Skip to main content
SpringerLink
Log in

Normal Development and Morphology of the Right Ventricle: Clinical Relevance

  • Chapter
  • First Online:
The Right Ventricle in Health and Disease

Part of the book series: Respiratory Medicine ((RM))

  • 2072 Accesses

Abstract

In the four-chambered human heart each cavity has its own morphological characteristics. As expected, they show also functional differences related to this morphology. It was a long nursed belief that hemodynamic changes after birth were largely responsible for these morphological and functional differences. This was clinically important as in patients with congenital heart disease, e.g. the univentricular correction (so-called Fontan procedure) was believed to lead to myocardial remodelling of the non-systemic right ventricle (RV) into a ventricle that could sustain the systemic circulation. This view proved to be too optimistic. Nowadays we know that in development (1) the RV and left ventricle (LV) derive from a temporo-spatially different source of cardiomyocytes that acquire their own specific architecture and genetic profile, (2) that the modulating epicardial contribution is different, and (3) that the coronary vascular system and microvasculature between the RV and LV differ. Based on these developmental data there is clearly a case for specific morphological, functional and remodelling capacities of the RV that set it apart from the LV.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Bleasdale RA, Frenneaux MP. Prognostic importance of right ventricular dysfunction. Heart. 2002;88:323–4.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation. 2008;117:1717–31.

    Article  PubMed  Google Scholar 

  3. Dore A, Houde C, Chan KL, et al. Angiotensin receptor blockade and exercise capacity in adults with systemic right ventricles: a multicenter, randomized, placebo-controlled clinical trial. Circulation. 2005;112:2411–6.

    Article  PubMed  CAS  Google Scholar 

  4. Provencher S, Herve P, Jais X, et al. Deleterious effects of beta-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension. Gastroenterology. 2006; 130:120–6.

    Article  PubMed  CAS  Google Scholar 

  5. van der Bom T, Winter MM, Bouma BJ, et al. Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial. Circulation. 2013;127: 322–30.

    Article  PubMed  Google Scholar 

  6. Thum T, Borlak J. Gene expression in distinct regions of the heart. Lancet. 2000;355:979–83.

    Article  PubMed  CAS  Google Scholar 

  7. Gittenberger-de Groot AC, Sauer U, Bindl L, Babic R, Essed CE, Buhlmeyer K. Competition of coronary arteries and ventriculo-coronary arterial communications in pulmonary atresia with intact ventricular septum. Int J Cardiol. 1988;18:243–58.

    Article  PubMed  CAS  Google Scholar 

  8. Gittenberger-de Groot AC, Tennstedt C, Chaoui R, Lie-Venema H, Sauer U, Poelmann RE. Ventriculo coronary arterial communications (VCAC) and myocardial sinusoids in hearts with pulmonary artresia with intact ventricular septum: two different diseases. Prog Pediatr Cardiol. 2001;13:157–64.

    Article  Google Scholar 

  9. Daubeney PE, Delany DJ, Anderson RH, et al. Pulmonary atresia with intact ventricular septum: range of morphology in a population-based study. J Am Coll Cardiol. 2002;39:1670–9.

    Article  PubMed  Google Scholar 

  10. Umar S, de Visser YP, Steendijk P, et al. Allogenic stem cell therapy improves right ventricular function by improving lung pathology in rats with pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2009;297:H1606–16.

    Article  PubMed  CAS  Google Scholar 

  11. Castellani C, Padalino M, China P, et al. Bone-marrow-derived CXCR4-positive tissue-committed stem cell recruitment in human right ventricular remodeling. Hum Pathol. 2010;41: 1566–76.

    Article  PubMed  CAS  Google Scholar 

  12. van Mierop LH, Kutsche LM. Development of the ventricular septum of the heart. Heart Vessels. 1985;1:114–9.

    Article  PubMed  Google Scholar 

  13. Wenink ACG. Embryology of the ventricular septum. Separate origin of its components. Virchows Arch. 1981;390:71–9.

    Article  CAS  Google Scholar 

  14. Pexieder T. Development of the outflow tract of the embryonic heart. Birth Defects. 1978;14:29–68.

    PubMed  CAS  Google Scholar 

  15. Viragh S, Challice CE. Origin and differentiation of cardiac muscle cells in the mouse. J Ultrastruct Res. 1973;42:1–24.

    Article  PubMed  CAS  Google Scholar 

  16. De la Cruz MV, Gomez CS, Arteaga MM, Argüello C. Experimental study of the development of the truncus and the conus in the chick embryo. J Anat. 1977;123:661–86.

    PubMed  PubMed Central  Google Scholar 

  17. Mjaatvedt CH, Nakaoka T, Moreno-Rodriguez R, et al. The outflow tract of the heart is recruited from a novel heart-forming field. Dev Biol. 2001;238:97–109.

