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The Normal Fetal and Neonatal Pulmonary Circulation

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Abstract

In utero, the pulmonary circulation is characterized by high pulmonary vascular resistance (PVR) and low pulmonary blood flow, as the fetal lung receives less than 8% of combined ventricular output. At birth, the pulmonary circulation must suddenly undergo a striking vasodilation to allow for an eightfold to tenfold rise in blood flow for the lung to assume its postnatal role in gas exchange. This acute change in pulmonary vascular tone and reactivity is followed by progressive vascular growth, remodeling, and structural adaptations, as the lung circulation continues to grow and mature over time in response to postnatal stimuli. Normal lung vascular development is not only critical for successful adaptation at birth, but ongoing growth and remodeling remains essential throughout postnatal life. The ability of the lung to successfully achieve normal gas exchange requires the growth and maintenance of an intricate system of airways and vessels, including the establishment of a thin yet vast blood–gas interface. Insights into basic mechanisms that regulate lung growth and maturation continue to provide new understanding of lung diseases and their treatment, in newborns and adults alike. Vascular growth in the lung is not only important regarding the risk for pulmonary hypertension, but normal vascular growth and structure are absolutely necessary for establishing sufficient surface area for gas exchange. Developmental abnormalities of the pulmonary circulation contribute to the pathological and pathophysiological processes of diverse diseases, including persistent pulmonary hypertension of the newborn, lung hypoplasia, congenital diaphragmatic hernia, and congenital heart disease. This chapter provides a brief overview of structural and functional changes in the pulmonary circulation that contribute to PVR during fetal life and mechanisms that contribute to the dramatic changes in vascular tone at birth in the normal newborn.

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References

  1. Burri PH (1999) Lung development and pulmonary angiogenesis. In: Gaultier C, Bourbon JR, Post M (eds) Lung development. Oxford University Press, New York, pp 122–151

    Google Scholar 

  2. deMello DE, Reid LM (2002) Prenatal and postnatal development of the pulmonary circulation. In: Haddad CG, Abman SH, Chernick VC (eds) Basic mechanisms of pediatric respiratory disease. Decker, Hamilton, pp 77–101

    Google Scholar 

  3. Hislop AA (2002) Airway and blood vessel interaction during lung development. J Anat 201:325–334

    Article  PubMed  Google Scholar 

  4. deMello DE, Reid LM (2002) Embryonic and early fetal development of human lung vasculature and its functional implications. Pediatr Dev Pathol 3:439–449

    Article  Google Scholar 

  5. Hall SM, Hislop AA, Pierce CM, Haworth SG (2000) Prenatal ­origins of human intrapulmonary arteries: formation and smooth muscle maturation. Am J Respir Cell Mol Biol 23:194–203

    PubMed  CAS  Google Scholar 

  6. DeRuiter MC, Gittenberger Groot AC, Rammos S, Poelmann RE (1989) The special status of the pulmonary arch artery in the branchial arch system of the rat. Anat Embryol 179:319–325

    Article  CAS  Google Scholar 

  7. deMello DE, Sawyer D, Galvin N, Reid LM (1997) Early fetal development of lung vasculature. Am J Respir Cell Mol Biol 16:568–581

    PubMed  CAS  Google Scholar 

  8. Chang C (1931) On the origins of the pulmonary vein. Anat Rec 50:1–8

    Article  Google Scholar 

  9. Fisher KA, Summer RS (2006) Stem and progenitor cells in the formation of the pulmonary vasculature. Curr Top Dev Biol 74:117–131

    Article  PubMed  CAS  Google Scholar 

  10. Shachtner SK, Wang Y, Baldwin HS (2000) Qualitative and quantitative analysis of embryonic pulmonary vessel formation. Am J Respir Cell Mol Biol 22:157–165

