The Neonatal Transition of the Right Ventricle

Chapter
Part of the Respiratory Medicine book series (RM)

Abstract

The pulmonary circulation undergoes a dramatic transition at birth, which includes a marked fall in pulmonary vascular resistance (PVR) to accommodate an eight- to tenfold increase in pulmonary blood flow. Failure to achieve or sustain this normal drop in PVR leads to the syndrome of persistent pulmonary hypertension of the newborn (PPHN), which is characterized by profound hypoxemia due to extra-pulmonary shunt, poor cardiac output, and significant morbidity and mortality. The fetal myocardium must also adapt rapidly during the transition, and the right ventricle (RV) undergoes striking functional and structural changes after birth. The RV serves as the “systemic ventricle” in utero, as most of the RV output crosses the widely patent DA and provides 2/3 of combined ventricular output in the normal fetus. Increased systemic vascular resistance, the marked fall in PVR, and functional closure of the “fetal channels” account for the progressive decrease in RV wall thickness and increase in LV mass after birth. Unlike changes in the RV during the normal transition, RV hypertrophy persists in the setting of sustained elevations of PVR due to birth at altitude, PPHN, congenital heart disease, and other cardiopulmonary disorders. In addition to these striking physiologic changes, the neonatal transition of the RV is further characterized by remarkable cellular, molecular, and metabolic adaptations. The fetal heart grows and develops during normal intrauterine life at low oxygen tensions that would induce severe hypoxic stress during postnatal life, yet the fetus thrives and is well-prepared for the normal transition at birth. Insights into mechanisms underlying the normal metabolic and functional transition from fetal to neonatal life are not only important for better understanding of neonatal cardiopulmonary diseases, but will also provide insights into adaptive and maladaptive responses in the adult RV.

Keywords

Ischemia Carbohydrate Dopamine Lactate Pneumonia 

References

  1. 1.
    Rudolph AM. Fetal and neonatal pulmonary circulation. Annu Rev Physiol. 1979;41(1): 383–95.PubMedCrossRefGoogle Scholar
  2. 2.
    Gao Y, Raj JU. Regulation of the pulmonary circulation in the fetus and newborn. Physiol Rev. 2010;90(4):1291–335.PubMedCrossRefGoogle Scholar
  3. 3.
    Heymann MA, Soifer SJ. Control of fetal and neonatal pulmonary circulation. In: Weir EK, Reeves JT, editors. Pulmonary vascular physiology and pathophysiology. New York: Dekker; 1989. p. 33–50.Google Scholar
  4. 4.
    Levin DL, Heymann MA, Kitterman JA, Gregory GA, Phibbs RH, Rudolph AM. Persistent pulmonary hypertension of the newborn infant. J Pediatr. 1976;89(4):626–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Abman SH, Kinsella JP. Inhaled nitric oxide for persistent pulmonary hypertension of the newborn: the physiology matters! Pediatrics. 1995;96(6):1153–5.PubMedGoogle Scholar
  6. 6.
    Geggel RL, Reid LM. The structural basis of PPHN. Clin Perinatol. 1984;11(3):525–49.PubMedGoogle Scholar
  7. 7.
    Rudolph AM. The changes in the circulation after birth. Their importance in congenital heart disease. Circulation. 1970;41(2):343–59.PubMedCrossRefGoogle Scholar
  8. 8.
    Rudolph A. Congenital diseases of the heart. 3rd ed. San Francisco, CA: Wiley; 2011.Google Scholar
  9. 9.
    Patterson AJ, Zhang L. Hypoxia and fetal heart development. Curr Mol Med. 2010;10(7):653.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Cavasin MA, Demos-Davies K, Horn TR, Walker LA, Lemon DD, Birdsey N, et al. Selective class I histone deacetylase inhibition suppresses hypoxia-induced cardiopulmonary remodeling through an antiproliferative mechanism. Circ Res. 2012;110(5):739–48.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Archer SL, Marsboom G, Kim GH, Zhang HJ, Toth PT, Svensson EC, et al. Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: a basis for excessive cell proliferation and a new therapeutic target. Circulation. 2010;121(24):2661–71.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Friedman WF. The intrinsic physiologic properties of the developing heart. Prog Cardiovasc Dis. 1972;15(1):87–111.PubMedCrossRefGoogle Scholar
  13. 13.
    Fisher DJ, Heymann MA, Rudolph AM. Myocardial oxygen and carbohydrate consumption in fetal lambs in utero and in adult sheep. Am J Physiol. 1980;238(3):H399–405.PubMedGoogle Scholar
  14. 14.
    Taegtmeyer H, Sen S, Vela D. Return to the fetal gene program. Ann N Y Acad Sci. 2010;1188(1):191–8.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Ascuitto RJ, Ross-Ascuitto NT. Substrate metabolism in the developing heart. Semin Perinatol. 1996;20(6):542–63.PubMedCrossRefGoogle Scholar
  16. 16.
    Compernolle V, Brusselmans K, Franco D, Moorman A, Dewerchin M, Collen D, et al. Cardia bifida, defective heart development and abnormal neural crest migration in embryos lacking hypoxia-inducible factor-1alpha. Cardiovasc Res. 2003;60(3):569–79.PubMedCrossRefGoogle Scholar
  17. 17.
    Sugishita Y, Leifer DW, Agani F, Watanabe M, Fisher SA. Hypoxia-responsive signaling regulates the apoptosis-dependent remodeling of the embryonic avian cardiac outflow tract. Dev Biol. 2004;273(2):285–96.PubMedCrossRefGoogle Scholar
  18. 18.
    Fisher SA, Burggren WW. Role of hypoxia in the evolution and development of the cardiovascular system. Antioxid Redox Signal. 2007;9(9):1339–52.PubMedCrossRefGoogle Scholar
  19. 19.
    Hue L, Taegtmeyer H. The Randle cycle revisited: a new head for an old hat. Am J Physiol Endocrinol Metab. 2009;297(3):E578–91.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963;1(7285): 785–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Altin SE, Schulze PC. Metabolism of the right ventricle and the response to hypertrophy and failure. Prog Cardiovasc Dis. 2012;55(2):229–33.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Razeghi P, Young ME, Alcorn JL, Moravec CS, Frazier OH, Taegtmeyer H. Metabolic gene expression in fetal and failing human heart. Circulation. 2001;104(24):2923–31.PubMedCrossRefGoogle Scholar
  23. 23.
    Kates AM, Herrero P, Dence C, Soto P, Srinivasan M, Delano DG, et al. Impact of aging on substrate metabolism by the human heart. J Am Coll Cardiol. 2003;41(2):293–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Can MM, Kaymaz C, Tanboga IH, Tokgoz HC, Canpolat N, Turkyilmaz E, et al. Increased right ventricular glucose metabolism in patients with pulmonary arterial hypertension. Clin Nucl Med. 2011;36(9):743–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Rudolph AM. High pulmonary vascular resistance after birth: I. Pathophysiologic considerations and etiologic classification. Clin Pediatr. 1980;19(9):585–90.CrossRefGoogle Scholar
  26. 26.
    Fisher DJ, Heymann MA, Rudolph AM. Regional myocardial blood flow and oxygen delivery in fetal, newborn, and adult sheep. Am J Physiol. 1982;243(5):H729–31.PubMedGoogle Scholar
  27. 27.
    Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet. 1986;1(8489):1077–81.PubMedCrossRefGoogle Scholar
  28. 28.
    Lewandowski AJ, Bradlow WM, Augustine D, Davis EF, Francis J, Singhal A, et al. Right ventricular systolic dysfunction in young adults born preterm. Circulation. 2013;128(7):713–20.PubMedCrossRefGoogle Scholar
  29. 29.
    Lewandowski AJ, Augustine D, Lamata P, Davis EF, Lazdam M, Francis J, et al. Preterm heart in adult life: cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function. Circulation. 2013;127(2):197–206.PubMedCrossRefGoogle Scholar
  30. 30.
    Rudolph AM. Myocardial growth before and after birth: clinical implications. Acta Paediatr. 2007;89(2):129–33.CrossRefGoogle Scholar
  31. 31.
    St John Sutton MG, Raichlen JS, Reichek N, Huff DS. Quantitative assessment of right and left ventricular growth in the human fetal heart: a pathoanatomic study. Circulation. 1984; 70(6):935–41.PubMedCrossRefGoogle Scholar
  32. 32.
    Thornburg KL, Morton MJ. Filling and arterial pressures as determinants of left ventricular stroke volume in fetal lambs. Am J Physiol. 1986;251(5 Pt 2):H961–8.PubMedGoogle Scholar
  33. 33.
    Gilbert RD. Control of fetal cardiac output during changes in blood volume. Am J Physiol. 1980;238(1):H80–6.PubMedGoogle Scholar
  34. 34.
    Romero T, Covell J, Friedman WF. A comparison of pressure-volume relations of the fetal, newborn, and adult heart. Am J Physiol. 1972;222(5):1285–90.PubMedGoogle Scholar
  35. 35.
    Rychik J. Fetal cardiovascular physiology. Pediatr Cardiol. 2004;25(3):201–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Reller MD, Morton MJ, Reid DL, Thornburg KL. Fetal lamb ventricles respond differently to filling and arterial pressures and to in utero ventilation. Pediatr Res. 1987;22(6):621–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Thornburg KL, Morton MJ. Filling and arterial pressures as determinants of RV stroke volume in the sheep fetus. Am J Physiol. 1983;244(5):H656–63.PubMedGoogle Scholar
  38. 38.
    Levin DL, Hyman AI, Heymann MA, Rudolph AM. Fetal hypertension and the development of increased pulmonary vascular smooth muscle: a possible mechanism for persistent pulmonary hypertension of the newborn infant. J Pediatr. 1978;92(2):265–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Abman SH, Shanley PF, Accurso FJ. Failure of postnatal adaptation of the pulmonary circulation after chronic intrauterine pulmonary hypertension in fetal lambs. J Clin Invest. 1989; 83(6):1849–58.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Mahony L, Jones LR. Developmental changes in cardiac sarcoplasmic reticulum in sheep. J Biol Chem. 1986;261(32):15257–65.PubMedGoogle Scholar
  41. 41.
    Rasanen J, Wood DC, Debbs RH, Cohen J, Weiner S, Huhta JC. Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy: a randomized study. Circulation. 1998;97(3):257–62.PubMedCrossRefGoogle Scholar
  42. 42.
    Seed M, van Amerom JFP, Yoo S-J, Nafisi Al B, Grosse-Wortmann L, Jaeggi E, et al. Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study. J Cardiovasc Magn Reson. 2012;14:79.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Grant DA, Hollander E, Skuza EM, Fauchère JC. Interactions between the right ventricle and pulmonary vasculature in the fetus. J Appl Physiol. 1999;87(5):1637–43.PubMedGoogle Scholar
  44. 44.
    Abman SH, Chatfield BA, Hall SL, McMurtry IF. Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth. Am J Physiol. 1990;259(6 Pt 2):H1921–7.PubMedGoogle Scholar
  45. 45.
    Joyce JJ, Dickson PI, Qi N, Noble JE, Raj JU, Baylen BG. Normal right and left ventricular mass development during early infancy. Am J Cardiol. 2004;93(6):797–801.PubMedCrossRefGoogle Scholar
  46. 46.
    Smolich JJ, Walker AM, Campbell GR, Adamson TM. Left and right ventricular myocardial morphometry in fetal, neonatal, and adult sheep. Am J Physiol. 1989;257(1 Pt 2):H1–9.PubMedGoogle Scholar
  47. 47.
    Anversa P, Olivetti G, Loud AV. Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. I. Hypertrophy, hyperplasia, and binucleation of myocytes. Circ Res. 1980;46(4):495–502.PubMedCrossRefGoogle Scholar
  48. 48.
    Olivetti G, Anversa P, Loud AV. Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. II. Tissue composition, capillary growth, and sarcoplasmic alterations. Circ Res. 1980;46(4):503–12.PubMedCrossRefGoogle Scholar
  49. 49.
    Klopfenstein HS, Rudolph AM. Postnatal changes in the circulation and responses to volume loading in sheep. Circ Res. 1978;42(6):839–45.PubMedCrossRefGoogle Scholar
  50. 50.
    Haworth SG, Hislop AA. Effect of hypoxia on adaptation of the pulmonary circulation to extra-uterine life in the pig. Cardiovasc Res. 1982;16(6):293–303.PubMedCrossRefGoogle Scholar
  51. 51.
    Hislop A, Reid L. Intra-pulmonary arterial development during fetal life-branching pattern and structure. J Anat. 1972;113(Pt 1):35.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Chin KM, Coghlan G. Characterizing the right ventricle: advancing our knowledge. Am J Cardiol. 2012;110(6 Suppl):3S–8S.PubMedCrossRefGoogle Scholar
  53. 53.
    Kimball TR, Daniels SR, Khoury P, Meyer RA. Age-related variation in contractility estimate in patients less than or equal to 20 years of age. Am J Cardiol. 1991;68(13):1383–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Teitel DF, Sidi D, Chin T, Brett C, Heymann MA, Rudolph AM. Developmental changes in myocardial contractile reserve in the lamb. Pediatr Res. 1985;19(9):948–55.PubMedCrossRefGoogle Scholar
  55. 55.
    Danhaive O, Margossian R, Geva T, Kourembanas S. Pulmonary hypertension and right ventricular dysfunction in growth-restricted, extremely low birth weight neonates. J Perinatol. 2005;25(7):495–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Koestenberger M, Nagel B, Ravekes W, Urlesberger B, Raith W, Avian A, et al. Systolic right ventricular function in preterm and term neonates: reference values of the tricuspid annular plane systolic excursion (TAPSE) in 258 patients and calculation of Z-score values. Neonatology. 2011;100(1):85–92.PubMedCrossRefGoogle Scholar
  57. 57.
    Kinsella JP, Neish SR, Shaffer E, Abman SH. Low dose inhalational nitric oxide therapy in PPHN. Lancet. 1992;340:819–20.PubMedCrossRefGoogle Scholar
  58. 58.
    Roberts JD, Polaner DM, Lang P, Zapol WM. Inhaled NO in PPHN. Lancet. 1992;340:818–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of PediatricsUniversity of Colorado School of MedicineAuroraUSA
  2. 2.Department of PediatricsUniversity of ColoradoDenverUSA

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