    Article  PubMed  CAS  Google Scholar 

  18. Waldo KL, Hutson MR, Ward CC, et al. Secondary heart field contributes myocardium and smooth muscle to the arterial pole of the developing heart. Dev Biol. 2005;281:78–90.

    Article  PubMed  CAS  Google Scholar 

  19. Cai CL, Liang X, Shi Y, et al. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell. 2003;5: 877–89.

    Article  PubMed  CAS  Google Scholar 

  20. Abu-Issa R, Waldo K, Kirby ML. Heart fields: one, two or more? Dev Biol. 2004;272:281–5.

    Article  PubMed  CAS  Google Scholar 

  21. Meilhac SM, Esner M, Kelly RG, Nicolas JF, Buckingham ME. The clonal origin of myocardial cells in different regions of the embryonic mouse heart. Dev Cell. 2004;6:685–98.

    Article  PubMed  CAS  Google Scholar 

  22. Kelly RG. Building the right ventricle. Circ Res. 2007;100:943–5.

    Article  PubMed  CAS  Google Scholar 

  23. Bajolle F, Zaffran S, Kelly RG, et al. Rotation of the myocardial wall of the outflow tract is implicated in the normal positioning of the great arteries. Circ Res. 2006;98:421–8.

    Article  PubMed  CAS  Google Scholar 

  24. Douglas YL, Jongbloed MR, DeRuiter MC, Gittenberger-de Groot AC. Normal and abnormal development of pulmonary veins: state of the art and correlation with clinical entities. Int J Cardiol. 2010;147:13–24.

    Article  PubMed  Google Scholar 

  25. Lescroart F, Mohun T, Meilhac SM, Bennett M, Buckingham M. Lineage tree for the venous pole of the heart: clonal analysis clarifies controversial genealogy based on genetic tracing. Circ Res. 2012;111:1313–22.

    Article  PubMed  CAS  Google Scholar 

  26. Pexieder T. Cell death in the morphogenesis and teratogenesis of the heart. Adv Anat Embryol Cell Biol. 1975;51:1–99.

    Google Scholar 

  27. Bajolle F, Zaffran S, Meilhac SM, et al. Myocardium at the base of the aorta and pulmonary trunk is prefigured in the outflow tract of the heart and in subdomains of the second heart field. Dev Biol. 2008;313:25–34.

    Article  PubMed  CAS  Google Scholar 

  28. Scherptong RW, Jongbloed MR, Wisse LJ, et al. Morphogenesis of outflow tract rotation during cardiac development: the pulmonary push concept. Dev Dyn. 2012;241:1413–22.

    Article  PubMed  Google Scholar 

  29. Kruithof BP, Kruithof-de Julio M, Poelmann RE, Gittenberger-de-Groot AC, Gaussin V, Goumans MJ. Early myocardial trabeculation and differential remodeling of the left and right atrioventricular myocardium; implications for cardiac valve formation and a role for TGFbeta2. Int J Dev Biol. 2013; in press.

    Google Scholar 

  30. Sedmera D, Pexieder T, Rychterova V, Hu N, Clark EB. Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions. Anat Rec. 1999;254:238–52.

    Article  PubMed  CAS  Google Scholar 

  31. Wenink ACG, Gittenberger-de Groot AC. Left and right ventricular trabecular patterns. Consequence of ventricular septation and valve development. Br Heart J. 1982;48:462–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Gittenberger-de Groot AC, Winter EM, Bartelings MM, Goumans MJ, DeRuiter MC, Poelmann RE. The arterial and cardiac epicardium in development, disease and repair. Differentiation. 2012;84:41–53.

    Article  PubMed  CAS  Google Scholar 

  33. Vrancken Peeters M-PFM, Mentink MMT, Poelmann RE, Gittenberger-de Groot AC. Cytokeratins as a marker for epicardial formation in the quail embryo. Anat Embryol. 1995;191:503–8.

    PubMed  CAS  Google Scholar 

  34. Perez-Pomares JM, Pompa JL. Signaling during epicardium and coronary vessel development. Circ Res. 2011;109:1429–42.

    Article  PubMed  CAS  Google Scholar 

  35. Limana F, Capogrossi MC, Germani A. The epicardium in cardiac repair: from the stem cell view. Pharmacol Ther. 2011;129:82–96.

    Article  PubMed  CAS  Google Scholar 

  36. Smart N, Dube KN, Riley PR. Epicardial progenitor cells in cardiac regeneration and neovascularisation. Vascul Pharmacol. 2013;58:164–73.

    Article  PubMed  CAS  Google Scholar 

  37. Bax NA, Van Oorschot AA, Maas S, et al. In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFbeta-signaling and WT1. Basic Res Cardiol. 2011;106:829–47.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Acharya A, Baek ST, Huang G, et al. The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors. Development. 2012;139:2139–49.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  39. Gittenberger-de Groot AC, Vrancken Peeters MP, Bergwerff M, Mentink MM, Poelmann RE. Epicardial outgrowth inhibition leads to compensatory mesothelial outflow tract collar and abnormal cardiac septation and coronary formation. Circ Res. 2000;87:969–71.