    Google Scholar 

  11. Gebb SA, Shannon JM (2000) Tissue interactions mediate early events in pulmonary vasculogenesis. Dev Dyn 217:159–169

    Article  PubMed  CAS  Google Scholar 

  12. Maeda S, Suzuki S, Suzuki T et al (2002) Analysis of intrapulmonary vessels and epithelial–endothelial interactions in the human developing lung. Lab Invest 82:293–301

    PubMed  Google Scholar 

  13. Parera MC, Van Dooren M, van Kempen M et al (2005) Distal angiogenesis: a new concept for lung vasculogenesis. Am J Physiol Lung 288:L141–L146

    Article  CAS  Google Scholar 

  14. Shannon JM, Deterding RM (1997) Epithelial–mesenchymal ­interactions in lung development. In: McDonald JA (ed) Lung growth and development. Dekker, New York, pp 81–118

    Google Scholar 

  15. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–672

    Article  PubMed  CAS  Google Scholar 

  16. Flamme I, Breier G, Risau W (1995) VEGF and VEGF receptor 2 are expressed during vasculogenesis and vascular differentiation in the quail embryo. Dev Biol 169:699–712

    Article  PubMed  CAS  Google Scholar 

  17. Millauer B, Wizigmann-Voos S, Schnürch H et al (1993) High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72:835–846

    Article  PubMed  CAS  Google Scholar 

  18. Akeson AL, Greenberg JM, Cameron JE et al (2003) Temporal and spatial regulation of VEGF-A controls vascular patterning in the embryonic lung. Dev Dyn 264:443–455

    CAS  Google Scholar 

  19. Terman BI, Dougher-Vermazen M, Carrion ME et al (1992) Identification of the KDR tyrosine kinase as a receptor for VEGF. Biochem Biophys Res Commun 187:1579–1586

    Article  PubMed  CAS  Google Scholar 

  20. Djonov V, Schmid M, Tschanz SA, Burri PH (2000) Intussusceptive angiogenesis: its role in embryonic vascular network formation. Circ Res 86:286–292

    PubMed  CAS  Google Scholar 

  21. Patan S, Alvarez MJ, Schittny JC, Burri PH (1992) Intussusceptive microvascular growth: a common alternative to capillary sprouting. Arch Histol Cytol 55:65–75

    Article  PubMed  Google Scholar 

  22. Gebb SA, Jones PL (2003) Hypoxia and lung branching morphogenesis. Adv Exp Med Biol 543:117–125

    PubMed  CAS  Google Scholar 

  23. Kotch LE, Iyer NV, Laughner E, Semenza GL (1999) Defective vascularization of HIF-1α null embryos is not associated with VEGF deficiency, but with mesenchymal cell death. Dev Biol 209:254–267

    Article  PubMed  CAS  Google Scholar 

  24. Davies PF (1995) Flow-mediated endothelial mechanotransduction. Physiol Rev 75:519–560

    PubMed  CAS  Google Scholar 

  25. Topper JN, Gimbrone MA Jr (1999) Blood flow and vascular gene expression fluid shear stress as a modulator of endothelial phenotype. Mol Med Today 5:40–46

    Article  PubMed  CAS  Google Scholar 

  26. Grover TR, Parker TA, Balasubramaniam V, Markham NE, Abman SH (2005) Pulmonary hypertension impairs alveolarization and lung growth in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 288:L648–L654

    Article  PubMed  CAS  Google Scholar 

  27. Grover TR, Parker TA, Markham NE, Abman SH et al (2005) rhVEGF treatment preserves pulmonary vasoreactivity and structure in an experimental model of pulmonary hypertension in fetal sheep. Am J Physiol Lung Cell Mol Physiol 289:L315–L321

    Article  PubMed  CAS  Google Scholar 

  28. Heymann MA, Soifer SJ (1989) Control of fetal and neonatal pulmonary circulation. In: Weir EK, Reeves JT (eds) Pulmonary vascular physiology and pathophysiology. Dekker, New York, pp 33–50

    Google Scholar 

  29. Rasanen J, Wood DC, Debbs RH, Cohen J, Weiner S, Huhta JC (1998) Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy. A randomized study. Circulation 97:257–262

