Development of the Vascular System, edited by J. Nugent and M. O’Connor. London: Pitman, 1983, pp. 4–19.Google Scholar
  15. 15.
    Manasek, F. J., M. B. Burnside, and R. E. Waterman. Myocardial cell shape changes as a mechanism of embryonic heart looping. Dev. Biol. 29:349–371, 1972.CrossRefPubMedGoogle Scholar
  16. 16.
    Manasek, F. J., R. R. Kulikowski, A. Nakamura, Q. Nguyenphuc, and J. W. Lacktis. Early heart development: a new model of cardiac morphogenesis. In: Growth of the Heart in Health and Disease, edited by R. Zak. New York: Raven Press, 1984, pp. 105–130.Google Scholar
  17. 17.
    Manasek, F. J., and R. G. Monroe. Early cardiac morphogenesis is independent of function. Dev. Biol. 27:584–588, 1972.CrossRefPubMedGoogle Scholar
  18. 18.
    Manner, J. Cardiac looping in the chick embryo: a morphological review with special reference to terminological and biomechanical aspects of the looping process. Anat. Rec. 259:248–262, 2000.CrossRefPubMedGoogle Scholar
  19. 19.
    Nakamura, A., and F. J. Manasek. An experimental study of the relation of cardiac jelly to the shape of the early chick embryonic heart. J. Embryol. Exp. Morph. 65:235–256, 1981.PubMedGoogle Scholar
  20. 20.
    Patten, B. M. The formation of the cardiac loop in the chick. Am. J. Anat. 30:373–397, 1922.CrossRefGoogle Scholar
  21. 21.
    Rodriguez, E. K., A. Hoger, and A. D. McCulloch. Stress-dependent finite growth in soft elastic tissues. J. Biomech. 27:455–467, 1994.CrossRefPubMedGoogle Scholar
  22. 22.
    Romanoff, A. L. The Avian Embryo: Structural and Functional Development. New York: Macmillan, 1960.Google Scholar
  23. 23.
    Shiraishi, I., T. Takamatsu, T. Minamikawa, and S. Fujita. 3-D observation of actin filaments during cardiac myofibrinogenesis in chick embryo using a confocal laser scanning microscope. Anat. Embryol. 185:401–408, 1992.CrossRefPubMedGoogle Scholar
  24. 24.
    Srivastava, D., and E. N. Olson. Knowing in your heart what's right. Trends Cell Biol. 7:447–453, 1997.CrossRefPubMedGoogle Scholar
  25. 25.
    Stalsberg, H., and R. L. DeHaan. The precardiac areas and formation of the tubular heart in the chick embryo. Dev. Biol. 19:128–159, 1969.CrossRefPubMedGoogle Scholar
  26. 26.
    Taber, L. A. Biomechanics of cardiovascular development. Ann. Rev. Biomed. Eng. 3:1–25, 2001.CrossRefGoogle Scholar
  27. 27.
    Taber, L. A. Biomechanics of growth, remodeling, and morphogenesis. Appl. Mech. Rev. 48:487–545, 1995.CrossRefGoogle Scholar
  28. 28.
    Taber, L. A. Biophysical mechanisms of cardiac looping. Int. J. Dev. Biol. 50:323–332, 2006.Google Scholar
  29. 29.
    Taber, L. A., H. Sun, E. B. Clark, and B. B. Keller. Epicardial strains in embryonic chick ventricle at stages 16 through 24. Circ. Res. 75:896–903, 1994.PubMedGoogle Scholar
  30. 30.
    Voronov, D. A., P. W. Alford, G. Xu, and L. A. Taber. The role of mechanical forces in dextral rotation during cardiac looping in the chick embryo. Dev. Biol. 272:339–350, 2004.CrossRefPubMedGoogle Scholar
  31. 31.
    Voronov, D. A., and L. A. Taber. Cardiac looping in experimental conditions: The effects of extra embryonic forces. Dev. Dyn. 224:413–421, 2002.CrossRefPubMedGoogle Scholar
  32. 32.
    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.CrossRefPubMedGoogle Scholar
  33. 33.
    Zamir, E. A., and L. A. Taber. Material properties and residual stress in the stage 12 chick heart during cardiac looping. J. Biomech. Eng. 126:823–830, 2004.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Ashok Ramasubramanian
    • 1
  • Kimberly S. Latacha
    • 1
  • Jessica M. Benjamin
    • 1
  • Dmitry A. Voronov
    • 1
    • 2
  • Arvind Ravi
    • 1
  • Larry A. Taber
    • 1
    • 3
  1. 1.Department of Biomedical EngineeringWashington UniversitySt. LouisUSA
  2. 2.Institute for Information Transmission ProblemsRussian Academy of SciencesMoscowRussia
  3. 3.Department of Biomedical EngineeringWashington UniversitySt. LouisUSA

Personalised recommendations