    Article  PubMed  CAS  Google Scholar 

  40. Bogers AJJC, Gittenberger-de Groot AC, Poelmann RE, Péault BM, Huysmans HA. Development of the origin of the coronary arteries, a matter of ingrowth or outgrowth? Anat Embryol. 1989;180:437–41.

    Article  PubMed  CAS  Google Scholar 

  41. Eralp I, Lie-Venema H, DeRuiter MC, et al. Coronary artery and orifice development is associated with proper timing of epicardial outgrowth and correlated Fas ligand associated apoptosis patterns. Circ Res. 2005;96:526–34.

    Article  PubMed  CAS  Google Scholar 

  42. Tian X, Hu T, He L, et al. Peritruncal coronary endothelial cells contribute to proximal coronary artery stems and their aortic orifices in the mouse heart. PLoS One. 2013;8:e80857.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lie-Venema H, Gittenberger-de Groot AC, van Empel LJP, et al. Ets-1 and Ets-2 transcription factors are essential for normal coronary and myocardial development in chicken embryos. Circ Res. 2003;92:749–56.

    Article  PubMed  CAS  Google Scholar 

  44. Sauer U, Gittenberger-de Groot AC, Geishauser M, Babic R, Buhlmeyer K. Coronary arteries in the hypoplastic left heart syndrome. Circulation. 1989;80:168–76.

    Google Scholar 

  45. Oosthoek PW, Moorman AFM, Sauer U, Gittenberger-de Groot AC. Capillary distribution in the ventricles of hearts with pulmonary atresia and intact ventricular septum. Circulation. 1995;91:1790–7.

    Article  PubMed  CAS  Google Scholar 

  46. Sauer U, Bindl L, Pilossoff V, et al. Pulmonary atresia with intact ventricular septum and right ventricle coronary artery fistulae: selection of patients for surgery. In: Doyle EF, Engler ME, Gersony WM, Rashlund WJ, Talmer NS, editors. Pediatric cardiology. New York: Springer; 1986. p. 566–78.

    Chapter  Google Scholar 

  47. Hokken RB, Bartelings MM, Bogers AJJC, Gittenberger-de Groot AC. Morphology of the pulmonary and aortic roots with regard to the pulmonary autograft procedure. J Thorac Cardiovasc Surg. 1997;113:453–61.

    Article  PubMed  CAS  Google Scholar 

  48. Bartelings MM, Gittenberger-de Groot AC. The arterial orifice level in the early human embryo. Anat Embryol. 1988;177:537–42.

    Article  PubMed  CAS  Google Scholar 

  49. Lalezari S, Hazekamp MG, Bartelings MM, Schoof PH, Gittenberger-de Groot AC. Pulmonary artery remodeling in transposition of the great arteries: relevance for neoaortic root dilatation. J Thorac Cardiovasc Surg. 2003;126:1053–60.

    Article  PubMed  Google Scholar 

  50. Torrent-Guasp F, Kocica MJ, Corno AF, et al. Towards new understanding of the heart structure and function. Eur J Cardiothorac Surg. 2005;27:191–201.

    Article  PubMed  Google Scholar 

  51. Meilhac SM, Esner M, Kerszberg M, Moss JE, Buckingham ME. Oriented clonal cell growth in the developing mouse myocardium underlies cardiac morphogenesis. J Cell Biol. 2004;164: 97–109.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  52. Poelmann RE, Mikawa T, Gittenberger-de Groot AC. Neural crest cells in outflow tract septation of the embryonic chicken heart: differentiation and apoptosis. Dev Dyn. 1998;212:373–84.

    Article  PubMed  CAS  Google Scholar 

  53. van den Hoff MJ, Moorman AF, Ruijter JM, et al. Myocardialization of the cardiac outflow tract. Dev Biol. 1999;212:477–90.

    Article  PubMed  Google Scholar 

  54. Waldo K, Miyagawa-Tomita S, Kumiski D, Kirby ML. Cardiac neural crest cells provide new insight into septation of the cardiac outflow tract: aortic sac to ventricular septal closure. Dev Biol. 1998;196:129–44.

    Article  PubMed  CAS  Google Scholar 

  55. Kirby ML, Gale TF, Stewart DE. Neural crest cells contribute to normal aorticopulmonary septation. Science. 1983;220:1059–61.

    Article  PubMed  CAS  Google Scholar 

  56. Gittenberger-de Groot AC, Bartelings MM, DeRuiter MC, Poelmann RE. Basics of cardiac development for the understanding of congenital heart malformations. Pediatr Res. 2005;57: 169–76.