    PubMed  CAS  Google Scholar 

  30. Abman SH, Chatfield BA, Hall SL, McMurtry IF (1990) Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth. Am J Physiol 259:H1921–H1927

    PubMed  CAS  Google Scholar 

  31. Cassin S (1987) Role of prostaglandins, thromboxanes and leukotrienes in the control of the pulmonary circulation in the fetus and newborn. Semin Perinatol 11:53–63

    PubMed  CAS  Google Scholar 

  32. Cornfield DN, Chatfield BA, McQueston JA, McMurtry IF, Abman SH (1992) Effects of birth-related stimuli on l-arginine-dependent pulmonary vasodilation in the ovine fetus. Am J Physiol 262:H1474–H1481

    PubMed  CAS  Google Scholar 

  33. Cornfield DN, Reeve HL, Tolarova S, Weir EK, Archer SL (1996) Oxygen causes fetal pulmonary vasodilation through activation of a calcium-dependent potassium channel. Proc Natl Acad Sci U S A 93:8089–8094

    Article  PubMed  CAS  Google Scholar 

  34. Velvis H, Moore P, Heymann MA (1991) Prostaglandin inhibition prevents the fall in pulmonary vascular resistance as the result of rhythmic distension of the lungs in fetal lambs. Pediatr Res 30:62–67

    PubMed  CAS  Google Scholar 

  35. Ivy DD, Kinsella JP, Abman SH (1994) Physiologic characterization of endothelin A and B receptor activity in the ovine fetal lung. J Clin Invest 93:2141–2148

    Article  PubMed  CAS  Google Scholar 

  36. Rudolph AM, Heymann MA, Lewis AB (1977) Physiology and pharmacology of the pulmonary circulation in the fetus and newborn. In: Hodson W (ed) Development of the lung. Dekker, New York, pp 497–523

    Google Scholar 

  37. Morin FC, Egan EA, Ferguson W, Lundgren CEG (1988) Development of pulmonary vascular response to oxygen. Am J Physiol 254:H542–H546

    PubMed  Google Scholar 

  38. Abman SH, Chatfield BA, Rodman DM, Hall SL, McMurtry IF (1991) Maturation-related changes in endothelium-dependent relaxation of ovine pulmonary arteries. Am J Physiol 260:L280–L285

    PubMed  CAS  Google Scholar 

  39. North AJ, Star RA, Brannon TS et al (1994) NO synthase type I and type III gene expression are developmentally regulated in rat lung. Am J Physiol 266:L635–L641

    PubMed  CAS  Google Scholar 

  40. Halbower AC, Tuder RM, Franklin WA, Pollock JS, Forstermann U, Abman SH (1994) Maturation-related changes in endothelial NO synthase immunolocalization in the developing ovine lung. Am J Physiol 267:L585–L591

    PubMed  CAS  Google Scholar 

  41. Parker TA, Le Cras TD, Kinsella JP, Abman SH (2000) Devel­opmental changes in endothelial NO synthase expression in the ovine fetal lung. Am J Physiol 278:L202–L208

    CAS  Google Scholar 

  42. Kinsella JP, Ivy DD, Abman SH (1994) Ontogeny of NO activity and response to inhaled NO in the developing ovine pulmonary ­circulation. Am J Physiol 267:H1955–H1961

    PubMed  CAS  Google Scholar 

  43. Sherman TS, Chen Z, Yuhanna IS, Lau KS, Margraf LR, Shaul PW (1999) NO synthase isoform expression in the developing lung ­epithelium. Am J Phsyiol 276:L383–L390

    CAS  Google Scholar 

  44. Rairhig R, Ivy DD, Kinsella JP, Abman SH (1998) Inducible NOS inhibitors increase pulmonary vascular resistance in the late-gestation fetus. J Clin Invest 101:15–21

    Article  Google Scholar 

  45. Tzao C, Nickerson PA, Russell JA, Noble B, Steinhorn RM (2000) Heterogeneous distribution of type I NOS in pulmonary vasculature of ovine fetus. Histochem Cell Biol 114:421–430

    PubMed  CAS  Google Scholar 

  46. Rairigh RL, Storme L, Parker TA, Le Cras TD, Jakkula M, Abman SH (2000) Role of neuronal nitric oxide synthase in regulation of vascular and ductus arteriosus tone in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 278:L105–L110

    PubMed  CAS  Google Scholar 

  47. Rairigh RL, Parker TA, Ivy DD, Kinsella JP, Fan I, Abman SH (2001) Role of inducible nitric oxide synthase in the transition of the pulmonary circulation at birth. Circ Res 88:721–726

    Article  PubMed  CAS  Google Scholar 

  48. Abman SH, Kinsella JP, Parker TA, Storme L, Le Cras TD (1999) Physiologic roles of NO in the perinatal pulmonary circulation. In: Weir EK, Archer SL, Reeves JT (eds) Fetal and neonatal pulmonary circulation. Futura, New York, pp 239–260

    Google Scholar 

  49. Parker TA, Kinsella JP, Galan HL, Richter G, Abman SH (2000) Prolonged infusions of estradiol dilate the ovine fetal pulmonary circulation. Pediatr Res 47:89–96

    Article  PubMed  CAS  Google Scholar 

  50. Parker TA, Afshar S, Kinsella JP, Ivy DD, Shaul PW, Abman SH (2001) Effects of chronic estrogen receptor blockade on the pulmonary circulation in the late gestation ovine fetus. Am J Physiol Heart Circ Physiol 281:H1005–H1014

    PubMed  CAS  Google Scholar 

  51. MacRitchie AN, Jun SS, Chen Z et al (1997) Estrogen upregulates endothelial NO synthase gene expression in fetal pulmonary artery endothelium. Circ Res 81:355–362

    PubMed  CAS  Google Scholar 

  52. Grover TR, Parker TA, Zenge JP, Markham NE, Abman SH (2003) Intrauterine hypertension decreases lung VEGF expression and VEGF inhibition causes pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 284:L508–L517

    PubMed  CAS  Google Scholar 

  53. Hanson KA, Burns F, Rybalkin SD, Miller J, Beavo J, Clarke WR (1995) Developmental changes in lung cGMP phosphodiesterase-5 activity, protein and message. Am J Respir Crit Care Med 158:279–288

    Google Scholar 

  54. Cohen AH, Hanson K, Morris K et al (1996) Inhibition of cGMP-specific phosphodiesterase selectively vasodilates the pulmonary circulation in chronically hypoxic rats. J Clin Invest 97:172–179

    Article  PubMed  CAS  Google Scholar 

  55. Tzao C, Nickerson PA, Russell JA, Noble BK, Steinhorn RH (2003) Paracrine role of soluble guanylate cyclase and type III nitric oxide synthase in ovine fetal pulmonary circulation: a double labeling immunohistochemical study. Histochem Cell Biol 119:125–130

    PubMed  CAS  Google Scholar 

  56. Thusu KG, Morin FC 3rd, Russell JA, Steinhorn RH (1995) The cGMP phosphodiesterase inhibitor zaprinast enhances the effect of NO. Am J Respir Crit Care Med 152:1605–1610

    PubMed  CAS  Google Scholar 

  57. Ziegler JW, Ivy DD, Fox JJ, Kinsella JP, Clarke WR, Abman SH (1995) Dipyridamole, a cGMP phosphodiesterase inhibitor, causes pulmonary vasodilation in the ovine fetus. Am J Physiol 269:H473–H479

    PubMed  CAS  Google Scholar 

  58. Accurso FJ, Alpert B, Wilkening RB, Petersen RG, Meschia G (1986) Time-dependent response of fetal pulmonary blood flow to an increase in fetal oxygen tension. Respir Physiol 63:43–52

    Article  PubMed  CAS  Google Scholar 

  59. Abman SH, Accurso FJ (1989) Acute effects of partial compression of the ductus arteriosus on the fetal pulmonary circulation. Am J Physiol 257:H626–H634

    PubMed  CAS  Google Scholar 

  60. Abman SH, Accurso FJ (1991) Sustained fetal pulmonary ­vasodilation during prolonged infusion of atrial natriuretic factor and 8-bromo-guanosine monophosphate. Am J Physiol 260:H183–H192

    PubMed  CAS  Google Scholar 

  61. Meininger GA, Davis MJ (1992) Cellular mechanisms involved in the vascular myogenic response. Am J Physiol 263:H647–H659

    PubMed  CAS  Google Scholar 

  62. Kulik TJ, Evans JN, Gamble WJ (1988) Stretch-induced contraction in pulmonary arteries. Am J Physiol 255:H1191–H1198

    Google Scholar 

  63. Belik J, Stephens NL (1993) Developmental differences in vascular smooth muscle mechanics in pulmonary and systemic circulations. J Appl Physiol 74:682–687

    PubMed  CAS  Google Scholar 

  64. Storme L, Rairhig RL, Abman SH (1999) In vivo evidence for a myogenic response in the ovine fetal pulmonary circulation. Pediatr Res 45:425–431

    Article  PubMed  CAS  Google Scholar 

  65. Tourneux P, Chester M, Grover T, Abman SH (2008) Fasudil inhibits the myogenic response in the fetal pulmonary circulation. Am J Physiol Heart Circ Physiol 295:H1505–H1513

    Article  PubMed  CAS  Google Scholar 

  66. Leffler CW, Hessler JR, Green RS (1984) Mechanism of stimulation of pulmonary prostacyclin synthesis at birth. Prostaglandins 28:877–887

    Article  PubMed  CAS  Google Scholar 

  67. Leffler CW, Tyler TL, Cassin S (1978) Effect of indomethacin on pulmonary vascular response to ventilation of fetal goats. Am J Physiol 234:H346–H351

    PubMed  CAS  Google Scholar 

  68. Campbell WB, Harder DR (2001) Prologue: EDHF what is it? Am J Phyiol Heart Circ Physiol 280:H2413–H2416

    CAS  Google Scholar 

  69. Storme L, Rairigh RL, Parker TP, Cornfield DN, Kinsella JP, Abman SH (1999) Potassium channel blockade attenuates shear stress-induced pulmonary vasodilation in the ovine fetus. Am J Physiol 276:L220–L228

    PubMed  CAS  Google Scholar 

  70. Lin H, McGrath JJ (1988) Vasodilating effects of carbon monoxide. Drug Chem Toxicol 11:371–385

    Article  PubMed  CAS  Google Scholar 

  71. Kharitonov VG, Sharma VS, Pilz RB, Magde D, Koesling D (1995) Basis of guanylate cyclase activation of carbon monoxide. Proc Natl Acad Sci U S A 92:2568–2571

    Article  PubMed  CAS  Google Scholar 

  72. Grover TR, Rairigh RL, Zenge JP, Abman SH, Kinsella JP (2000) Inhaled carbon monoxide does not alter pulmonary vascular tone in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 278:L779–L784

    PubMed  CAS  Google Scholar 

  73. Soifer SJ, Loitz RD, Roman C, Heymann MA (1985) Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs. Am J Physiol 249:H570–H576

    PubMed  CAS  Google Scholar 

  74. Yanagisawa M, Kurihara H, Kimura S et al (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415

    Article  PubMed  CAS  Google Scholar 

  75. Boulanger C, Lüscher TF (1990) Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. J Clin Invest 85:587–590

    Article  PubMed  CAS  Google Scholar 

  76. Ivy DD, Abman SH (1999) Role of endothelin in perinatal pulmonary vasoregulation. In: Weir EK, Archer SL, Reeves JT (eds) Fetal and neonatal pulmonary circulation. Futura, New York, pp 279–302

    Google Scholar 

  77. Chatfield BA, McMurtry IF, Hall SL, Abman SH (1991) Hemodynamic effects of endothelin-1 on the ovine fetal pulmonary circulation. Am J Physiol 261:R182–R187

    PubMed  CAS  Google Scholar 

  78. Ivy DD, Kinsella JP, Abman SH (1996) Physiologic characterization of endothelin A and B receptor activity in the ovine fetal lung. J Clin Invest 93:2141–2148

    Article  Google Scholar 

  79. Ivy DD, Parker TA, Abman SH (2000) Prolonged endothelin B receptor blockade causes pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 279:L758–L765

    PubMed  CAS  Google Scholar 

  80. Coceani F, Kelsey L, Seidlitz E et al (1997) Carbon monoxide formation in the ductus arteriosus in the lamb: implications for the regulation of muscle tone. Br J Pharmacol 120:599–608

    Article  PubMed  CAS  Google Scholar 

  81. Tristani-Firouzi M, Reeve HL, Tolarova S, Weir EK, Archer SL (1996) Oxygen-induced constriction of rabbit ductus arteriosus occurs via inhibition of 4-aminopyridine, voltage-sensitive potassium channels. J Clin Invest 98:1959–1965

    Article  PubMed  CAS  Google Scholar 

  82. Reeve HL, Weir EK (1999) Regulation of ion channels in the ductus arteriosus. In: Weir EK, Archer SL, Reeves JT (eds) Fetal and neonatal pulmonary circulation. Futura, New York, pp 319–330

    Google Scholar 

  83. Archer SL, Huang JMC, Hampl V, Nelson DP, Shultz PJ, Weir EK (1994) NO and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci U S A 91:7583–7587

    Article  PubMed  CAS  Google Scholar 

  84. Rhodes MT, Porter VA, Saqueton CB, Herron JM, Resnik ER, Cornfield DN (2001) Pulmonary vascular response to normoxia and Kca channel activity is developmentally regulated. Am J Physiol Lung Cell Mol Physiol 280:L1250–L1257

    PubMed  CAS  Google Scholar 

  85. Tristani-Firouzi M, Martin EB, Tolarova S, Weir EK, Archer SL, Cornfield DN (1996) Ventilation-induced pulmonary vasodilation at birth is modulated by potassium channel activity. Am J Physiol 271:H2353–H2359

    PubMed  CAS  Google Scholar 

  86. Konduri GG, Mital S, Gervasio CT, Rotta AT, Forman K (1997) Purine nucleotides contribute to pulmonary vasodilation caused by birth-related stimuli in the ovine fetus. Am J Physiol 272:H2377–H2384

    PubMed  CAS  Google Scholar 

  87. Fagan KA, Fouty BW, Tyler RC et al (1999) The pulmonary circulation of mice with either homozygous or heterozygous disruption of endothelial NO synthase is hyper-responsive to chronic hypoxia. J Clin Invest 103:291–299

    Article  PubMed  CAS  Google Scholar 

  88. Steudel W, Scherrer-Crosbie M, Bloch KD et al (1998) Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of NOS III. J Clin Invest 101:2468–2477

    Article  PubMed  CAS  Google Scholar 

  89. Balasubramanium V, Maxey AM, Morgan DB, Markham NE, Abman SH (2006) Inhaled NO restores lung structure in eNOS-deficient mice recovering from neonatal hypoxia. Am J Physiol Lung Cell Mol Physiol 291:119–127

    PubMed  CAS  Google Scholar 

  90. Kinsella JP, McQueston JA, Rosenberg AA, Abman SH (1992) Hemodynamic effects of exogenous nitric oxide in ovine transitional pulmonary circulation. Am J Physiol 263:H875–H880

    PubMed  CAS  Google Scholar 

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Abman, S.H., Steinhorn, R.H. (2011). The Normal Fetal and Neonatal Pulmonary Circulation. In: Yuan, JJ., Garcia, J., West, J., Hales, C., Rich, S., Archer, S. (eds) Textbook of Pulmonary Vascular Disease. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-87429-6_9

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