    Article  PubMed  Google Scholar 

  57. Wenink ACG, Oppenheimer-Dekker A, Moulaert AJ. Muscular ventricular septal defects: a reappraisal of the anatomy. Am J Cardiol. 1979;43:259–64.

    Article  PubMed  CAS  Google Scholar 

  58. Lamers WH, Wessels A, Verbeek FJ, et al. New findings concerning ventricular septation in the human heart. Implications for maldevelopment. Circulation. 1992;86:1194–205.

    Article  PubMed  CAS  Google Scholar 

  59. Moorman AFM, Christoffels VM. Cardiac chamber formation: development, genes and evolution. Physiol Rev. 2003;83:1223–67.

    PubMed  CAS  Google Scholar 

  60. Voelkel NF, Natarajan R, Drake JI, Bogaard HJ. Right ventricle in pulmonary hypertension. Compr Physiol. 2011;1:525–40.

    PubMed  Google Scholar 

  61. Bogaard HJ, Natarajan R, Mizuno S, et al. Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med. 2010;182:652–60.

    Article  PubMed  CAS  Google Scholar 

  62. Borgdorff MA, Bartelds B, Dickinson MG, Steendijk P, Berger RM. A cornerstone of heart failure treatment is not effective in experimental right ventricular failure. Int J Cardiol. 2013;169:183–9.

    Article  PubMed  Google Scholar 

  63. Winter EM, Grauss RW, Hogers B, et al. Preservation of left ventricular function and attenuation of remodeling after transplantation of human epicardium-derived cells into the infarcted mouse heart. Circulation. 2007;116:917–27.

    Article  PubMed  CAS  Google Scholar 

  64. Winter EM, Van Oorschot AA, Hogers B, et al. A new direction for cardiac regeneration therapy: application of synergistically acting epicardium-derived cells and cardiomyocyte progenitor cells. Circ Heart Fail. 2009;2:643–53.

    Article  PubMed  Google Scholar 

  65. Zhou B, Pu WT. Epicardial epithelial-to-mesenchymal transition in injured heart. J Cell Mol Med. 2011;15:2781–3.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  66. Gittenberger-de-Groot AC, Winter EM, Poelmann RE. Epicardium-derived cells (EPDCs) in development, cardiac disease and repair of ischemia. J Cell Mol Med. 2010;14:1056–60.

    PubMed  Google Scholar 

  67. Smart N, Riley PR. The epicardium as a candidate for heart regeneration. Future Cardiol. 2012;8:53–69.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  68. Jongbloed MR, Vicente SR, Hahurij ND, et al. Normal and abnormal development of the cardiac conduction system; implications for conduction and rhythm disorders in the child and adult. Differentiation. 2012;84:131–48.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully thank Ron Slagter, Bert Wisse en Judith den Boeft for their help in preparing the figures.

Author information

Authors and Affiliations

  1. Depatment of Anatomy & Embryology, Cardiology, Leiden University Medical Center, Einthovenweg 20, Leiden, 2300 RL, The Netherlands

    Adriana L. Gittenberger-de Groot Ph.D. & Monique R. M. Jongbloed M.D., Ph.D.

  2. Department of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden, 2300 RL, The Netherlands

    Robert E. Poelmann Ph.D.

  3. Department of Pulmonary Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, 1007 MB, The Netherlands

    Harm Jan Bogaard M.D., Ph.D.

Authors
  1. Adriana L. Gittenberger-de Groot Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert E. Poelmann Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rebecca Vicente-Steijn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Margot M. Bartelings
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Harm Jan Bogaard M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Monique R. M. Jongbloed M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adriana L. Gittenberger-de Groot Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

    Norbert F. Voelkel

  2. Pediatric Heart Center, Justus-Liebig University, Giessen, Germany

    Dietmar Schranz

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Video 1.1

Animated three-dimensional reconstruction demonstrating the asymmetric contribution of Nkx2.5 expressing cells (bright yellow) within the heart and anterior heart field at embryonic day (ED) 12.5. This column is rendered transparent during part of the animation to demonstrate its relation to the aorta (red) and pulmonary trunk (dark blue). The outflow tract and right ventricle are depicted in light-yellow, and the left ventricle is depicted in grey. Additional colour coding: Light blue: endocardial cushion tissue. Movie published in [28], and reproduced with permission. (AVI 33624 kb)

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Groot, A.L.Gd., Poelmann, R.E., Vicente-Steijn, R., Bartelings, M.M., Bogaard, H.J., Jongbloed, M.R.M. (2015). Normal Development and Morphology of the Right Ventricle: Clinical Relevance. In: Voelkel, N., Schranz, D. (eds) The Right Ventricle in Health and Disease. Respiratory Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1065-6_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1065-6_1

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1064-9

  • Online ISBN: 978-1-4939-1065-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation