Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Pediatric Pulmonary Hypertension: Definitions, Mechanisms, Diagnosis, and Treatment

Devashis Mukherjee, Girija G. Konduri

10.1002/cphy.c200023

Source: Volume 11, Issue 3, July 2021

Published online: June 2021

Full Article on Wiley Online Library



Abstract

Pediatric pulmonary hypertension (PPH) is a multifactorial disease with diverse etiologies and presenting features. Pulmonary hypertension (PH), defined as elevated pulmonary artery pressure, is the presenting feature for several pulmonary vascular diseases. It is often a hidden component of other lung diseases, such as cystic fibrosis and bronchopulmonary dysplasia. Alterations in lung development and genetic conditions are an important contributor to pediatric pulmonary hypertensive disease, which is a distinct entity from adult PH. Many of the causes of pediatric PH have prenatal onset with altered lung development due to maternal and fetal conditions. Since lung growth is altered in several conditions that lead to PPH, therapy for PPH includes both pulmonary vasodilators and strategies to restore lung growth. These strategies include optimal alveolar recruitment, maintaining physiologic blood gas tension, nutritional support, and addressing contributing factors, such as airway disease and gastroesophageal reflux. The outcome for infants and children with PH is highly variable and largely dependent on the underlying cause. The best outcomes are for neonates with persistent pulmonary hypertension (PPHN) and reversible lung diseases, while some genetic conditions such as alveolar capillary dysplasia are lethal. © 2021 American Physiological Society. Compr Physiol 11:2135‐2190, 2021.

Figure 1. Figure 1. Pathogenesis of bronchopulmonary dysplasia (BPD) associated pulmonary hypertension. The figure highlights the contribution of both prenatal and postnatal factors to the evolution of BPD. ECM, extracellular matrix; SMC, smooth muscle cell.
Figure 2. Figure 2. Molecular and structural mechanisms of pulmonary vascular disease. PGI2, prostacyclin; NO, nitric oxide; sGC, soluble guanylate cyclase; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; PDE, phosphodiesterase; Kv channel, voltage‐gated potassium channel; ET‐1, endothelin‐1; 5HT, 5‐hydroxytryptamine; TRPC, transient receptor potential cation channel; VDCC, voltage‐dependent calcium channel; BMPR2, bone morphogenetic protein receptor‐2; PPAR‐γ, peroxisome proliferator‐activated receptor‐γ; PDGF, platelet‐derived growth factor; FGF, fibroblast growth factor; MMP, matrix metalloproteinase; HIF‐1α, hypoxia inducible factor‐1α; VEGF, vascular endothelial growth factor.
Figure 3. Figure 3. NO‐cGMP pathway showing paracrine effect of endothelial NO on vascular smooth muscle cell. NO, nitric oxide; NOS, nitric oxide synthase; BH4, tetrahydrobiopterin; sGC, soluble guanylate cyclase; GTP, guanosine triphosphate; cGMP, cyclic guanosine monophsphate; PDE, phosphodiesterase; PDE5i, PDE5 inhibitor; PKG, protein kinase G; MYTP, myosin phsophatase targeting subunit; MLCK, myosin light chain kinase; ROCK, Rho kinase.
Figure 4. Figure 4. Prostacyclin pathway role in pulmonary hypertension. AA, arachidonic acid; COX, cyclooxygenase; PGE2, prostaglandin E2; PGI2, prostacyclin; IP, inositol phosphate; PDE, phosphodiesterase; ATP, adenosine triphosphate; AMP, adenosine monophosphate; cAMP, cyclic AMP; SMC, smooth muscle cell; PKA, protein kinase A.
Figure 5. Figure 5. Role of reactive oxygen species in pulmonary hypertension. O2•−, superoxide anion; H2O2, hydrogen peroxide; PDE5, phosphodiesterase‐5; GMP, guanosine monophosphate; cGMP, cyclic GMP; GTP, guanosine triphosphate; H2O, water; NO, nitric oxide; OONO•−, peroxynitrite; SOD, superoxide dismutase; BH4, tetrahydrobiopterin; BH2, dihydrobiopterin; NOS, nitric oxide synthase; eNOS, endothelial NOS; NADPH, nicotinamide adenine dinucleotide phosphate dehydrogenase. Reused, with permission, from Apitz C, et al., 2016 25; Reused, with permission, from Dennis KE, et al., 2009 148; Reused, with permission, from Fike CD, et al., 2008 181; Reused, with permission, from Irodova NL, et al., 2002 267; Reused, with permission, from Wedgwood S and Black SM, 2003 620.
Figure 6. Figure 6. A schematic representation of the BMPR2 signaling pathway. ActR, activin Receptor; Akt, protein kinase b; ALK, activin‐like receptor; BMP, bone morphogenetic protein; BMPR, bone morphogenetic protein receptor; BRE, BMP response element; c‐Src, proto‐oncogene tyrosine‐protein kinase Src; CLIC4, chloride intracellular channel 4; Dvl, disheveled; Erk, extracellular signal‐regulated kinase; FKBP1A, FK binding protein 1A; GSK3‐β, glycogen synthase kinase 3‐β; ID, inhibitor of differentiation; JNK, c‐Jun N‐terminal kinase; LIMK, Lin11, Isl‐1, and Mec‐3 domain kinase; MAPK, mitogen‐activated protein kinase; PI3K, phosphoinositide 3‐kinase; PPARγ, peroxisome proliferator‐activated receptor gamma; Rac1, Ras‐related C3 botulinum toxin substrate 1; RAGE, receptor for advanced glycation end products; RhoA, Ras homolog gene family, member A; SMAD, mothers against decapentaplegic; SMURF, SMAD‐specific E3 ubiquitin protein ligase; Tak1, transforming growth factor‐β activated kinase 1; VEGFR3, vascular endothelial growth factor receptor 3. Modified, with permission, from Andruska, A et al., 2018 23. Licensed under CC‐BY‐4.0.
Figure 7. Figure 7. Diagnostic algorithm for a child or young adult with suspected pulmonary hypertension. PH, pulmonary hypertension; ECG, electrocardiogram; CHD, congenital heart disease; PFT, pulmonary function test; CT, computed tomography; DLCO, diffusing capacity for carbon monoxide; RV, right ventricle; CTEPH, chronic thromboembolic pulmonary hypertension; CTA, CT angiogram; PA, pulmonary artery; PEA, pulmonary endarterectomy; AVT, acute vasoreactivity testing; mPAP, mean pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; PVRI, pulmonary vascular resistance index; WU, Wood units; 6MWT, 6‐minute walk test; MRI, magnetic resonance imaging; CPET, cardiopulmonary exercise testing; CTD, connective tissue disease; HIV, human immunodeficiency virus; PVOD, pulmonary veno‐occlusive disease; PCH, pulmonary capillary hemangiomatosis; IPAH, idiopathic pulmonary arterial hypertension; FPAH, familial pulmonary arterial hypertension. Adapted, with permission, from Rosenzweig EB, et al., 2019 506. © 2019, The European Respiratory Society.
Figure 8. Figure 8. Two‐dimensional echocardiogram of a patient with severe PAH in the parasternal short‐axis view showing D‐shaped left ventricle (yellow line) and severe right ventricular dilatation (red line), along with biventricular remodelling.
Figure 9. Figure 9. Treatment algorithm for pediatric IPAH/HPAH as recommended by the 6th WSPH Pediatric Task Force. ERA, endothelin receptor antagonist; PDE5, phosphodiesterase 5; i.v., intravenous; s.c, subcutaneous. Adapted, with permission, from Rosenzweig EB, et al., 2019 506. © 2019, The European Respiratory Society.
Figure 10. Figure 10. Algorithm for the diagnosis and treatment of pulmonary hypertension in infants with bronchopulmonary dysplasia based on recommendations from PPHNet. PPHNet, pediatric pulmonary hypertension network; BPD, bronchopulmonary dysplasia; PH, pulmonary hypertension; ECHO, echocardiogram; PAP, pulmonary arterial pressure; SAP, systemic arterial pressure; BNP, brain‐type natriuretic peptide; NT‐proBNP, N‐terminal proBNP; PVS, pulmonary vein stenosis; LVDD, left ventricular diastolic dysfunction; APC, aortopulmonary collateral. Modified, with permission, from Krishnan U, et al., 2017 320.


Figure 1. Pathogenesis of bronchopulmonary dysplasia (BPD) associated pulmonary hypertension. The figure highlights the contribution of both prenatal and postnatal factors to the evolution of BPD. ECM, extracellular matrix; SMC, smooth muscle cell.


Figure 2. Molecular and structural mechanisms of pulmonary vascular disease. PGI2, prostacyclin; NO, nitric oxide; sGC, soluble guanylate cyclase; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; PDE, phosphodiesterase; Kv channel, voltage‐gated potassium channel; ET‐1, endothelin‐1; 5HT, 5‐hydroxytryptamine; TRPC, transient receptor potential cation channel; VDCC, voltage‐dependent calcium channel; BMPR2, bone morphogenetic protein receptor‐2; PPAR‐γ, peroxisome proliferator‐activated receptor‐γ; PDGF, platelet‐derived growth factor; FGF, fibroblast growth factor; MMP, matrix metalloproteinase; HIF‐1α, hypoxia inducible factor‐1α; VEGF, vascular endothelial growth factor.


Figure 3. NO‐cGMP pathway showing paracrine effect of endothelial NO on vascular smooth muscle cell. NO, nitric oxide; NOS, nitric oxide synthase; BH4, tetrahydrobiopterin; sGC, soluble guanylate cyclase; GTP, guanosine triphosphate; cGMP, cyclic guanosine monophsphate; PDE, phosphodiesterase; PDE5i, PDE5 inhibitor; PKG, protein kinase G; MYTP, myosin phsophatase targeting subunit; MLCK, myosin light chain kinase; ROCK, Rho kinase.


Figure 4. Prostacyclin pathway role in pulmonary hypertension. AA, arachidonic acid; COX, cyclooxygenase; PGE2, prostaglandin E2; PGI2, prostacyclin; IP, inositol phosphate; PDE, phosphodiesterase; ATP, adenosine triphosphate; AMP, adenosine monophosphate; cAMP, cyclic AMP; SMC, smooth muscle cell; PKA, protein kinase A.


Figure 5. Role of reactive oxygen species in pulmonary hypertension. O2•−, superoxide anion; H2O2, hydrogen peroxide; PDE5, phosphodiesterase‐5; GMP, guanosine monophosphate; cGMP, cyclic GMP; GTP, guanosine triphosphate; H2O, water; NO, nitric oxide; OONO•−, peroxynitrite; SOD, superoxide dismutase; BH4, tetrahydrobiopterin; BH2, dihydrobiopterin; NOS, nitric oxide synthase; eNOS, endothelial NOS; NADPH, nicotinamide adenine dinucleotide phosphate dehydrogenase. Reused, with permission, from Apitz C, et al., 2016 25; Reused, with permission, from Dennis KE, et al., 2009 148; Reused, with permission, from Fike CD, et al., 2008 181; Reused, with permission, from Irodova NL, et al., 2002 267; Reused, with permission, from Wedgwood S and Black SM, 2003 620.


Figure 6. A schematic representation of the BMPR2 signaling pathway. ActR, activin Receptor; Akt, protein kinase b; ALK, activin‐like receptor; BMP, bone morphogenetic protein; BMPR, bone morphogenetic protein receptor; BRE, BMP response element; c‐Src, proto‐oncogene tyrosine‐protein kinase Src; CLIC4, chloride intracellular channel 4; Dvl, disheveled; Erk, extracellular signal‐regulated kinase; FKBP1A, FK binding protein 1A; GSK3‐β, glycogen synthase kinase 3‐β; ID, inhibitor of differentiation; JNK, c‐Jun N‐terminal kinase; LIMK, Lin11, Isl‐1, and Mec‐3 domain kinase; MAPK, mitogen‐activated protein kinase; PI3K, phosphoinositide 3‐kinase; PPARγ, peroxisome proliferator‐activated receptor gamma; Rac1, Ras‐related C3 botulinum toxin substrate 1; RAGE, receptor for advanced glycation end products; RhoA, Ras homolog gene family, member A; SMAD, mothers against decapentaplegic; SMURF, SMAD‐specific E3 ubiquitin protein ligase; Tak1, transforming growth factor‐β activated kinase 1; VEGFR3, vascular endothelial growth factor receptor 3. Modified, with permission, from Andruska, A et al., 2018 23. Licensed under CC‐BY‐4.0.


Figure 7. Diagnostic algorithm for a child or young adult with suspected pulmonary hypertension. PH, pulmonary hypertension; ECG, electrocardiogram; CHD, congenital heart disease; PFT, pulmonary function test; CT, computed tomography; DLCO, diffusing capacity for carbon monoxide; RV, right ventricle; CTEPH, chronic thromboembolic pulmonary hypertension; CTA, CT angiogram; PA, pulmonary artery; PEA, pulmonary endarterectomy; AVT, acute vasoreactivity testing; mPAP, mean pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; PVRI, pulmonary vascular resistance index; WU, Wood units; 6MWT, 6‐minute walk test; MRI, magnetic resonance imaging; CPET, cardiopulmonary exercise testing; CTD, connective tissue disease; HIV, human immunodeficiency virus; PVOD, pulmonary veno‐occlusive disease; PCH, pulmonary capillary hemangiomatosis; IPAH, idiopathic pulmonary arterial hypertension; FPAH, familial pulmonary arterial hypertension. Adapted, with permission, from Rosenzweig EB, et al., 2019 506. © 2019, The European Respiratory Society.


Figure 8. Two‐dimensional echocardiogram of a patient with severe PAH in the parasternal short‐axis view showing D‐shaped left ventricle (yellow line) and severe right ventricular dilatation (red line), along with biventricular remodelling.


Figure 9. Treatment algorithm for pediatric IPAH/HPAH as recommended by the 6th WSPH Pediatric Task Force. ERA, endothelin receptor antagonist; PDE5, phosphodiesterase 5; i.v., intravenous; s.c, subcutaneous. Adapted, with permission, from Rosenzweig EB, et al., 2019 506. © 2019, The European Respiratory Society.


Figure 10. Algorithm for the diagnosis and treatment of pulmonary hypertension in infants with bronchopulmonary dysplasia based on recommendations from PPHNet. PPHNet, pediatric pulmonary hypertension network; BPD, bronchopulmonary dysplasia; PH, pulmonary hypertension; ECHO, echocardiogram; PAP, pulmonary arterial pressure; SAP, systemic arterial pressure; BNP, brain‐type natriuretic peptide; NT‐proBNP, N‐terminal proBNP; PVS, pulmonary vein stenosis; LVDD, left ventricular diastolic dysfunction; APC, aortopulmonary collateral. Modified, with permission, from Krishnan U, et al., 2017 320.
References
 1.Abe K, Shimokawa H, Morikawa K, Uwatoku T, Oi K, Matsumoto Y, Hattori T, Nakashima Y, Kaibuchi K, Sueishi K, Takeshit A. Long‐term treatment with a Rho‐kinase inhibitor improves monocrotaline‐induced fatal pulmonary hypertension in rats. Circ Res 94: 385‐393, 2004.
 2.Abman SH. Bronchopulmonary dysplasia: “A vascular hypothesis”. Am J Respir Crit Care Med 164: 1755‐1756, 2001.
 3.Abman SH, Accurso FJ, Koops BL. Experience with home oxygen in the management of infants with bronchopulmonary dysplasia. Clin Pediatr (Phila) 23: 471‐476, 1984.
 4.Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, Hanna BD, Rosenzweig EB, Raj JU, Cornfield D, Stenmark KR, Steinhorn R, Thebaud B, Fineman JR, Kuehne T, Feinstein JA, Friedberg MK, Earing M, Barst RJ, Keller RL, Kinsella JP, Mullen M, Deterding R, Kulik T, Mallory G, Humpl T, Wessel DL, American Heart Association Council on Cardiopulmonary CCP, Resuscitation, Council on Clinical C, Council on Cardiovascular Disease in the Y, Council on Cardiovascular R, Intervention, Council on Cardiovascular S, Anesthesia, and the American Thoracic S. Pediatric pulmonary hypertension: Guidelines from the American heart association and American thoracic society. Circulation 132: 2037‐2099, 2015.
 5.Abman SH, Kinsella JP, Rosenzweig EB, Krishnan U, Kulik T, Mullen M, Wessel DL, Steinhorn R, Adatia I, Hanna B, Feinstein J, Fineman J, Raj U, Humpl T, Pediatric Pulmonary Hypertension N. Implications of the U.S. Food and Drug Administration warning against the use of sildenafil for the treatment of pediatric pulmonary hypertension. Am J Respir Crit Care Med 187: 572‐575, 2013.
 6.Abman SH, Wolfe RR, Accurso FJ, Koops BL, Bowman CM, Wiggins JW Jr. Pulmonary vascular response to oxygen in infants with severe bronchopulmonary dysplasia. Pediatrics 75: 80‐84, 1985.
 7.Abou Hassan OK, Haidar W, Arabi M, Skouri H, Bitar F, Nemer G, Akl IB. Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension. BMC Med Genet 20: 176, 2019.
 8.Abumehdi MR, Wardle AJ, Nazzal R, Charalampopoulos A, Schulze‐Neick I, Derrick G, Moledina S, Giardini A. Feasibility and safety of cardiopulmonary exercise testing in children with pulmonary hypertension. Cardiol Young 26: 1144‐1150, 2016.
 9.Acker SN, Seedorf GJ, Abman SH, Nozik‐Grayck E, Partrick DA, Gien J. Pulmonary artery endothelial cell dysfunction and decreased populations of highly proliferative endothelial cells in experimental congenital diaphragmatic hernia. Am J Physiol Lung Cell Mol Physiol 305: L943‐L952, 2013.
 10.Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid‐19. N Engl J Med 383: 120‐128, 2020.
 11.Afolayan AJ, Eis A, Alexander M, Michalkiewicz T, Teng RJ, Lakshminrusimha S, Konduri GG. Decreased endothelial nitric oxide synthase expression and function contribute to impaired mitochondrial biogenesis and oxidative stress in fetal lambs with persistent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 310: L40‐L49, 2016.
 12.Aggarwal M, Grady RM, Choudhry S, Anwar S, Eghtesady P, Singh GK. Potts shunt improves right ventricular function and coupling with pulmonary circulation in children with suprasystemic pulmonary arterial hypertension. Circ Cardiovasc Imaging 11: e007964, 2018.
 13.Ahmad KA, Banales J, Henderson CL, Ramos SE, Brandt KM, Powers GC. Intravenous epoprostenol improves oxygenation index in patients with persistent pulmonary hypertension of the newborn refractory to nitric oxide. J Perinatol 38: 1212‐1219, 2018.
 14.Ahmed MN, Suliman HB, Folz RJ, Nozik‐Grayck E, Golson ML, Mason SN, Auten RL. Extracellular superoxide dismutase protects lung development in hyperoxia‐exposed newborn mice. Am J Respir Crit Care Med 167: 400‐405, 2003.
 15.Aldred MA, Vijayakrishnan J, James V, Soubrier F, Gomez‐Sanchez MA, Martensson G, Galie N, Manes A, Corris P, Simonneau G, Humbert M, Morrell NW, Trembath RC. BMPR2 gene rearrangements account for a significant proportion of mutations in familial and idiopathic pulmonary arterial hypertension. Hum Mutat 27: 212‐213, 2006.
 16.Alfranca A, Iniguez MA, Fresno M, Redondo JM. Prostanoid signal transduction and gene expression in the endothelium: Role in cardiovascular diseases. Cardiovasc Res 70: 446‐456, 2006.
 17.Alkon J, Humpl T, Manlhiot C, McCrindle BW, Reyes JT, Friedberg MK. Usefulness of the right ventricular systolic to diastolic duration ratio to predict functional capacity and survival in children with pulmonary arterial hypertension. Am J Cardiol 106: 430‐436, 2010.
 18.Alvira CM. Aberrant pulmonary vascular growth and remodeling in bronchopulmonary dysplasia. Front Med (Lausanne) 3: 21, 2016.
 19.Ambalavanan N, Bulger A, Murphy‐Ullrich J, Oparil S, Chen YF. Endothelin‐A receptor blockade prevents and partially reverses neonatal hypoxic pulmonary vascular remodeling. Pediatr Res 57: 631‐636, 2005.
 20.Ambalavanan N, Mariani G, Bulger A, Philips IJ. Role of nitric oxide in regulating neonatal porcine pulmonary artery smooth muscle cell proliferation. Biol Neonate 76: 291‐300, 1999.
 21.Amoozgar H, Banafi P, Mohammadi H, Edraki MR, Mehdizadegan N, Ajami G, Borzouee M, Keshaarz K, Moradi P, Dehghani E. Management of persistent pulmonary hypertension after correction of congenital heart defect with autologous marrow‐derived mononuclear stem cell injection into the pulmonary artery: A pilot study. Pediatr Cardiol 41: 398‐406, 2020.
 22.Andrae J, Gallini R, Betsholtz C. Role of platelet‐derived growth factors in physiology and medicine. Genes Dev 22: 1276‐1312, 2008.
 23.Andruska A, Spiekerkoetter E. Consequences of BMPR2 deficiency in the pulmonary vasculature and beyond: Contributions to pulmonary arterial hypertension. Int J Mol Sci 19: 2499, 2018.
 24.Antoniu SA. Targeting PDGF pathway in pulmonary arterial hypertension. Expert Opin Ther Targets 16: 1055‐1063, 2012.
 25.Apitz C, Hansmann G, Schranz D. Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 102 (Suppl 2): ii23‐ii29, 2016.
 26.Archer S, Rich S. Primary pulmonary hypertension: A vascular biology and translational research “Work in progress”. Circulation 102: 2781‐2791, 2000.
 27.Arcot SS, Lipke DW, Gillespie MN, Olson JW. Alterations of growth factor transcripts in rat lungs during development of monocrotaline‐induced pulmonary hypertension. Biochem Pharmacol 46: 1086‐1091, 1993.
 28.Arjaans S, Wagner BD, Mourani PM, Mandell EW, Poindexter BB, Berger RMF, Abman SH. Early angiogenic proteins associated with high risk for bronchopulmonary dysplasia and pulmonary hypertension in preterm infants. Am J Physiol Lung Cell Mol Physiol 318: L644‐L654, 2020.
 29.Arjaans S, Zwart EAH, Ploegstra MJ, Bos AF, Kooi EMW, Hillege HL, Berger RMF. Identification of gaps in the current knowledge on pulmonary hypertension in extremely preterm infants: A systematic review and meta‐analysis. Paediatr Perinat Epidemiol 32: 258‐267, 2018.
 30.Askie LM, Darlow BA, Finer N, Schmidt B, Stenson B, Tarnow‐Mordi W, Davis PG, Carlo WA, Brocklehurst P, Davies LC, Das A, Rich W, Gantz MG, Roberts RS, Whyte RK, Costantini L, Poets C, Asztalos E, Battin M, Halliday HL, Marlow N, Tin W, King A, Juszczak E, Morley CJ, Doyle LW, Gebski V, Hunter KE, Simes RJ, Neonatal Oxygenation Prospective Meta‐analysis C. Association between oxygen saturation targeting and death or disability in extremely preterm infants in the neonatal oxygenation prospective meta‐analysis collaboration. JAMA 319: 2190‐2201, 2018.
 31.Assad TR, Hemnes AR, Larkin EK, Glazer AM, Xu M, Wells QS, Farber‐Eger EH, Sheng Q, Shyr Y, Harrell FE, Newman JH, Brittain EL. Clinical and biological insights Into combined post‐ and pre‐capillary pulmonary hypertension. J Am Coll Cardiol 68: 2525‐2536, 2016.
 32.Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 105: 1672‐1678, 2002.
 33.Atz AM, Adatia I, Lock JE, Wessel DL. Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator testing. J Am Coll Cardiol 33: 813‐819, 1999.
 34.Atz AM, Lefler AK, Fairbrother DL, Uber WE, Bradley SM. Sildenafil augments the effect of inhaled nitric oxide for postoperative pulmonary hypertensive crises. J Thorac Cardiovasc Surg 124: 628‐629, 2002.
 35.Austin ED, Loyd JE. The genetics of pulmonary arterial hypertension. Circ Res 115: 189‐202, 2014.
 36.Australia B‐I, United Kingdom Collaborative G, Tarnow‐Mordi W, Stenson B, Kirby A, Juszczak E, Donoghoe M, Deshpande S, Morley C, King A, Doyle LW, Fleck BW, Davis PG, Halliday HL, Hague W, Cairns P, Darlow BA, Fielder AR, Gebski V, Marlow N, Simmer K, Tin W, Ghadge A, Williams C, Keech A, Wardle SP, Kecskes Z, Kluckow M, Gole G, Evans N, Malcolm G, Luig M, Wright I, Stack J, Tan K, Pritchard M, Gray PH, Morris S, Headley B, Dargaville P, Simes RJ, Brocklehurst P. Outcomes of two trials of oxygen‐saturation targets in preterm infants. N Engl J Med 374: 749‐760, 2016.
 37.Avitabile CM, Vorhies EE, Ivy DD. Drug treatment of pulmonary hypertension in children. Paediatr Drugs 22: 123‐147, 2020.
 38.Badesch DB, Champion HC, Sanchez MA, Hoeper MM, Loyd JE, Manes A, McGoon M, Naeije R, Olschewski H, Oudiz RJ, Torbicki A. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 54: S55‐S66, 2009.
 39.Baker CD, Abman SH. Impaired pulmonary vascular development in bronchopulmonary dysplasia. Neonatology 107: 344‐351, 2015.
 40.Baker CD, Abman SH, Mourani PM. Pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. Pediatr Allergy Immunol Pulmonol 27: 8‐16, 2014.
 41.Balasubramaniam V, Le Cras TD, Ivy DD, Grover TR, Kinsella JP, Abman SH. Role of platelet‐derived growth factor in vascular remodeling during pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 284: L826‐L833, 2003.
 42.Ballard RA, Truog WE, Cnaan A, Martin RJ, Ballard PL, Merrill JD, Walsh MC, Durand DJ, Mayock DE, Eichenwald EC, Null DR, Hudak ML, Puri AR, Golombek SG, Courtney SE, Stewart DL, Welty SE, Phibbs RH, Hibbs AM, Luan X, Wadlinger SR, Asselin JM, Coburn CE, Group NCS. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med 355: 343‐353, 2006.
 43.Baquero H, Soliz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: A pilot randomized blinded study. Pediatrics 117: 1077‐1083, 2006.
 44.Barefield ES, Karle VA, Phillips JB 3rd, Carlo WA. Inhaled nitric oxide in term infants with hypoxemic respiratory failure. J Pediatr 129: 279‐286, 1996.
 45.Barnett CF, Hsue PY, Machado RF. Pulmonary hypertension: An increasingly recognized complication of hereditary hemolytic anemias and HIV infection. JAMA 299: 324‐331, 2008.
 46.Barrington KJ, Finer N, Pennaforte T. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev 1: CD000509, 2017.
 47.Barrington KJ, Finer N, Pennaforte T, Altit G. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev 1: CD000399, 2017.
 48.Barst RJ. Role of atrial septostomy in the treatment of pulmonary vascular disease. Thorax 55: 95‐96, 2000.
 49.Barst RJ, Agnoletti G, Fraisse A, Baldassarre J, Wessel DL, Group NODS. Vasodilator testing with nitric oxide and/or oxygen in pediatric pulmonary hypertension. Pediatr Cardiol 31: 598‐606, 2010.
 50.Barst RJ, Beghetti M, Pulido T, Layton G, Konourina I, Zhang M, Ivy DD, Investigators S. STARTS‐2: Long‐term survival with oral sildenafil monotherapy in treatment‐naive pediatric pulmonary arterial hypertension. Circulation 129: 1914‐1923, 2014.
 51.Barst RJ, Channick R, Ivy D, Goldstein B. Clinical perspectives with long‐term pulsed inhaled nitric oxide for the treatment of pulmonary arterial hypertension. Pulm Circ 2: 139‐147, 2012.
 52.Barst RJ, Galie N, Naeije R, Simonneau G, Jeffs R, Arneson C, Rubin LJ. Long‐term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil. Eur Respir J 28: 1195‐1203, 2006.
 53.Barst RJ, Gibbs JS, Ghofrani HA, Hoeper MM, McLaughlin VV, Rubin LJ, Sitbon O, Tapson VF, Galie N. Updated evidence‐based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol 54: S78‐S84, 2009.
 54.Barst RJ, Ivy D, Dingemanse J, Widlitz A, Schmitt K, Doran A, Bingaman D, Nguyen N, Gaitonde M, van Giersbergen PL. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin Pharmacol Ther 73: 372‐382, 2003.
 55.Barst RJ, Ivy DD, Gaitan G, Szatmari A, Rudzinski A, Garcia AE, Sastry BK, Pulido T, Layton GR, Serdarevic‐Pehar M, Wessel DL. A randomized, double‐blind, placebo‐controlled, dose‐ranging study of oral sildenafil citrate in treatment‐naive children with pulmonary arterial hypertension. Circulation 125: 324‐334, 2012.
 56.Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for primary pulmonary hypertension in children. Circulation 99: 1197‐1208, 1999.
 57.Barst RJ, McGoon M, McLaughlin V, Tapson V, Rich S, Rubin L, Wasserman K, Oudiz R, Shapiro S, Robbins IM, Channick R, Badesch D, Rayburn BK, Flinchbaugh R, Sigman J, Arneson C, Jeffs R, Beraprost Study G. Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol 41: 2119‐2125, 2003.
 58.Barst RJ, McGoon MD, Elliott CG, Foreman AJ, Miller DP, Ivy DD. Survival in childhood pulmonary arterial hypertension: Insights from the registry to evaluate early and long‐term pulmonary arterial hypertension disease management. Circulation 125: 113‐122, 2012.
 59.Baruteau AE, Belli E, Boudjemline Y, Laux D, Levy M, Simonneau G, Carotti A, Humbert M, Bonnet D. Palliative Potts shunt for the treatment of children with drug‐refractory pulmonary arterial hypertension: Updated data from the first 24 patients. Eur J Cardiothorac Surg 47: e105‐e110, 2015.
 60.Bauer NR, Moore TM, McMurtry IF. Rodent models of PAH: Are we there yet? Am J Physiol Lung Cell Mol Physiol 293: L580‐L582, 2007.
 61.Beghetti M, Berger RM, Schulze‐Neick I, Day RW, Pulido T, Feinstein J, Barst RJ, Humpl T, Investigators TR. Diagnostic evaluation of paediatric pulmonary hypertension in current clinical practice. Eur Respir J 42: 689‐700, 2013.
 62.Beghetti M, Brand M, Berger RMF, Humpl T, Wheeler JG, Ivy DD, Bonnet D, investigators T. Meaningful and feasible composite clinical worsening definitions in paediatric pulmonary arterial hypertension: An analysis of the TOPP registry. Int J Cardiol 289: 110‐115, 2019.
 63.Beghetti M, Habre W, Friedli B, Berner M. Continuous low dose inhaled nitric oxide for treatment of severe pulmonary hypertension after cardiac surgery in paediatric patients. Br Heart J 73: 65‐68, 1995.
 64.Beghetti M, Haworth SG, Bonnet D, Barst RJ, Acar P, Fraisse A, Ivy DD, Jais X, Schulze‐Neick I, Galie N, Morganti A, Dingemanse J, Kusic‐Pajic A, Berger RM. Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: The FUTURE‐1 study. Br J Clin Pharmacol 68: 948‐955, 2009.
 65.Benigni A, Remuzzi G. Endothelin antagonists. Lancet 353: 133‐138, 1999.
 66.Benisty JI, McLaughlin VV, Landzberg MJ, Rich JD, Newburger JW, Rich S, Folkman J. Elevated basic fibroblast growth factor levels in patients with pulmonary arterial hypertension. Chest 126: 1255‐1261, 2004.
 67.Benza R, Biederman R, Murali S, Gupta H. Role of cardiac magnetic resonance imaging in the management of patients with pulmonary arterial hypertension. J Am Coll Cardiol 52: 1683‐1692, 2008.
 68.Benza RL, Miller DP, Gomberg‐Maitland M, Frantz RP, Foreman AJ, Coffey CS, Frost A, Barst RJ, Badesch DB, Elliott CG, Liou TG, McGoon MD. Predicting survival in pulmonary arterial hypertension: Insights from the Registry to Evaluate Early and Long‐Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 122: 164‐172, 2010.
 69.Berger RM, Beghetti M, Humpl T, Raskob GE, Ivy DD, Jing ZC, Bonnet D, Schulze‐Neick I, Barst RJ. Clinical features of paediatric pulmonary hypertension: A registry study. Lancet 379: 537‐546, 2012.
 70.Berger RM, Haworth SG, Bonnet D, Dulac Y, Fraisse A, Galie N, Ivy DD, Jais X, Miera O, Rosenzweig EB, Efficace M, Kusic‐Pajic A, Beghetti M. FUTURE‐2: Results from an open‐label, long‐term safety and tolerability extension study using the pediatric FormUlation of bosenTan in pUlmonary arterial hypeRtEnsion. Int J Cardiol 202: 52‐58, 2016.
 71.Berger RMF, Gehin M, Beghetti M, Ivy D, Kusic‐Pajic A, Cornelisse P, Grill S, Bonnet D, investigators F. A bosentan pharmacokinetic study to investigate dosing regimens in paediatric patients with pulmonary arterial hypertension: FUTURE‐3. Br J Clin Pharmacol 83: 1734‐1744, 2017.
 72.Berger‐Caron F, Piedboeuf B, Morissette G, Simonyan D, Chetaille P, Pellerin A, Hebert A. Inhaled epoprostenol for pulmonary hypertension treatment in neonates: A 12‐year experience. Am J Perinatol 36: 1142‐1149, 2019.
 73.Berk BC. Vascular smooth muscle growth: Autocrine growth mechanisms. Physiol Rev 81: 999‐1030, 2001.
 74.Berkelhamer SK, Kim GA, Radder JE, Wedgwood S, Czech L, Steinhorn RH, Schumacker PT. Developmental differences in hyperoxia‐induced oxidative stress and cellular responses in the murine lung. Free Radic Biol Med 61: 51‐60, 2013.
 75.Berkelhamer SK, Mestan KK, Steinhorn R. An update on the diagnosis and management of bronchopulmonary dysplasia (BPD)‐associated pulmonary hypertension. Semin Perinatol 42: 432‐443, 2018.
 76.Berman EB, Barst RJ. Eisenmenger's syndrome: Current management. Prog Cardiovasc Dis 45: 129‐138, 2002.
 77.Bertero T, Oldham WM, Cottrill KA, Pisano S, Vanderpool RR, Yu Q, Zhao J, Tai Y, Tang Y, Zhang YY, Rehman S, Sugahara M, Qi Z, Gorcsan J 3rd, Vargas SO, Saggar R, Saggar R, Wallace WD, Ross DJ, Haley KJ, Waxman AB, Parikh VN, De Marco T, Hsue PY, Morris A, Simon MA, Norris KA, Gaggioli C, Loscalzo J, Fessel J, Chan SY. Vascular stiffness mechanoactivates YAP/TAZ‐dependent glutaminolysis to drive pulmonary hypertension. J Clin Invest 126: 3313‐3335, 2016.
 78.Best DH, Sumner KL, Austin ED, Chung WK, Brown LM, Borczuk AC, Rosenzweig EB, Bayrak‐Toydemir P, Mao R, Cahill BC, Tazelaar HD, Leslie KO, Hemnes AR, Robbins IM, Elliott CG. EIF2AK4 mutations in pulmonary capillary hemangiomatosis. Chest 145: 231‐236, 2014.
 79.Bhatt AJ, Pryhuber GS, Huyck H, Watkins RH, Metlay LA, Maniscalco WM. Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt‐1, and TIE‐2 in human infants dying with bronchopulmonary dysplasia. Am J Respir Crit Care Med 164: 1971‐1980, 2001.
 80.Bijli KM, Kleinhenz JM, Murphy TC, Kang BY, Adesina SE, Sutliff RL, Hart CM. Peroxisome proliferator‐activated receptor gamma depletion stimulates Nox4 expression and human pulmonary artery smooth muscle cell proliferation. Free Radic Biol Med 80: 111‐120, 2015.
 81.Bishop NB, Stankiewicz P, Steinhorn RH. Alveolar capillary dysplasia. Am J Respir Crit Care Med 184: 172‐179, 2011.
 82.Blanc J, Vouhe P, Bonnet D. Potts shunt in patients with pulmonary hypertension. N Engl J Med 350: 623, 2004.
 83.Blyth KG, Groenning BA, Mark PB, Martin TN, Foster JE, Steedman T, Morton JJ, Dargie HJ, Peacock AJ. NT‐proBNP can be used to detect right ventricular systolic dysfunction in pulmonary hypertension. Eur Respir J 29: 737‐744, 2007.
 84.Bobhate P, Guo L, Jain S, Haugen R, Coe JY, Cave D, Rutledge J, Adatia I. Cardiac catheterization in children with pulmonary hypertensive vascular disease. Pediatr Cardiol 36: 873‐879, 2015.
 85.Boehm M, Arnold N, Braithwaite A, Pickworth J, Lu C, Novoyatleva T, Kiely DG, Grimminger F, Ghofrani HA, Weissmann N, Seeger W, Lawrie A, Schermuly RT, Kojonazarov B. Eplerenone attenuates pathological pulmonary vascular rather than right ventricular remodeling in pulmonary arterial hypertension. BMC Pulm Med 18: 41, 2018.
 86.Bogaard HJ, Abe K, Vonk Noordegraaf A, Voelkel NF. The right ventricle under pressure: Cellular and molecular mechanisms of right‐heart failure in pulmonary hypertension. Chest 135: 794‐804, 2009.
 87.Boudjemline Y, Patel M, Malekzadeh‐Milani S, Szezepanski I, Levy M, Bonnet D. Patent ductus arteriosus stenting (transcatheter Potts shunt) for palliation of suprasystemic pulmonary arterial hypertension: A case series. Circ Cardiovasc Interv 6: e18‐e20, 2013.
 88.Boudjemline Y, Sizarov A, Malekzadeh‐Milani S, Mirabile C, Lenoir M, Khraiche D, Levy M, Bonnet D. Safety and feasibility of the transcatheter approach to create a reverse potts shunt in children with idiopathic pulmonary arterial hypertension. Can J Cardiol 33: 1188‐1196, 2017.
 89.Bournia VK, Tsangaris I, Rallidis L, Konstantonis D, Frantzeskaki F, Anthi A, Orfanos SE, Demerouti E, Karyofillis P, Voudris V, Laskari K, Panopoulos S, Vlachoyiannopoulos PG, Sfikakis PP. Cardiac catheterization versus echocardiography for monitoring pulmonary pressure: A prospective study in patients with connective tissue disease‐associated pulmonary arterial hypertension. Diagnostics (Basel) 10: 49, 2020.
 90.Bradlow WM, Assomull R, Kilner PJ, Gibbs JS, Sheppard MN, Mohiaddin RH. Understanding late gadolinium enhancement in pulmonary hypertension. Circ Cardiovasc Imaging 3: 501‐503, 2010.
 91.Brennan LA, Steinhorn RH, Wedgwood S, Mata‐Greenwood E, Roark EA, Russell JA, Black SM. Increased superoxide generation is associated with pulmonary hypertension in fetal lambs: A role for NADPH oxidase. Circ Res 92: 683‐691, 2003.
 92.Breysem L, Smet MH, Van Lierde S, Devlieger H, De Boeck K. Bronchopulmonary dysplasia: Correlation of radiographic and clinical findings. Pediatr Radiol 27: 642‐646, 1997.
 93.Bronicki RA, Baden HP. Pathophysiology of right ventricular failure in pulmonary hypertension. Pediatr Crit Care Med 11: S15‐S22, 2010.
 94.Broughton BR, Walker BR, Resta TC. Chronic hypoxia induces Rho kinase‐dependent myogenic tone in small pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 294: L797‐L806, 2008.
 95.Bull TM, Coldren CD, Geraci MW, Voelkel NF. Gene expression profiling in pulmonary hypertension. Proc Am Thorac Soc 4: 117‐120, 2007.
 96.Burg ED, Remillard CV, Yuan JX. Potassium channels in the regulation of pulmonary artery smooth muscle cell proliferation and apoptosis: Pharmacotherapeutic implications. Br J Pharmacol 153 (Suppl 1): S99‐S111, 2008.
 97.Burke DL, Frid MG, Kunrath CL, Karoor V, Anwar A, Wagner BD, Strassheim D, Stenmark KR. Sustained hypoxia promotes the development of a pulmonary artery‐specific chronic inflammatory microenvironment. Am J Physiol Lung Cell Mol Physiol 297: L238‐L250, 2009.
 98.Burkett DA, Slorach C, Patel SS, Redington AN, Ivy DD, Mertens L, Younoszai AK, Friedberg MK. Impact of pulmonary hemodynamics and ventricular interdependence on left ventricular diastolic function in children with pulmonary hypertension. Circ Cardiovasc Imaging 9, 2016. DOI: 10.1161/CIRCIMAGING.116.004612.
 99.Bush A, Busst CM, Knight WB, Hislop AA, Haworth SG, Shinebourne EA. Changes in pulmonary circulation in severe bronchopulmonary dysplasia. Arch Dis Child 65: 739‐745, 1990.
 100.Campbell BT, Herbst KW, Briden KE, Neff S, Ruscher KA, Hagadorn JI. Inhaled nitric oxide use in neonates with congenital diaphragmatic hernia. Pediatrics 134: e420‐e426, 2014.
 101.Caravita S, Baratto C, Di Marco F, Calabrese A, Balestrieri G, Russo F, Faini A, Soranna D, Perego GB, Badano LP, Grazioli L, Lorini FL, Parati G, Senni M. Hemodynamic characteristics of COVID‐19 patients with acute respiratory distress syndrome requiring mechanical ventilation. An invasive assessment using right heart catheterization. Eur J Heart Fail 22 (12): 2228‐2237, 2020.
 102.Carmosino MJ, Friesen RH, Doran A, Ivy DD. Perioperative complications in children with pulmonary hypertension undergoing noncardiac surgery or cardiac catheterization. Anesth Analg 104: 521‐527, 2007.
 103.Carter NJ, Keating GM. Bosentan: In pediatric patients with pulmonary arterial hypertension. Paediatr Drugs 12: 63‐73, 2010.
 104.Caruso P, MacLean MR, Khanin R, McClure J, Soon E, Southgate M, MacDonald RA, Greig JA, Robertson KE, Masson R, Denby L, Dempsie Y, Long L, Morrell NW, Baker AH. Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline. Arterioscler Thromb Vasc Biol 30: 716‐723, 2010.
 105.Carvajal JA, Germain AM, Huidobro‐Toro JP, Weiner CP. Molecular mechanism of cGMP‐mediated smooth muscle relaxation. J Cell Physiol 184: 409‐420, 2000.
 106.Cerro MJ, Abman S, Diaz G, Freudenthal AH, Freudenthal F, Harikrishnan S, Haworth SG, Ivy D, Lopes AA, Raj JU, Sandoval J, Stenmark K, Adatia I. A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI Pediatric Taskforce, Panama 2011. Pulm Circ 1: 286‐298, 2011.
 107.Cevik A, Kula S, Olgunturk R, Tunaoglu FS, Oguz AD, Saylan B, Cilsal E, Sanli C. Assessment of pulmonary arterial hypertension and vascular resistance by measurements of the pulmonary arterial flow velocity curve in the absence of a measurable tricuspid regurgitant velocity in childhood congenital heart disease. Pediatr Cardiol 34: 646‐655, 2013.
 108.Chandrasekar I, Eis A, Konduri GG. Betamethasone attenuates oxidant stress in endothelial cells from fetal lambs with persistent pulmonary hypertension. Pediatr Res 63: 67‐72, 2008.
 109.Chandrasekharan P, Lakshminrusimha S. Oxygen therapy in preterm infants with pulmonary hypertension. Semin Fetal Neonatal Med 25: 101070, 2020.
 110.Chandrasekharan P, Rawat M, Gugino SF, Koenigsknecht C, Helman J, Nair J, Vali P, Lakshminrusimha S. Effect of various inspired oxygen concentrations on pulmonary and systemic hemodynamics and oxygenation during resuscitation in a transitioning preterm model. Pediatr Res 84: 743‐750, 2018.
 111.Chang AC, Zucker HA, Hickey PR, Wessel DL. Pulmonary vascular resistance in infants after cardiac surgery: Role of carbon dioxide and hydrogen ion. Crit Care Med 23: 568‐574, 1995.
 112.Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF, Badesch DB, Roux S, Rainisio M, Bodin F, Rubin LJ. Effects of the dual endothelin‐receptor antagonist bosentan in patients with pulmonary hypertension: A randomised placebo‐controlled study. Lancet 358: 1119‐1123, 2001.
 113.Checchia PA, Bronicki RA, Muenzer JT, Dixon D, Raithel S, Gandhi SK, Huddleston CB. Nitric oxide delivery during cardiopulmonary bypass reduces postoperative morbidity in children—a randomized trial. J Thorac Cardiovasc Surg 146: 530‐536, 2013.
 114.Check J, Gotteiner N, Liu X, Su E, Porta N, Steinhorn R, Mestan KK. Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia. J Perinatol 33: 553‐557, 2013.
 115.Cheng Y, Tung CK, Chung AKK, Liu WW, Huang D, Chan PH, Lam M, Chan WC, Siu CW, Hai JJ. Screening of pulmonary hypertension in methamphetamine abusers (SOPHMA): Rationale and design of a multicentre, cross‐sectional study. BMJ Open 9: e027193, 2019.
 116.Chiu JS, Zuckerman WA, Turner ME, Richmond ME, Kerstein D, Krishnan U, Torres A, Vincent JA, Rosenzweig EB. Balloon atrial septostomy in pulmonary arterial hypertension: Effect on survival and associated outcomes. J Heart Lung Transplant 34: 376‐380, 2015.
 117.Chiu PP. New insights into congenital diaphragmatic hernia—A surgeon's introduction to CDH animal models. Front Pediatr 2: 36, 2014.
 118.Cho YJ, Han JY, Lee SG, Jeon BT, Choi WS, Hwang YS, Roh GS, Lee JD. Temporal changes of angiopoietins and Tie2 expression in rat lungs after monocrotaline‐induced pulmonary hypertension. Comp Med 59: 350‐356, 2009.
 119.Christou H, Yoshida A, Arthur V, Morita T, Kourembanas S. Increased vascular endothelial growth factor production in the lungs of rats with hypoxia‐induced pulmonary hypertension. Am J Respir Cell Mol Biol 18: 768‐776, 1998.
 120.Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, Roy BJ, Keszler M, Kinsella JP. Low‐dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. N Engl J Med 342: 469‐474, 2000.
 121.Clozel M, Breu V, Gray GA, Loffler BM. In vivo pharmacology of Ro 46‐2005, the first synthetic nonpeptide endothelin receptor antagonist: Implications for endothelin physiology. J Cardiovasc Pharmacol 22 (Suppl 8): S377‐S379, 1993.
 122.Cochius‐den Otter S, Schaible T, Greenough A, van Heijst A, Patel N, Allegaert K, van Rosmalen J, Tibboel D, Consortium CE. The CoDiNOS trial protocol: An international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia. BMJ Open 9: e032122, 2019.
 123.Cohen JL, Nees SN, Valencia GA, Rosenzweig EB, Krishnan US. Sildenafil use in children with pulmonary hypertension. J Pediatr 205: 29‐34 e21, 2019.
 124.Colvin KL, Dufva MJ, Delaney RP, Ivy DD, Stenmark KR, Yeager ME. Biomarkers for pediatric pulmonary arterial hypertension ‐ A call to collaborate. Front Pediatr 2: 7, 2014.
 125.Coppola CP, Gosche JR. Oxygen‐induced vasodilation is blunted in pulmonary arterioles from fetal rats with nitrofen‐induced congenital diaphragmatic hernia. J Pediatr Surg 36: 593‐597, 2001.
 126.Cornfield DN, Maynard RC, deRegnier RA, Guiang SF 3rd, Barbato JE, Milla CE. Randomized, controlled trial of low‐dose inhaled nitric oxide in the treatment of term and near‐term infants with respiratory failure and pulmonary hypertension. Pediatrics 104: 1089‐1094, 1999.
 127.Corsico AG, D'Armini AM, Cerveri I, Klersy C, Ansaldo E, Niniano R, Gatto E, Monterosso C, Morsolini M, Nicolardi S, Tramontin C, Pozzi E, Vigano M. Long‐term outcome after pulmonary endarterectomy. Am J Respir Crit Care Med 178: 419‐424, 2008.
 128.Cowan KN, Heilbut A, Humpl T, Lam C, Ito S, Rabinovitch M. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat Med 6: 698‐702, 2000.
 129.Cracowski JL, Cracowski C, Bessard G, Pepin JL, Bessard J, Schwebel C, Stanke‐Labesque F, Pison C. Increased lipid peroxidation in patients with pulmonary hypertension. Am J Respir Crit Care Med 164: 1038‐1042, 2001.
 130.Critser PJ, Higano NS, Tkach JA, Olson ES, Spielberg DR, Kingma PS, Fleck RJ, Lang SM, Moore RA, Taylor MD, Woods JC. Cardiac magnetic resonance imaging evaluation of neonatal bronchopulmonary dysplasia‐associated pulmonary hypertension. Am J Respir Crit Care Med 201: 73‐82, 2020.
 131.Crossno JT Jr, Garat CV, Reusch JE, Morris KG, Dempsey EC, McMurtry IF, Stenmark KR, Klemm DJ. Rosiglitazone attenuates hypoxia‐induced pulmonary arterial remodeling. Am J Physiol Lung Cell Mol Physiol 292: L885‐L897, 2007.
 132.Daftari B, Alejos JC, Perens G. Initial experience with sildenafil, bosentan, and nitric oxide for pediatric cardiomyopathy patients with elevated pulmonary vascular resistance before and after orthotopic heart transplantation. J Transplant 2010: 656984, 2010.
 133.Dani C, Bertini G, Pezzati M, Filippi L, Cecchi A, Rubaltelli FF. Inhaled nitric oxide in very preterm infants with severe respiratory distress syndrome. Acta Paediatr 95: 1116‐1123, 2006.
 134.Darlow BA, Marschner SL, Donoghoe M, Battin MR, Broadbent RS, Elder MJ, Hewson MP, Meyer MP, Ghadge A, Graham P, McNeill NJ, Kuschel CA, Tarnow‐Mordi WO, Benefits of Oxygen Saturation Targeting‐New Zealand Collaborative Group. Randomized controlled trial of oxygen saturation targets in very preterm infants: Two year outcomes. J Pediatr 165: 30‐35 e32, 2014.
 135.Davidson D, Barefield ES, Kattwinkel J, Dudell G, Damask M, Straube R, Rhines J, Chang CT. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: A randomized, double‐masked, placebo‐controlled, dose‐response, multicenter study. The I‐NO/PPHN Study Group. Pediatrics 101: 325‐334, 1998.
 136.Davidson D, Barefield ES, Kattwinkel J, Dudell G, Damask M, Straube R, Rhines J, Chang CT. Safety of withdrawing inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn. Pediatrics 104: 231‐236, 1999.
 137.Day RW, Lynch JM, White KS, Ward RM. Acute response to inhaled nitric oxide in newborns with respiratory failure and pulmonary hypertension. Pediatrics 98: 698‐705, 1996.
 138.de Man FS, Tu L, Handoko ML, Rain S, Ruiter G, Francois C, Schalij I, Dorfmuller P, Simonneau G, Fadel E, Perros F, Boonstra A, Postmus PE, van der Velden J, Vonk‐Noordegraaf A, Humbert M, Eddahibi S, Guignabert C. Dysregulated renin‐angiotensin‐aldosterone system contributes to pulmonary arterial hypertension. Am J Respir Crit Care Med 186: 780‐789, 2012.
 139.De Paepe ME, Mao Q, Powell J, Rubin SE, DeKoninck P, Appel N, Dixon M, Gundogan F. Growth of pulmonary microvasculature in ventilated preterm infants. Am J Respir Crit Care Med 173: 204‐211, 2006.
 140.Del Cerro MJ, Moledina S, Haworth SG, Ivy D, Al Dabbagh M, Banjar H, Diaz G, Heath‐Freudenthal A, Galal AN, Humpl T, Kulkarni S, Lopes A, Mocumbi AO, Puri GD, Rossouw B, Harikrishnan S, Saxena A, Udo P, Caicedo L, Tamimi O, Adatia I. Cardiac catheterization in children with pulmonary hypertensive vascular disease: Consensus statement from the Pulmonary Vascular Research Institute. Pediatric and Congenital Heart Disease Task Forces. Pulm Circ 6: 118‐125, 2016.
 141.del Cerro MJ, Sabate Rotes A, Carton A, Deiros L, Bret M, Cordeiro M, Verdu C, Barrios MI, Albajara L, Gutierrez‐Larraya F. Pulmonary hypertension in bronchopulmonary dysplasia: Clinical findings, cardiovascular anomalies and outcomes. Pediatr Pulmonol 49: 49‐59, 2014.
 142.del Cerro Marin MJ, Sabate Rotes A, Rodriguez Ogando A, Mendoza Soto A, Quero Jimenez M, Gavilan Camacho JL, Raposo Sonnenfeld I, Moya Bonora A, Albert Brotons DC, Moreno Galdo A, Investigators R. Assessing pulmonary hypertensive vascular disease in childhood. Data from the Spanish registry. Am J Respir Crit Care Med 190: 1421‐1429, 2014.
 143.Delaney C, Cornfield DN. Risk factors for persistent pulmonary hypertension of the newborn. Pulm Circ 2: 15‐20, 2012.
 144.Delaney C, Gien J, Grover TR, Roe G, Abman SH. Pulmonary vascular effects of serotonin and selective serotonin reuptake inhibitors in the late‐gestation ovine fetus. Am J Physiol Lung Cell Mol Physiol 301: L937‐L944, 2011.
 145.Delaney C, Gien J, Roe G, Isenberg N, Kailey J, Abman SH. Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn. Am J Physiol Lung Cell Mol Physiol 304: L894‐L901, 2013.
 146.Delhaas T, Koeken Y, Latus H, Apitz C, Schranz D. Potts shunt to be preferred above atrial septostomy in pediatric pulmonary arterial hypertension patients: A modeling study. Front Physiol 9: 1252, 2018.
 147.Deng Z, Morse JH, Slager SL, Cuervo N, Moore KJ, Venetos G, Kalachikov S, Cayanis E, Fischer SG, Barst RJ, Hodge SE, Knowles JA. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor‐II gene. Am J Hum Genet 67: 737‐744, 2000.
 148.Dennis KE, Aschner JL, Milatovic D, Schmidt JW, Aschner M, Kaplowitz MR, Zhang Y, Fike CD. NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia‐induced pulmonary hypertension in newborn piglets. Am J Physiol Lung Cell Mol Physiol 297: L596‐L607, 2009.
 149.Dhariwal AK, Bavdekar SB. Sildenafil in pediatric pulmonary arterial hypertension. J Postgrad Med 61: 181‐192, 2015.
 150.Dhawan RT, Gopalan D, Howard L, Vicente A, Park M, Manalan K, Wallner I, Marsden P, Dave S, Branley H, Russell G, Dharmarajah N, Kon OM. Beyond the clot: Perfusion imaging of the pulmonary vasculature after COVID‐19. Lancet Respir Med, 2020.
 151.Diller GP, Dimopoulos K, Broberg CS, Kaya MG, Naghotra US, Uebing A, Harries C, Goktekin O, Gibbs JS, Gatzoulis MA. Presentation, survival prospects, and predictors of death in Eisenmenger syndrome: A combined retrospective and case‐control study. Eur Heart J 27: 1737‐1742, 2006.
 152.Ding XF, Liang HY, Yuan B, Li LF, Wang T, Kan QC, Wang LX, Sun TW. Efficacy of stem cell therapy for pulmonary arterial hypertension: A systematic review and meta‐analysis of preclinical studies. Stem Cell Res Ther 10: 55, 2019.
 153.Do e Z, Fukumoto Y, Takaki A, Tawara S, Ohashi J, Nakano M, Tada T, Saji K, Sugimura K, Fujita H, Hoshikawa Y, Nawata J, Kondo T, Shimokawa H. Evidence for Rho‐kinase activation in patients with pulmonary arterial hypertension. Circ J 73: 1731‐1739, 2009.
 154.Donda K, Zambrano R, Moon Y, Percival J, Vaidya R, Dapaah‐Siakwan F, Luo S, Duncan MR, Bao Y, Wang L, Qin L, Benny M, Young K, Wu S. Riociguat prevents hyperoxia‐induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth. PLoS One 13: e0199927, 2018.
 155.Doran AK, Ivy DD, Barst RJ, Hill N, Murali S, Benza RL, Scientific Leadership Council of the Pulmonary Hypertension A. Guidelines for the prevention of central venous catheter‐related blood stream infections with prostanoid therapy for pulmonary arterial hypertension. Int J Clin Pract Suppl 5‐9, 2008.
 156.Douwes JM, Hegeman AK, van der Krieke MB, Roofthooft MT, Hillege HL, Berger RM. Six‐minute walking distance and decrease in oxygen saturation during the six‐minute walk test in pediatric pulmonary arterial hypertension. Int J Cardiol 202: 34‐39, 2016.
 157.Douwes JM, Humpl T, Bonnet D, Beghetti M, Ivy DD, Berger RM, Investigators T. Acute vasodilator response in pediatric pulmonary arterial hypertension: current clinical practice from the TOPP registry. J Am Coll Cardiol 67: 1312‐1323, 2016.
 158.Douwes JM, Roofthooft MT, Bartelds B, Talsma MD, Hillege HL, Berger RM. Pulsatile haemodynamic parameters are predictors of survival in paediatric pulmonary arterial hypertension. Int J Cardiol 168: 1370‐1377, 2013.
 159.Du Y, Fu J, Yao L, Qiao L, Liu N, Xing Y, Xue X. Altered expression of PPARgamma and TRPC in neonatal rats with persistent pulmonary hypertension. Mol Med Rep 16: 1117‐1124, 2017.
 160.Dupuis J. Endothelin‐receptor antagonists in pulmonary hypertension. Lancet 358: 1113‐1114, 2001.
 161.Durmowicz AG, Stenmark KR. Mechanisms of structural remodeling in chronic pulmonary hypertension. Pediatr Rev 20: e91‐e102, 1999.
 162.Eddahibi S, Guignabert C, Barlier‐Mur AM, Dewachter L, Fadel E, Dartevelle P, Humbert M, Simonneau G, Hanoun N, Saurini F, Hamon M, Adnot S. Cross talk between endothelial and smooth muscle cells in pulmonary hypertension: Critical role for serotonin‐induced smooth muscle hyperplasia. Circulation 113: 1857‐1864, 2006.
 163.Esch JJ, Shah PB, Cockrill BA, Farber HW, Landzberg MJ, Mehra MR, Mullen MP, Opotowsky AR, Waxman AB, Lock JE, Marshall AC. Transcatheter Potts shunt creation in patients with severe pulmonary arterial hypertension: Initial clinical experience. J Heart Lung Transplant 32: 381‐387, 2013.
 164.Etienne‐Manneville S, Hall A. Rho GTPases in cell biology. Nature 420: 629‐635, 2002.
 165.Evans JD, Girerd B, Montani D, Wang XJ, Galie N, Austin ED, Elliott G, Asano K, Grunig E, Yan Y, Jing ZC, Manes A, Palazzini M, Wheeler LA, Nakayama I, Satoh T, Eichstaedt C, Hinderhofer K, Wolf M, Rosenzweig EB, Chung WK, Soubrier F, Simonneau G, Sitbon O, Graf S, Kaptoge S, Di Angelantonio E, Humbert M, Morrell NW. BMPR2 mutations and survival in pulmonary arterial hypertension: An individual participant data meta‐analysis. Lancet Respir Med 4: 129‐137, 2016.
 166.Eyries M, Montani D, Girerd B, Perret C, Leroy A, Lonjou C, Chelghoum N, Coulet F, Bonnet D, Dorfmuller P, Fadel E, Sitbon O, Simonneau G, Tregouet DA, Humbert M, Soubrier F. EIF2AK4 mutations cause pulmonary veno‐occlusive disease, a recessive form of pulmonary hypertension. Nat Genet 46: 65‐69, 2014.
 167.Ezekian JE, Hill KD. Management of pulmonary arterial hypertension in the pediatric patient. Curr Cardiol Rep 21: 162, 2019.
 168.Fagan KA, Oka M, Bauer NR, Gebb SA, Ivy DD, Morris KG, McMurtry IF. Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho‐kinase. Am J Physiol Lung Cell Mol Physiol 287: L656‐L664, 2004.
 169.Fagard R, Conway J. Measurement of cardiac output: Fick principle using catheterization. Eur Heart J 11 (Suppl I): 1‐5, 1990.
 170.Fantozzi I, Zhang S, Platoshyn O, Remillard CV, Cowling RT, Yuan JX. Hypoxia increases AP‐1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 285: L1233‐L1245, 2003.
 171.Farhat N, Lador F, Beghetti M. Diagnosis and treatment of pediatric pulmonary arterial hypertension. Expert Rev Cardiovasc Ther 17: 161‐175, 2019.
 172.Farkas L, Farkas D, Ask K, Moller A, Gauldie J, Margetts P, Inman M, Kolb M. VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats. J Clin Invest 119: 1298‐1311, 2009.
 173.Farrow KN, Groh BS, Schumacker PT, Lakshminrusimha S, Czech L, Gugino SF, Russell JA, Steinhorn RH. Hyperoxia increases phosphodiesterase 5 expression and activity in ovine fetal pulmonary artery smooth muscle cells. Circ Res 102: 226‐233, 2008.
 174.Farrow KN, Lakshminrusimha S, Reda WJ, Wedgwood S, Czech L, Gugino SF, Davis JM, Russell JA, Steinhorn RH. Superoxide dismutase restores eNOS expression and function in resistance pulmonary arteries from neonatal lambs with persistent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 295: L979‐L987, 2008.
 175.Farrow KN, Lee KJ, Perez M, Schriewer JM, Wedgwood S, Lakshminrusimha S, Smith CL, Steinhorn RH, Schumacker PT. Brief hyperoxia increases mitochondrial oxidation and increases phosphodiesterase 5 activity in fetal pulmonary artery smooth muscle cells. Antioxid Redox Signal 17: 460‐470, 2012.
 176.Farrow KN, Wedgwood S, Lee KJ, Czech L, Gugino SF, Lakshminrusimha S, Schumacker PT, Steinhorn RH. Mitochondrial oxidant stress increases PDE5 activity in persistent pulmonary hypertension of the newborn. Respir Physiol Neurobiol 174: 272‐281, 2010.
 177.Fedullo PF, Auger WR, Channick RN, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. Clin Chest Med 22: 561‐581, 2001.
 178.Ferdman DJ, Rosenzweig EB, Zuckerman WA, Krishnan U. Subcutaneous treprostinil for pulmonary hypertension in chronic lung disease of infancy. Pediatrics 134: e274‐e278, 2014.
 179.Fessel JP, Flynn CR, Robinson LJ, Penner NL, Gladson S, Kang CJ, Wasserman DH, Hemnes AR, West JD. Hyperoxia synergizes with mutant bone morphogenic protein receptor 2 to cause metabolic stress, oxidant injury, and pulmonary hypertension. Am J Respir Cell Mol Biol 49: 778‐787, 2013.
 180.Field D, Elbourne D, Hardy P, Fenton AC, Ahluwalia J, Halliday HL, Subhedar N, Heinonen K, Aikio O, Grieve R, Truesdale A, Tomlin K, Normand C, Stocks J, Group ITC. Neonatal ventilation with inhaled nitric oxide vs. ventilatory support without inhaled nitric oxide for infants with severe respiratory failure born at or near term: The INNOVO multicentre randomised controlled trial. Neonatology 91: 73‐82, 2007.
 181.Fike CD, Slaughter JC, Kaplowitz MR, Zhang Y, Aschner JL. Reactive oxygen species from NADPH oxidase contribute to altered pulmonary vascular responses in piglets with chronic hypoxia‐induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 295: L881‐L888, 2008.
 182.Foglia EE, Carper B, Gantz M, DeMauro SB, Lakshminrusimha S, Walsh M, Schmidt B, Eunice Kennedy Shriver National Institute of Child H, and Human Development Neonatal Research N. Association between policy changes for oxygen saturation alarm settings and neonatal morbidity and mortality in infants born very preterm. J Pediatr 209: 17‐22. e12, 2019.
 183.Fraisse A, Butrous G, Taylor MB, Oakes M, Dilleen M, Wessel DL. Intravenous sildenafil for postoperative pulmonary hypertension in children with congenital heart disease. Intensive Care Med 37: 502‐509, 2011.
 184.Frank BS, Ivy DD. Diagnosis, evaluation and treatment of pulmonary arterial hypertension in children. Children (Basel) 5: 44, 2018.
 185.Frank BS, Schafer M, Grenolds A, Ivy DD, Abman SH, Darst JR. Acute vasoreactivity testing during cardiac catheterization of neonates with bronchopulmonary dysplasia‐associated pulmonary hypertension. J Pediatr 208: 127‐133, 2019.
 186.Fredenburgh LE, Liang OD, Macias AA, Polte TR, Liu X, Riascos DF, Chung SW, Schissel SL, Ingber DE, Mitsialis SA, Kourembanas S, Perrella MA. Absence of cyclooxygenase‐2 exacerbates hypoxia‐induced pulmonary hypertension and enhances contractility of vascular smooth muscle cells. Circulation 117: 2114‐2122, 2008.
 187.Fredriksson L, Li H, Eriksson U. The PDGF family: Four gene products form five dimeric isoforms. Cytokine Growth Factor Rev 15: 197‐204, 2004.
 188.Fujiwara M, Yagi H, Matsuoka R, Akimoto K, Furutani M, Imamura S, Uehara R, Nakayama T, Takao A, Nakazawa M, Saji T. Implications of mutations of activin receptor‐like kinase 1 gene (ALK1) in addition to bone morphogenetic protein receptor II gene (BMPR2) in children with pulmonary arterial hypertension. Circ J 72: 127‐133, 2008.
 189.Fukumoto Y, Yamada N, Matsubara H, Mizoguchi M, Uchino K, Yao A, Kihara Y, Kawano M, Watanabe H, Takeda Y, Adachi T, Osanai S, Tanabe N, Inoue T, Kubo A, Ota Y, Fukuda K, Nakano T, Shimokawa H. Double‐blind, placebo‐controlled clinical trial with a rho‐kinase inhibitor in pulmonary arterial hypertension. Circ J 77: 2619‐2625, 2013.
 190.Fuloria M, Aschner JL. Persistent pulmonary hypertension of the newborn. Semin Fetal Neonatal Med 22: 220‐226, 2017.
 191.Galie N, Manes A, Branzi A. The endothelin system in pulmonary arterial hypertension. Cardiovasc Res 61: 227‐237, 2004.
 192.Galie N, McLaughlin VV, Rubin LJ, Simonneau G. An overview of the 6th World Symposium on Pulmonary Hypertension. Eur Respir J 53: 1802148, 2019.
 193.Galie N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, Badesch DB, McGoon MD, McLaughlin VV, Roecker EB, Gerber MJ, Dufton C, Wiens BL, Rubin LJ, Ambrisentan in Pulmonary Arterial Hypertension RD‐BP‐CMESG. Ambrisentan for the treatment of pulmonary arterial hypertension: Results of the ambrisentan in pulmonary arterial hypertension, randomized, double‐blind, placebo‐controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation 117: 3010‐3019, 2008.
 194.Galie N, Torbicki A, Barst R, Dartevelle P, Haworth S, Higenbottam T, Olschewski H, Peacock A, Pietra G, Rubin LJ, Simonneau G, Priori SG, Garcia MA, Blanc JJ, Budaj A, Cowie M, Dean V, Deckers J, Burgos EF, Lekakis J, Lindahl B, Mazzotta G, McGregor K, Morais J, Oto A, Smiseth OA, Barbera JA, Gibbs S, Hoeper M, Humbert M, Naeije R, Pepke‐Zaba J, Task F. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The task force on diagnosis and treatment of pulmonary arterial hypertension of the European Society of Cardiology. Eur Heart J 25: 2243, 2004‐2278.
 195.Gan C, Lankhaar JW, Marcus JT, Westerhof N, Marques KM, Bronzwaer JG, Boonstra A, Postmus PE, Vonk‐Noordegraaf A. Impaired left ventricular filling due to right‐to‐left ventricular interaction in patients with pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 290: H1528‐H1533, 2006.
 196.Gan CT, Holverda S, Marcus JT, Paulus WJ, Marques KM, Bronzwaer JG, Twisk JW, Boonstra A, Postmus PE, Vonk‐Noordegraaf A. Right ventricular diastolic dysfunction and the acute effects of sildenafil in pulmonary hypertension patients. Chest 132: 11‐17, 2007.
 197.Gao Y, Chen T, Raj JU. Endothelial and smooth muscle cell interactions in the pathobiology of pulmonary hypertension. Am J Respir Cell Mol Biol 54: 451‐460, 2016.
 198.Garofano RP, Barst RJ. Exercise testing in children with primary pulmonary hypertension. Pediatr Cardiol 20: 61‐64; discussion 65, 1999.
 199.Gaynor JW, Bull C, Sullivan ID, Armstrong BE, Deanfield JE, Taylor JF, Rees PG, Ungerleider RM, de Leval MR, Stark J, et al. Late outcome of survivors of intervention for neonatal aortic valve stenosis. Ann Thorac Surg 60: 122‐125; discussion 125‐126, 1995.
 200.Gentles TL, Gauvreau K, Mayer JE Jr, Fishberger SB, Burnett J, Colan SD, Newburger JW, Wernovsky G. Functional outcome after the Fontan operation: Factors influencing late morbidity. J Thorac Cardiovasc Surg 114: 392‐403; discussion 404‐395, 1997.
 201.George J, D'Armiento J. Transgenic expression of human matrix metalloproteinase‐9 augments monocrotaline‐induced pulmonary arterial hypertension in mice. J Hypertens 29: 299‐308, 2011.
 202.Gerthoffer WT. Mechanisms of vascular smooth muscle cell migration. Circ Res 100: 607‐621, 2007.
 203.Ghofrani HA, D'Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, Mayer E, Simonneau G, Wilkins MR, Fritsch A, Neuser D, Weimann G, Wang C, Group C‐S. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 369: 319‐329, 2013.
 204.Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, Keogh AM, Langleben D, Kilama MO, Fritsch A, Neuser D, Rubin LJ, Group P‐S. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 369: 330‐340, 2013.
 205.Ghofrani HA, Osterloh IH, Grimminger F. Sildenafil: From angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov 5: 689‐702, 2006.
 206.Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 333: 214‐221, 1995.
 207.Gien J, Kinsella JP. Management of pulmonary hypertension in infants with congenital diaphragmatic hernia. J Perinatol 36 (Suppl 2): S28‐S31, 2016.
 208.Gien J, Seedorf GJ, Balasubramaniam V, Markham N, Abman SH. Intrauterine pulmonary hypertension impairs angiogenesis in vitro: Role of vascular endothelial growth factor nitric oxide signaling. Am J Respir Crit Care Med 176: 1146‐1153, 2007.
 209.Gien J, Tseng N, Seedorf G, Roe G, Abman SH. Endothelin‐1 impairs angiogenesis in vitro through Rho‐kinase activation after chronic intrauterine pulmonary hypertension in fetal sheep. Pediatr Res 73: 252‐262, 2013.
 210.Giordano R, Palma G, Poli V, Palumbo S, Russolillo V, Cioffi S, Mucerino M, Mannacio VA, Vosa C. First experience with sildenafil after Fontan operation: Short‐term outcomes. J Cardiovasc Med (Hagerstown) 16: 552‐555, 2015.
 211.Girerd B, Montani D, Coulet F, Sztrymf B, Yaici A, Jais X, Tregouet D, Reis A, Drouin‐Garraud V, Fraisse A, Sitbon O, O'Callaghan DS, Simonneau G, Soubrier F, Humbert M. Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation. Am J Respir Crit Care Med 181: 851‐861, 2010.
 212.Goldberg DJ, French B, McBride MG, Marino BS, Mirarchi N, Hanna BD, Wernovsky G, Paridon SM, Rychik J. Impact of oral sildenafil on exercise performance in children and young adults after the fontan operation: A randomized, double‐blind, placebo‐controlled, crossover trial. Circulation 123: 1185‐1193, 2011.
 213.Goldberg DJ, Zak V, Goldstein BH, Chen S, Hamstra MS, Radojewski EA, Maunsell E, Mital S, Menon SC, Schumacher KR, Payne RM, Stylianou M, Kaltman JR, deVries TM, Yeager JL, Paridon SM, Pediatric Heart Network I. Results of a phase I/II multi‐center investigation of udenafil in adolescents after fontan palliation. Am Heart J 188: 42‐52, 2017.
 214.Goldberg DJ, Zak V, Goldstein BH, Schumacher KR, Rhodes J, Penny DJ, Petit CJ, Ginde S, Menon SC, Kim SH, Kim GB, Nowlen TT, DiMaria MV, Frischhertz BP, Wagner JB, McHugh KE, McCrindle BW, Shillingford AJ, Sabati AA, Yetman AT, John AS, Richmond ME, Files MD, Payne RM, Mackie AS, Davis CK, Shahanavaz S, Hill KD, Garg R, Jacobs JP, Hamstra MS, Woyciechowski S, Rathge KA, MG MB, Frommelt PC, Russell MW, Urbina EM, Yeager JL, Pemberton VL, Stylianou MP, Pearson GD, Paridon SM, Pediatric Heart Network I. Results of the FUEL trial. Circulation 141: 641‐651, 2020.
 215.Goldstein I, Lue TF, Padma‐Nathan H, Rosen RC, Steers WD, Wicker PA. Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N Engl J Med 338: 1397‐1404, 1998.
 216.Gomberg‐Maitland M, Tapson VF, Benza RL, McLaughlin VV, Krichman A, Widlitz AC, Barst RJ. Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med 172: 1586‐1589, 2005.
 217.Gonzalez A, Fabres J, D'Apremont I, Urcelay G, Avaca M, Gandolfi C, Kattan J. Randomized controlled trial of early compared with delayed use of inhaled nitric oxide in newborns with a moderate respiratory failure and pulmonary hypertension. J Perinatol 30: 420‐424, 2010.
 218.Good RB, Gilbane AJ, Trinder SL, Denton CP, Coghlan G, Abraham DJ, Holmes AM. Endothelial to mesenchymal transition contributes to endothelial dysfunction in pulmonary arterial hypertension. Am J Pathol 185: 1850‐1858, 2015.
 219.Gorbachevsky SV, Shmalts AA, Barishnikova IY, Zaets SB. Potts shunt in children with pulmonary arterial hypertension: Institutional experience. Interact Cardiovasc Thorac Surg 25: 595‐599, 2017.
 220.Gorenflo M, Vogel M, Obladen M. Pulmonary vascular changes in bronchopulmonary dysplasia: A clinicopathologic correlation in short‐ and long‐term survivors. Pediatr Pathol 11: 851‐866, 1991.
 221.Graham BB, Kumar R, Mickael C, Kassa B, Koyanagi D, Sanders L, Zhang L, Perez M, Hernandez‐Saavedra D, Valencia C, Dixon K, Harral J, Loomis Z, Irwin D, Nemkov T, D'Alessandro A, Stenmark KR, Tuder RM. Vascular adaptation of the right ventricle in experimental pulmonary hypertension. Am J Respir Cell Mol Biol 59: 479‐489, 2018.
 222.Green DE, Murphy TC, Kang BY, Searles CD, Hart CM. PPARgamma ligands attenuate hypoxia‐induced proliferation in human pulmonary artery smooth muscle cells through modulation of MicroRNA‐21. PLoS One 10: e0133391, 2015.
 223.Green DE, Sutliff RL, Hart CM. Is peroxisome proliferator‐activated receptor gamma (PPARgamma) a therapeutic target for the treatment of pulmonary hypertension? Pulm Circ 1: 33‐47, 2011.
 224.Gridley T. Notch signaling in vascular development and physiology. Development 134: 2709‐2718, 2007.
 225.Grosse‐Wortmann L, Al‐Otay A, Yoo SJ. Aortopulmonary collaterals after bidirectional cavopulmonary connection or Fontan completion: Quantification with MRI. Circ Cardiovasc Imaging 2: 219‐225, 2009.
 226.Grothues F, Moon JC, Bellenger NG, Smith GS, Klein HU, Pennell DJ. Interstudy reproducibility of right ventricular volumes, function, and mass with cardiovascular magnetic resonance. Am Heart J 147: 218‐223, 2004.
 227.Grunig E, Benjamin N, Kruger U, Kaemmerer H, Harutyunova S, Olsson KM, Ulrich S, Gerhardt F, Neurohr C, Sablotzki A, Halank M, Marra AM, Kabitz HJ, Thimm G, Fliegel KG, Klose H. General measures and supportive therapy for pulmonary arterial hypertension: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol 272S: 30‐36, 2018.
 228.Guo L, Cui Y, Pharis S, Walsh M, Atallah J, Tan MW, Rutledge J, Coe JY, Adatia I. Measurement of oxygen consumption in children undergoing cardiac catheterization: Comparison between mass spectrometry and the breath‐by‐breath method. Pediatr Cardiol 35: 798‐802, 2014.
 229.Gupta VS, Harting MT. Congenital diaphragmatic hernia‐associated pulmonary hypertension. Semin Perinatol 44: 151167, 2020.
 230.Haddad IY, Ischiropoulos H, Holm BA, Beckman JS, Baker JR, Matalon S. Mechanisms of peroxynitrite‐induced injury to pulmonary surfactants. Am J Physiol 265: L555‐L564, 1993.
 231.Hammerstingl C, Schueler R, Bors L, Momcilovic D, Pabst S, Nickenig G, Skowasch D. Diagnostic value of echocardiography in the diagnosis of pulmonary hypertension. PLoS One 7: e38519, 2012.
 232.Hampl V, Herget J. Role of nitric oxide in the pathogenesis of chronic pulmonary hypertension. Physiol Rev 80: 1337‐1372, 2000.
 233.Hansmann G. Pulmonary hypertension in infants, children, and young adults. J Am Coll Cardiol 69: 2551‐2569, 2017.
 234.Hansmann G, de Jesus Perez VA, Alastalo TP, Alvira CM, Guignabert C, Bekker JM, Schellong S, Urashima T, Wang L, Morrell NW, Rabinovitch M. An antiproliferative BMP‐2/PPARgamma/apoE axis in human and murine SMCs and its role in pulmonary hypertension. J Clin Invest 118: 1846‐1857, 2008.
 235.Hansmann G, Koestenberger M, Alastalo TP, Apitz C, Austin ED, Bonnet D, Budts W, D'Alto M, Gatzoulis MA, Hasan BS, Kozlik‐Feldmann R, Kumar RK, Lammers AE, Latus H, Michel‐Behnke I, Miera O, Morrell NW, Pieles G, Quandt D, Sallmon H, Schranz D, Tran‐Lundmark K, Tulloh RMR, Warnecke G, Wahlander H, Weber SC, Zartner P. 2019 updated consensus statement on the diagnosis and treatment of pediatric pulmonary hypertension: The European Pediatric Pulmonary Vascular Disease Network (EPPVDN), endorsed by AEPC, ESPR and ISHLT. J Heart Lung Transplant 38: 879‐901, 2019.
 236.Hao YJ, Jiang X, Zhou W, Wang Y, Gao L, Wang Y, Li GT, Hong T, Huo Y, Jing ZC, Zhang ZL. Connective tissue disease‐associated pulmonary arterial hypertension in Chinese patients. Eur Respir J 44: 963‐972, 2014.
 237.Hardegree EL, Sachdev A, Villarraga HR, Frantz RP, McGoon MD, Kushwaha SS, Hsiao JF, McCully RB, Oh JK, Pellikka PA, Kane GC. Role of serial quantitative assessment of right ventricular function by strain in pulmonary arterial hypertension. Am J Cardiol 111: 143‐148, 2013.
 238.Harrison RE, Berger R, Haworth SG, Tulloh R, Mache CJ, Morrell NW, Aldred MA, Trembath RC. Transforming growth factor‐beta receptor mutations and pulmonary arterial hypertension in childhood. Circulation 111: 435‐441, 2005.
 239.Harting MT. Congenital diaphragmatic hernia‐associated pulmonary hypertension. Semin Pediatr Surg 26: 147‐153, 2017.
 240.Hascoet JM, Fresson J, Claris O, Hamon I, Lombet J, Liska A, Cantagrel S, Al Hosri J, Thiriez G, Valdes V, Vittu G, Egreteau L, Henrot A, Buchweiller MC, Onody P. The safety and efficacy of nitric oxide therapy in premature infants. J Pediatr 146: 318‐323, 2005.
 241.Haworth SG, Reid L. Quantitative structural study of pulmonary circulation in the newborn with aortic atresia, stenosis, or coarctation. Thorax 32: 121‐128, 1977.
 242.Hayashi S, Morishita R, Nakamura S, Yamamoto K, Moriguchi A, Nagano T, Taiji M, Noguchi H, Matsumoto K, Nakamura T, Higaki J, Ogihara T. Potential role of hepatocyte growth factor, a novel angiogenic growth factor, in peripheral arterial disease: Downregulation of HGF in response to hypoxia in vascular cells. Circulation 100: II301‐II308, 1999.
 243.Heching HJ, Turner M, Farkouh‐Karoleski C, Krishnan U. Pulmonary vein stenosis and necrotising enterocolitis: Is there a possible link with necrotising enterocolitis? Arch Dis Child Fetal Neonatal Ed 99: F282‐F285, 2014.
 244.Heilman RP, Lagoski MB, Lee KJ, Taylor JM, Kim GA, Berkelhamer SK, Steinhorn RH, Farrow KN. Right ventricular cyclic nucleotide signaling is decreased in hyperoxia‐induced pulmonary hypertension in neonatal mice. Am J Physiol Heart Circ Physiol 308: H1575‐H1582, 2015.
 245.Hernandez‐Diaz S, Van Marter LJ, Werler MM, Louik C, Mitchell AA. Risk factors for persistent pulmonary hypertension of the newborn. Pediatrics 120: e272‐e282, 2007.
 246.Hilgendorff A, Apitz C, Bonnet D, Hansmann G. Pulmonary hypertension associated with acute or chronic lung diseases in the preterm and term neonate and infant. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 102 (Suppl 2): ii49‐ii56, 2016.
 247.Hill KD, Tunks RD, Barker PC, Benjamin DK Jr, Cohen‐Wolkowiez M, Fleming GA, Laughon M, Li JS. Sildenafil exposure and hemodynamic effect after stage II single‐ventricle surgery. Pediatr Crit Care Med 14: 593‐600, 2013.
 248.Hirata Y, Emori T, Eguchi S, Kanno K, Imai T, Ohta K, Marumo F. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J Clin Invest 91: 1367‐1373, 1993.
 249.Hirenallur SD, Haworth ST, Leming JT, Chang J, Hernandez G, Gordon JB, Rusch NJ. Upregulation of vascular calcium channels in neonatal piglets with hypoxia‐induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 295: L915‐L924, 2008.
 250.Hislop AA, Moledina S, Foster H, Schulze‐Neick I, Haworth SG. Long‐term efficacy of bosentan in treatment of pulmonary arterial hypertension in children. Eur Respir J 38: 70‐77, 2011.
 251.Ho JJ, Man HS, Marsden PA. Nitric oxide signaling in hypoxia. J Mol Med (Berl) 90: 217‐231, 2012.
 252.Hoffman JI. Pulmonary vascular resistance and viscosity: The forgotten factor. Pediatr Cardiol 32: 557‐561, 2011.
 253.Hoffmann J, Marsh LM, Pieper M, Stacher E, Ghanim B, Kovacs G, Konig P, Wilkens H, Haitchi HM, Hoefler G, Klepetko W, Olschewski H, Olschewski A, Kwapiszewska G. Compartment‐specific expression of collagens and their processing enzymes in intrapulmonary arteries of IPAH patients. Am J Physiol Lung Cell Mol Physiol 308: L1002‐L1013, 2015.
 254.Hoffmann R, von Bardeleben S, ten Cate F, Borges AC, Kasprzak J, Firschke C, Lafitte S, Al‐Saadi N, Kuntz‐Hehner S, Engelhardt M, Becher H, Vanoverschelde JL. Assessment of systolic left ventricular function: A multi‐centre comparison of cineventriculography, cardiac magnetic resonance imaging, unenhanced and contrast‐enhanced echocardiography. Eur Heart J 26: 607‐616, 2005.
 255.Hofmann AD, Friedmacher F, Hunziker M, Takahashi H, Duess JW, Gosemann JH, Puri P. Upregulation of serotonin‐receptor‐2a and serotonin transporter expression in the pulmonary vasculature of nitrofen‐induced congenital diaphragmatic hernia. J Pediatr Surg 49: 871‐874; discussion 874‐875, 2014.
 256.Hofmann JJ, Iruela‐Arispe ML. Notch signaling in blood vessels: Who is talking to whom about what? Circ Res 100: 1556‐1568, 2007.
 257.Hopper RK, Moonen JR, Diebold I, Cao A, Rhodes CJ, Tojais NF, Hennigs JK, Gu M, Wang L, Rabinovitch M. In pulmonary arterial hypertension, reduced BMPR2 promotes endothelial‐to‐mesenchymal transition via HMGA1 and its target slug. Circulation 133: 1783‐1794, 2016.
 258.Houssaini A, Abid S, Mouraret N, Wan F, Rideau D, Saker M, Marcos E, Tissot CM, Dubois‐Rande JL, Amsellem V, Adnot S. Rapamycin reverses pulmonary artery smooth muscle cell proliferation in pulmonary hypertension. Am J Respir Cell Mol Biol 48: 568‐577, 2013.
 259.Hsue PY, Deeks SG, Farah HH, Palav S, Ahmed SY, Schnell A, Ellman AB, Huang L, Dollard SC, Martin JN. Role of HIV and human herpesvirus‐8 infection in pulmonary arterial hypertension. AIDS 22: 825‐833, 2008.
 260.Hu CJ, Poth JM, Zhang H, Flockton A, Laux A, Kumar S, McKeon B, Mouradian G, Li M, Riddle S, Pugliese SC, Brown RD, Wallace EM, Graham BB, Frid MG, Stenmark KR. Suppression of HIF2 signalling attenuates the initiation of hypoxia‐induced pulmonary hypertension. Eur Respir J 54: 1900378, 2019.
 261.Huddleston AJ, Knoderer CA, Morris JL, Ebenroth ES. Sildenafil for the treatment of pulmonary hypertension in pediatric patients. Pediatr Cardiol 30: 871‐882, 2009.
 262.Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 43: 13S‐24S, 2004.
 263.Humpl T, Reyes JT, Erickson S, Armano R, Holtby H, Adatia I. Sildenafil therapy for neonatal and childhood pulmonary hypertensive vascular disease. Cardiol Young 21: 187‐193, 2011.
 264.Iannone L, Zhao L, Dubois O, Duluc L, Rhodes CJ, Wharton J, Wilkins MR, Leiper J, Wojciak‐Stothard B. miR‐21/DDAH1 pathway regulates pulmonary vascular responses to hypoxia. Biochem J 462: 103‐112, 2014.
 265.Ilkiw R, Todorovich‐Hunter L, Maruyama K, Shin J, Rabinovitch M. SC‐39026, a serine elastase inhibitor, prevents muscularization of peripheral arteries, suggesting a mechanism of monocrotaline‐induced pulmonary hypertension in rats. Circ Res 64: 814‐825, 1989.
 266.Iocono JA, Cilley RE, Mauger DT, Krummel TM, Dillon PW. Postnatal pulmonary hypertension after repair of congenital diaphragmatic hernia: Predicting risk and outcome. J Pediatr Surg 34: 349‐353, 1999.
 267.Irodova NL, Lankin VZ, Konovalova GK, Kochetov AG, Chazova IE. Oxidative stress in patients with primary pulmonary hypertension. Bull Exp Biol Med 133: 580‐582, 2002.
 268.Ishikura K, Yamada N, Ito M, Ota S, Nakamura M, Isaka N, Nakano T. Beneficial acute effects of rho‐kinase inhibitor in patients with pulmonary arterial hypertension. Circ J 70: 174‐178, 2006.
 269.Ivanovska J, Shah S, Wong MJ, Kantores C, Jain A, Post M, Yeganeh B, Jankov RP. mTOR‐Notch3 signaling mediates pulmonary hypertension in hypoxia‐exposed neonatal rats independent of changes in autophagy. Pediatr Pulmonol 52: 1443‐1454, 2017.
 270.Ivy DD, Abman SH, Barst RJ, Berger RM, Bonnet D, Fleming TR, Haworth SG, Raj JU, Rosenzweig EB, Schulze Neick I, Steinhorn RH, Beghetti M. Pediatric pulmonary hypertension. J Am Coll Cardiol 62: D117‐D126, 2013.
 271.Ivy DD, Claussen L, Doran A. Transition of stable pediatric patients with pulmonary arterial hypertension from intravenous epoprostenol to intravenous treprostinil. Am J Cardiol 99: 696‐698, 2007.
 272.Ivy DD, Doran A, Claussen L, Bingaman D, Yetman A. Weaning and discontinuation of epoprostenol in children with idiopathic pulmonary arterial hypertension receiving concomitant bosentan. Am J Cardiol 93: 943‐946, 2004.
 273.Ivy DD, Doran AK, Smith KJ, Mallory GB Jr, Beghetti M, Barst RJ, Brady D, Law Y, Parker D, Claussen L, Abman SH. Short‐ and long‐term effects of inhaled iloprost therapy in children with pulmonary arterial hypertension. J Am Coll Cardiol 51: 161‐169, 2008.
 274.Ivy DD, Rosenzweig EB, Lemarie JC, Brand M, Rosenberg D, Barst RJ. Long‐term outcomes in children with pulmonary arterial hypertension treated with bosentan in real‐world clinical settings. Am J Cardiol 106: 1332‐1338, 2010.
 275.Izikki M, Guignabert C, Fadel E, Humbert M, Tu L, Zadigue P, Dartevelle P, Simonneau G, Adnot S, Maitre B, Raffestin B, Eddahibi S. Endothelial‐derived FGF2 contributes to the progression of pulmonary hypertension in humans and rodents. J Clin Invest 119: 512‐523, 2009.
 276.Janda S, Shahidi N, Gin K, Swiston J. Diagnostic accuracy of echocardiography for pulmonary hypertension: A systematic review and meta‐analysis. Heart 97: 612‐622, 2011.
 277.Jeffery TK, Morrell NW. Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension. Prog Cardiovasc Dis 45: 173‐202, 2002.
 278.Jiang L, Sun W, Zhang K, Zhou B, Kong X. Perioperative sildenafil therapy in pediatric congenital cardiac disease patients. Int Heart J 59: 1333‐1339, 2018.
 279.Jiang X, Wang YF, Zhao QH, Jiang R, Wu Y, Peng FH, Xu XQ, Wang L, He J, Jing ZC. Acute hemodynamic response of infused fasudil in patients with pulmonary arterial hypertension: A randomized, controlled, crossover study. Int J Cardiol 177: 61‐65, 2014.
 280.Johnson SR, Granton JT. Pulmonary hypertension in systemic sclerosis and systemic lupus erythematosus. Eur Respir Rev 20: 277‐286, 2011.
 281.Jone PN, Hinzman J, Wagner BD, Ivy DD, Younoszai A. Right ventricular to left ventricular diameter ratio at end‐systole in evaluating outcomes in children with pulmonary hypertension. J Am Soc Echocardiogr 27: 172‐178, 2014.
 282.Jone PN, Ivy DD. Echocardiography in pediatric pulmonary hypertension. Front Pediatr 2: 124, 2014.
 283.Jone PN, Patel SS, Cassidy C, Ivy DD. Three‐dimensional echocardiography of right ventricular function correlates with severity of pediatric pulmonary hypertension. Congenit Heart Dis 11: 562‐569, 2016.
 284.Jone PN, Schafer M, Pan Z, Ivy DD. Right ventricular‐arterial coupling ratio derived from 3‐dimensional echocardiography predicts outcomes in pediatric pulmonary hypertension. Circ Cardiovasc Imaging 12: e008176, 2019.
 285.Kaestner M, Schranz D, Warnecke G, Apitz C, Hansmann G, Miera O. Pulmonary hypertension in the intensive care unit. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 102 (Suppl 2): ii57‐ii66, 2016.
 286.Kamezaki F, Tasaki H, Yamashita K, Tsutsui M, Koide S, Nakata S, Tanimoto A, Okazaki M, Sasaguri Y, Adachi T, Otsuji Y. Gene transfer of extracellular superoxide dismutase ameliorates pulmonary hypertension in rats. Am J Respir Crit Care Med 177: 219‐226, 2008.
 287.Kamin DS, Grinspoon SK. Cardiovascular disease in HIV‐positive patients. AIDS 19: 641‐652, 2005.
 288.Kanaan U, Srivatsa B, Huckaby J, Kelleman M. Association of unit‐wide oxygen saturation target on incidence of pulmonary hypertension in very low birthweight premature infants. J Perinatol 38: 148‐153, 2018.
 289.Kang BY, Kleinhenz JM, Murphy TC, Hart CM. The PPARgamma ligand rosiglitazone attenuates hypoxia‐induced endothelin signaling in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol 301: L881‐L891, 2011.
 290.Kasahara Y, Tuder RM, Taraseviciene‐Stewart L, Le Cras TD, Abman S, Hirth PK, Waltenberger J, Voelkel NF. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 106: 1311‐1319, 2000.
 291.Katz J, Whang J, Boxt LM, Barst RJ. Estimation of right ventricular mass in normal subjects and in patients with primary pulmonary hypertension by nuclear magnetic resonance imaging. J Am Coll Cardiol 21: 1475‐1481, 1993.
 292.Keijzer R, Liu J, Deimling J, Tibboel D, Post M. Dual‐hit hypothesis explains pulmonary hypoplasia in the nitrofen model of congenital diaphragmatic hernia. Am J Pathol 156: 1299‐1306, 2000.
 293.Keith IM, Tjen ALS, Kraiczi H, Ekman R. Three‐week neonatal hypoxia reduces blood CGRP and causes persistent pulmonary hypertension in rats. Am J Physiol Heart Circ Physiol 279: H1571‐H1578, 2000.
 294.Kelly LE, Ohlsson A, Shah PS. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev 8: CD005494, 2017.
 295.Kerstjens‐Frederikse WS, Bongers EM, Roofthooft MT, Leter EM, Douwes JM, Van Dijk A, Vonk‐Noordegraaf A, Dijk‐Bos KK, Hoefsloot LH, Hoendermis ES, Gille JJ, Sikkema‐Raddatz B, Hofstra RM, Berger RM. TBX4 mutations (small patella syndrome) are associated with childhood‐onset pulmonary arterial hypertension. J Med Genet 50: 500‐506, 2013.
 296.Kheyfets VO, Sucharov CC, Truong U, Dunning J, Hunter K, Ivy D, Miyamoto S, Shandas R. Circulating miRNAs in pediatric pulmonary hypertension show promise as biomarkers of vascular function. Oxid Med Cell Longev 2017: 4957147, 2017.
 297.King ME, Braun H, Goldblatt A, Liberthson R, Weyman AE. Interventricular septal configuration as a predictor of right ventricular systolic hypertension in children: A cross‐sectional echocardiographic study. Circulation 68: 68‐75, 1983.
 298.Kinsella JP. Inhaled nitric oxide therapy in premature newborns. Curr Opin Pediatr 18: 107‐111, 2006.
 299.Kinsella JP, Cutter GR, Steinhorn RH, Nelin LD, Walsh WF, Finer NN, Abman SH. Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in premature newborns. J Pediatr 165: 1104‐1108. e1101, 2014.
 300.Kinsella JP, Cutter GR, Walsh WF, Gerstmann DR, Bose CL, Hart C, Sekar KC, Auten RL, Bhutani VK, Gerdes JS, George TN, Southgate WM, Carriedo H, Couser RJ, Mammel MC, Hall DC, Pappagallo M, Sardesai S, Strain JD, Baier M, Abman SH. Early inhaled nitric oxide therapy in premature newborns with respiratory failure. N Engl J Med 355: 354‐364, 2006.
 301.Kinsella JP, Steinhorn RH, Krishnan US, Feinstein JA, Adatia I, Austin ED, Rosenzweig EB, Everett AD, Fineman JR, Hanna BD, Hopper RK, Humpl T, Ivy DD, Keller RL, Mullen MP, Raj JU, Wessel DL, Abman SH. Recommendations for the use of inhaled nitric oxide therapy in premature newborns with severe pulmonary hypertension. J Pediatr 170: 312‐314, 2016.
 302.Kinsella JP, Steinhorn RH, Mullen MP, Hopper RK, Keller RL, Ivy DD, Austin ED, Krishnan US, Rosenzweig EB, Fineman JR, Everett AD, Hanna BD, Humpl T, Raj JU, Abman SH, Pediatric Pulmonary Hypertension N. The left ventricle in congenital diaphragmatic hernia: implications for the management of pulmonary hypertension. J Pediatr 197: 17‐22, 2018.
 303.Kinsella JP, Truog WE, Walsh WF, Goldberg RN, Bancalari E, Mayock DE, Redding GJ, deLemos RA, Sardesai S, McCurnin DC, Moreland SG, Cutter GR, Abman SH. Randomized, multicenter trial of inhaled nitric oxide and high‐frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn. J Pediatr 131: 55‐62, 1997.
 304.Kinsella JP, Walsh WF, Bose CL, Gerstmann DR, Labella JJ, Sardesai S, Walsh‐Sukys MC, McCaffrey MJ, Cornfield DN, Bhutani VK, Cutter GR, Baier M, Abman SH. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: A randomised controlled trial. Lancet 354: 1061‐1065, 1999.
 305.Kirkpatrick EC. Echocardiography in pediatric pulmonary hypertension. Paediatr Respir Rev 14: 157‐164, 2013.
 306.Klinger JR, Abman SH, Gladwin MT. Nitric oxide deficiency and endothelial dysfunction in pulmonary arterial hypertension. Am J Respir Crit Care Med 188: 639‐646, 2013.
 307.Koch S, Claesson‐Welsh L. Signal transduction by vascular endothelial growth factor receptors. Cold Spring Harb Perspect Med 2: a006502, 2012.
 308.Koestenberger M, Apitz C, Abdul‐Khaliq H, Hansmann G. Transthoracic echocardiography for the evaluation of children and adolescents with suspected or confirmed pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and D6PK. Heart 102 (Suppl 2): ii14‐ii22, 2016.
 309.Koestenberger M, Avian A, Cantinotti M, Meinel K, Hansmann G. A novel echocardiographic approach indicates disease severity in pediatric pulmonary hypertension. Pediatr Int, 2020.
 310.Koestenberger M, Friedberg MK, Nestaas E, Michel‐Behnke I, Hansmann G. Transthoracic echocardiography in the evaluation of pediatric pulmonary hypertension and ventricular dysfunction. Pulm Circ 6: 15‐29, 2016.
 311.Koestenberger M, Nagel B, Ravekes W, Urlesberger B, Raith W, Avian A, Halb V, Cvirn G, Fritsch P, Gamillscheg A. 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 100: 85‐92, 2011.
 312.Konduri GG. New approaches for persistent pulmonary hypertension of newborn. Clin Perinatol 31: 591‐611, 2004.
 313.Konduri GG, Bakhutashvili I, Eis A, Gauthier KM. Impaired voltage gated potassium channel responses in a fetal lamb model of persistent pulmonary hypertension of the newborn. Pediatr Res 66: 289‐294, 2009.
 314.Konduri GG, Bakhutashvili I, Eis A, Pritchard K Jr. Oxidant stress from uncoupled nitric oxide synthase impairs vasodilation in fetal lambs with persistent pulmonary hypertension. Am J Physiol Heart Circ Physiol 292: H1812‐H1820, 2007.
 315.Konduri GG, Kim UO. Advances in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatr Clin North Am 56: 579‐600, Table of Contents, 2009.
 316.Konduri GG, Solimano A, Sokol GM, Singer J, Ehrenkranz RA, Singhal N, Wright LL, Van Meurs K, Stork E, Kirpalani H, Peliowski A, Neonatal Inhaled Nitric Oxide Study G. A randomized trial of early versus standard inhaled nitric oxide therapy in term and near‐term newborn infants with hypoxic respiratory failure. Pediatrics 113: 559‐564, 2004.
 317.Konduri GG, Vohr B, Robertson C, Sokol GM, Solimano A, Singer J, Ehrenkranz RA, Singhal N, Wright LL, Van Meurs K, Stork E, Kirpalani H, Peliowski A, Johnson Y, Neonatal Inhaled Nitric Oxide Study G. Early inhaled nitric oxide therapy for term and near‐term newborn infants with hypoxic respiratory failure: Neurodevelopmental follow‐up. J Pediatr 150: 235‐240 e231, 2007.
 318.Kopan R, Ilagan MX. The canonical Notch signaling pathway: Unfolding the activation mechanism. Cell 137: 216‐233, 2009.
 319.Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: A systematic review. Eur Respir J 34: 888‐894, 2009.
 320.Krishnan U, Feinstein JA, Adatia I, Austin ED, Mullen MP, Hopper RK, Hanna B, Romer L, Keller RL, Fineman J, Steinhorn R, Kinsella JP, Ivy DD, Rosenzweig EB, Raj U, Humpl T, Abman SH, Pediatric Pulmonary Hypertension N. Evaluation and management of pulmonary hypertension in children with bronchopulmonary dysplasia. J Pediatr 188: 24‐34. e21, 2017.
 321.Kunichika N, Landsberg JW, Yu Y, Kunichika H, Thistlethwaite PA, Rubin LJ, Yuan JX. Bosentan inhibits transient receptor potential channel expression in pulmonary vascular myocytes. Am J Respir Crit Care Med 170: 1101‐1107, 2004.
 322.Kurath‐Koller S, Avian A, Cantinotti M, Burmas A, Grangl G, Schweintzger S, Gamillscheg A, Koestenberger M. Normal pediatric values of the subcostal tricuspid annular plane systolic excursion (S‐TAPSE) and its value in pediatric pulmonary hypertension. Can J Cardiol 35: 899‐906, 2019.
 323.Kuzuya K, Tsuji S, Matsushita M, Ohshima S, Saeki Y. Systemic sclerosis and systemic lupus erythematosus overlap syndrome with pulmonary arterial hypertension successfully treated with immunosuppressive therapy and riociguat. Cureus 11: e4327, 2019.
 324.La Gerche A, Jurcut R, Voigt JU. Right ventricular function by strain echocardiography. Curr Opin Cardiol 25: 430‐436, 2010.
 325.Lagatta JM, Hysinger EB, Zaniletti I, Wymore EM, Vyas‐Read S, Yallapragada S, Nelin LD, Truog WE, Padula MA, Porta NFM, Savani RC, Potoka KP, Kawut SM, DiGeronimo R, Natarajan G, Zhang H, Grover TR, Engle WA, Murthy K, Children's Hospital Neonatal Consortium Severe BPDFG. The impact of pulmonary hypertension in preterm infants with severe bronchopulmonary dysplasia through 1 year. J Pediatr 203: 218‐224. e213, 2018.
 326.Lakshminrusimha S, Steinhorn RH. Pulmonary vascular biology during neonatal transition. Clin Perinatol 26: 601‐619, 1999.
 327.Laliberte C, Hanna Y, Ben Fadel N, Lemyre B, Bijelic V, Barrowman N, Hoey L, Thebaud B, Katz SL. Target oxygen saturation and development of pulmonary hypertension and increased pulmonary vascular resistance in preterm infants. Pediatr Pulmonol 54: 73‐81, 2019.
 328.Lammers AE, Adatia I, Cerro MJ, Diaz G, Freudenthal AH, Freudenthal F, Harikrishnan S, Ivy D, Lopes AA, Raj JU, Sandoval J, Stenmark K, Haworth SG. Functional classification of pulmonary hypertension in children: Report from the PVRI pediatric taskforce, Panama 2011. Pulm Circ 1: 280‐285, 2011.
 329.Lammers AE, Apitz C, Zartner P, Hager A, Dubowy KO, Hansmann G. Diagnostics, monitoring and outpatient care in children with suspected pulmonary hypertension/paediatric pulmonary hypertensive vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 102 (Suppl 2): ii1‐ii13, 2016.
 330.Lammers AE, Hislop AA, Flynn Y, Haworth SG. The 6‐minute walk test: Normal values for children of 4‐11 years of age. Arch Dis Child 93: 464‐468, 2008.
 331.Landsberg JW, Yuan JX. Calcium and TRP channels in pulmonary vascular smooth muscle cell proliferation. News Physiol Sci 19: 44‐50, 2004.
 332.Lassus P, Turanlahti M, Heikkila P, Andersson LC, Nupponen I, Sarnesto A, Andersson S. Pulmonary vascular endothelial growth factor and Flt‐1 in fetuses, in acute and chronic lung disease, and in persistent pulmonary hypertension of the newborn. Am J Respir Crit Care Med 164: 1981‐1987, 2001.
 333.Latus H, Kuehne T, Beerbaum P, Apitz C, Hansmann G, Muthurangu V, Moledina S. Cardiac MR and CT imaging in children with suspected or confirmed pulmonary hypertension/pulmonary hypertensive vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 102 (Suppl 2): ii30‐ii35, 2016.
 334.Lau KC, Frank DB, Hanna BD, Patel AR. Utility of electrocardiogram in the assessment and monitoring of pulmonary hypertension (idiopathic or secondary to pulmonary developmental abnormalities) in patients ≤18 years of age. Am J Cardiol 114: 294‐299, 2014.
 335.Laufs U, Liao JK. Post‐transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 273: 24266‐24271, 1998.
 336.Laurikainen E, Aitasalo K, Erkinjuntti M, Wanne O. Sleep apnea syndrome in children–secondary to adenotonsillar hypertrophy? Acta Otolaryngol Suppl 492: 38‐41, 1992.
 337.Law MA, Grifka RG, Mullins CE, Nihill MR. Atrial septostomy improves survival in select patients with pulmonary hypertension. Am Heart J 153: 779‐784, 2007.
 338.Lawrence KM, Monos S, Adams S, Herkert L, Peranteau WH, Munson DA, Hopper RK, Avitabile CM, Rintoul NE, Hedrick HL. Inhaled nitric oxide is associated with improved oxygenation in a subpopulation of infants with congenital diaphragmatic hernia and pulmonary hypertension. J Pediatr 219: 167‐172, 2020.
 339.Lawrie A, Spiekerkoetter E, Martinez EC, Ambartsumian N, Sheward WJ, MacLean MR, Harmar AJ, Schmidt AM, Lukanidin E, Rabinovitch M. Interdependent serotonin transporter and receptor pathways regulate S100A4/Mts1, a gene associated with pulmonary vascular disease. Circ Res 97: 227‐235, 2005.
 340.Le Cras TD, Kim DH, Gebb S, Markham NE, Shannon JM, Tuder RM, Abman SH. Abnormal lung growth and the development of pulmonary hypertension in the Fawn‐Hooded rat. Am J Physiol 277: L709‐L718, 1999.
 341.Le Cras TD, Markham NE, Tuder RM, Voelkel NF, Abman SH. Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure. Am J Physiol Lung Cell Mol Physiol 283: L555‐L562, 2002.
 342.Lee KJ, Berkelhamer SK, Kim GA, Taylor JM, O'Shea KM, Steinhorn RH, Farrow KN. Disrupted pulmonary artery cyclic guanosine monophosphate signaling in mice with hyperoxia‐induced pulmonary hypertension. Am J Respir Cell Mol Biol 50: 369‐378, 2014.
 343.Lee MR, Li L, Kitazawa T. Cyclic GMP causes Ca2+ desensitization in vascular smooth muscle by activating the myosin light chain phosphatase. J Biol Chem 272: 5063‐5068, 1997.
 344.Lee SL, Wang WW, Finlay GA, Fanburg BL. Serotonin stimulates mitogen‐activated protein kinase activity through the formation of superoxide anion. Am J Physiol 277: L282‐L291, 1999.
 345.Lepetit H, Eddahibi S, Fadel E, Frisdal E, Munaut C, Noel A, Humbert M, Adnot S, D'Ortho MP, Lafuma C. Smooth muscle cell matrix metalloproteinases in idiopathic pulmonary arterial hypertension. Eur Respir J 25: 834‐842, 2005.
 346.Levy M, Bonnet D, Mauge L, Celermajer DS, Gaussem P, Smadja DM. Circulating endothelial cells in refractory pulmonary hypertension in children: Markers of treatment efficacy and clinical worsening. PLoS One 8: e65114, 2013.
 347.Levy M, Eyries M, Szezepanski I, Ladouceur M, Nadaud S, Bonnet D, Soubrier F. Genetic analyses in a cohort of children with pulmonary hypertension. Eur Respir J 48: 1118‐1126, 2016.
 348.Li H, Chen SJ, Chen YF, Meng QC, Durand J, Oparil S, Elton TS. Enhanced endothelin‐1 and endothelin receptor gene expression in chronic hypoxia. J Appl Physiol (1985) 77: 1451‐1459, 1994.
 349.Li L, Jick S, Breitenstein S, Hernandez G, Michel A, Vizcaya D. Pulmonary arterial hypertension in the USA: An epidemiological study in a large insured pediatric population. Pulm Circ 7: 126‐136, 2017.
 350.Li M, Liu Y, Jin F, Sun X, Li Z, Liu Y, Fang P, Shi H, Jiang X. Endothelin‐1 induces hypoxia inducible factor 1alpha expression in pulmonary artery smooth muscle cells. FEBS Lett 586: 3888‐3893, 2012.
 351.Li R, Zhang J. Diagnostic value of chest CT combined with X‐ray for premature infants with bronchopulmonary dysplasia. Medicine (Baltimore) 97: e9723, 2018.
 352.Li X, Zhang X, Leathers R, Makino A, Huang C, Parsa P, Macias J, Yuan JX, Jamieson SW, Thistlethwaite PA. Notch3 signaling promotes the development of pulmonary arterial hypertension. Nat Med 15: 1289‐1297, 2009.
 353.Li Y, Xie M, Wang X, Lu Q, Fu M. Right ventricular regional and global systolic function is diminished in patients with pulmonary arterial hypertension: A 2‐dimensional ultrasound speckle tracking echocardiography study. Int J Cardiovasc Imaging 29: 545‐551, 2013.
 354.Limsuwan A, Khosithseth A, Wanichkul S, Khowsathit P. Aerosolized iloprost for pulmonary vasoreactivity testing in children with long‐standing pulmonary hypertension related to congenital heart disease. Catheter Cardiovasc Interv 73: 98‐104, 2009.
 355.Limsuwan A, Khowsathit P. Assessment of pulmonary vasoreactivity in children with pulmonary hypertension. Curr Opin Pediatr 21: 594‐599, 2009.
 356.Limsuwan A, Wanitkul S, Khosithset A, Attanavanich S, Samankatiwat P. Aerosolized iloprost for postoperative pulmonary hypertensive crisis in children with congenital heart disease. Int J Cardiol 129: 333‐338, 2008.
 357.Lin MJ, Leung GP, Zhang WM, Yang XR, Yip KP, Tse CM, Sham JS. Chronic hypoxia‐induced upregulation of store‐operated and receptor‐operated Ca2+ channels in pulmonary arterial smooth muscle cells: A novel mechanism of hypoxic pulmonary hypertension. Circ Res 95: 496‐505, 2004.
 358.Liu CQ, Ma L, Tang LM, He XJ, Wei SF, Wang SX, Zhang GY. A randomized controlled study on the efficacy of inhaled nitric oxide in treatment of neonates with meconium aspiration syndrome. Zhonghua Er Ke Za Zhi 46: 224‐228, 2008.
 359.Loh E, Stamler JS, Hare JM, Loscalzo J, Colucci WS. Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction. Circulation 90: 2780‐2785, 1994.
 360.Lohani O, Colvin KL, Yeager ME. Biomarkers for pediatric pulmonary arterial hypertension: Challenges and recommendations. Paediatr Respir Rev 16: 225‐231, 2015.
 361.Long L, MacLean MR, Jeffery TK, Morecroft I, Yang X, Rudarakanchana N, Southwood M, James V, Trembath RC, Morrell NW. Serotonin increases susceptibility to pulmonary hypertension in BMPR2‐deficient mice. Circ Res 98: 818‐827, 2006.
 362.Lopes A, and Barst R. A proposed algorithm for management of patients with congenital cardiac defects associated with pulmonary hypertension. https://pvrinstitute.org
 363.Lu X, Nadvoretskiy V, Bu L, Stolpen A, Ayres N, Pignatelli RH, Kovalchin JP, Grenier M, Klas B, Ge S. Accuracy and reproducibility of real‐time three‐dimensional echocardiography for assessment of right ventricular volumes and ejection fraction in children. J Am Soc Echocardiogr 21: 84‐89, 2008.
 364.Luscher TF, Barton M. Endothelins and endothelin receptor antagonists: Therapeutic considerations for a novel class of cardiovascular drugs. Circulation 102: 2434‐2440, 2000.
 365.Lyle AN, Griendling KK. Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology (Bethesda) 21: 269‐280, 2006.
 366.Maarman G, Lecour S, Butrous G, Thienemann F, Sliwa K. A comprehensive review: The evolution of animal models in pulmonary hypertension research; are we there yet? Pulm Circ 3: 739‐756, 2013.
 367.Machado RD, Eickelberg O, Elliott CG, Geraci MW, Hanaoka M, Loyd JE, Newman JH, Phillips JA 3rd, Soubrier F, Trembath RC, Chung WK. Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol 54: S32‐S42, 2009.
 368.Madani MM, Wittine LM, Auger WR, Fedullo PF, Kerr KM, Kim NH, Test VJ, Kriett JM, Jamieson SW. Chronic thromboembolic pulmonary hypertension in pediatric patients. J Thorac Cardiovasc Surg 141: 624‐630, 2011.
 369.Mahajan CN, Afolayan AJ, Eis A, Teng RJ, Konduri GG. Altered prostanoid metabolism contributes to impaired angiogenesis in persistent pulmonary hypertension in a fetal lamb model. Pediatr Res 77: 455‐462, 2015.
 370.Mahgoub L, Kaddoura T, Kameny AR, Lopez Ortego P, Vanderlaan RD, Kakadekar A, Dicke F, Rebeyka I, Calderone CA, Redington A, Del Cerro MJ, Fineman J, Adatia I. Pulmonary vein stenosis of ex‐premature infants with pulmonary hypertension and bronchopulmonary dysplasia, epidemiology, and survival from a multicenter cohort. Pediatr Pulmonol 52: 1063‐1070, 2017.
 371.Maiya S, Hislop AA, Flynn Y, Haworth SG. Response to bosentan in children with pulmonary hypertension. Heart 92: 664‐670, 2006.
 372.Majesky MW. Adventitia and perivascular cells. Arterioscler Thromb Vasc Biol 35: e31‐e35, 2015.
 373.Makker K, Afolayan AJ, Teng RJ, Konduri GG. Altered hypoxia‐inducible factor‐1alpha (HIF‐1alpha) signaling contributes to impaired angiogenesis in fetal lambs with persistent pulmonary hypertension of the newborn (PPHN). Physiol Rep 7: e13986, 2019.
 374.Malowitz JR, Forsha DE, Smith PB, Cotten CM, Barker PC, Tatum GH. Right ventricular echocardiographic indices predict poor outcomes in infants with persistent pulmonary hypertension of the newborn. Eur Heart J Cardiovasc Imaging 16: 1224‐1231, 2015.
 375.Maron BA, Brittain EL, Choudhary G, Gladwin MT. Redefining pulmonary hypertension. Lancet Respir Med 6: 168‐170, 2018.
 376.Marron MJ, Crisafi MA, Driscoll JM Jr, Wung JT, Driscoll YT, Fay TH, James LS. Hearing and neurodevelopmental outcome in survivors of persistent pulmonary hypertension of the newborn. Pediatrics 90: 392‐396, 1992.
 377.Marsboom G, Chen Z, Yuan Y, Zhang Y, Tiruppathi C, Loyd JE, Austin ED, Machado RF, Minshall RD, Rehman J, Malik AB. Aberrant caveolin‐1‐mediated Smad signaling and proliferation identified by analysis of adenine 474 deletion mutation (c.474delA) in patient fibroblasts: A new perspective on the mechanism of pulmonary hypertension. Mol Biol Cell 28: 1177‐1185, 2017.
 378.Masarwa R, Bar‐Oz B, Gorelik E, Reif S, Perlman A, Matok I. Prenatal exposure to selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors and risk for persistent pulmonary hypertension of the newborn: A systematic review, meta‐analysis, and network meta‐analysis. Am J Obstet Gynecol 220: 57 e1‐57 e13, 2019.
 379.Matsuda Y, Hoshikawa Y, Ameshima S, Suzuki S, Okada Y, Tabata T, Sugawara T, Matsumura Y, Kondo T. Effects of peroxisome proliferator‐activated receptor gamma ligands on monocrotaline‐induced pulmonary hypertension in rats. Nihon Kokyuki Gakkai Zasshi 43: 283‐288, 2005.
 380.Maxey DM, Ivy DD, Ogawa MT, Feinstein JA. Food and Drug Administration (FDA) postmarket reported side effects and adverse events associated with pulmonary hypertension therapy in pediatric patients. Pediatr Cardiol 34: 1628‐1636, 2013.
 381.McCrary AW, Barker PCA, Torok RD, Spears TG, Li JS, Hornik CP, Laughon MM. Agreement of an echocardiogram‐based diagnosis of pulmonary hypertension in infants at risk for bronchopulmonary dysplasia among masked reviewers. J Perinatol 39: 248‐255, 2019.
 382.McMurtry IF, Bauer NR, Fagan KA, Nagaoka T, Gebb SA, Oka M. Hypoxia and Rho/Rho‐kinase signaling. Lung development versus hypoxic pulmonary hypertension. Adv Exp Med Biol 543: 127‐137, 2003.
 383.McMurtry MS, Bonnet S, Wu X, Dyck JR, Haromy A, Hashimoto K, Michelakis ED. Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res 95: 830‐840, 2004.
 384.McNamara PJ, Murthy P, Kantores C, Teixeira L, Engelberts D, van Vliet T, Kavanagh BP, Jankov RP. Acute vasodilator effects of Rho‐kinase inhibitors in neonatal rats with pulmonary hypertension unresponsive to nitric oxide. Am J Physiol Lung Cell Mol Physiol 294: L205‐L213, 2008.
 385.Menendez Suso JJ, Del Cerro Marin MJ, Dorao Martinez‐Romillo P, Labrandero deLera C, Fernandez Garcia‐Moya L, Rodriguezgonzalez JI. Nonketotic hyperglycinemia presenting as pulmonary hypertensive vascular disease and fatal pulmonary edema in response to pulmonary vasodilator therapy. J Pediatr 161: 557‐559, 2012.
 386.Mercier JC, Hummler H, Durrmeyer X, Sanchez‐Luna M, Carnielli V, Field D, Greenough A, Van Overmeire B, Jonsson B, Hallman M, Baldassarre J, Group ES. Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): A randomised controlled trial. Lancet 376: 346‐354, 2010.
 387.Mestan KK, Gotteiner N, Porta N, Grobman W, Su EJ, Ernst LM. Cord blood biomarkers of placental maternal vascular underperfusion predict bronchopulmonary dysplasia‐associated pulmonary hypertension. J Pediatr 185: 33‐41, 2017.
 388.Meyrick B, Gamble W, Reid L. Development of crotalaria pulmonary hypertension: Hemodynamic and structural study. Am J Physiol 239: H692‐H702, 1980.
 389.Michelakis ED, McMurtry MS, Wu XC, Dyck JR, Moudgil R, Hopkins TA, Lopaschuk GD, Puttagunta L, Waite R, Archer SL. Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: Role of increased expression and activity of voltage‐gated potassium channels. Circulation 105: 244‐250, 2002.
 390.Micheletti A, Hislop AA, Lammers A, Bonhoeffer P, Derrick G, Rees P, Haworth SG. Role of atrial septostomy in the treatment of children with pulmonary arterial hypertension. Heart 92: 969‐972, 2006.
 391.Michiels C, Arnould T, Remacle J. Endothelial cell responses to hypoxia: Initiation of a cascade of cellular interactions. Biochim Biophys Acta 1497: 1‐10, 2000.
 392.Miele L, Golde T, Osborne B. Notch signaling in cancer. Curr Mol Med 6: 905‐918, 2006.
 393.Minai OA, Gudavalli R, Mummadi S, Liu X, McCarthy K, Dweik RA. Heart rate recovery predicts clinical worsening in patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 185: 400‐408, 2012.
 394.Miniati M, Monti S, Bottai M, Scoscia E, Bauleo C, Tonelli L, Dainelli A, Giuntini C. Survival and restoration of pulmonary perfusion in a long‐term follow‐up of patients after acute pulmonary embolism. Medicine (Baltimore) 85: 253‐262, 2006.
 395.Mitchell JA, Warner TD. Cyclo‐oxygenase‐2: Pharmacology, physiology, biochemistry and relevance to NSAID therapy. Br J Pharmacol 128: 1121‐1132, 1999.
 396.Mitchell JA, Warner TD. COX isoforms in the cardiovascular system: Understanding the activities of non‐steroidal anti‐inflammatory drugs. Nat Rev Drug Discov 5: 75‐86, 2006.
 397.Mitchell MB, Campbell DN, Ivy D, Boucek MM, Sondheimer HM, Pietra B, Das BB, Coll JR. Evidence of pulmonary vascular disease after heart transplantation for Fontan circulation failure. J Thorac Cardiovasc Surg 128: 693‐702, 2004.
 398.Mitchell WB. Thromboinflammation in COVID‐19 acute lung injury. Paediatr Respir Rev 35: 20‐24, 2020.
 399.Mohamed WA, Ismail M. A randomized, double‐blind, placebo‐controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn. J Perinatol 32: 608‐613, 2012.
 400.Mohseni‐Bod H, Bohn D. Pulmonary hypertension in congenital diaphragmatic hernia. Semin Pediatr Surg 16: 126‐133, 2007.
 401.Moledina S, Hislop AA, Foster H, Schulze‐Neick I, Haworth SG. Childhood idiopathic pulmonary arterial hypertension: A national cohort study. Heart 96: 1401‐1406, 2010.
 402.Moledina S, Pandya B, Bartsota M, Mortensen KH, McMillan M, Quyam S, Taylor AM, Haworth SG, Schulze‐Neick I, Muthurangu V. Prognostic significance of cardiac magnetic resonance imaging in children with pulmonary hypertension. Circ Cardiovasc Imaging 6: 407‐414, 2013.
 403.Mondy KE, Gottdiener J, Overton ET, Henry K, Bush T, Conley L, Hammer J, Carpenter CC, Kojic E, Patel P, Brooks JT, Investigators SUNS. High prevalence of echocardiographic abnormalities among HIV‐infected persons in the era of highly active antiretroviral therapy. Clin Infect Dis 52: 378‐386, 2011.
 404.Montalva L, Antounians L, Zani A. Pulmonary hypertension secondary to congenital diaphragmatic hernia: Factors and pathways involved in pulmonary vascular remodeling. Pediatr Res 85: 754‐768, 2019.
 405.Montani D, Girerd B, Jais X, Levy M, Amar D, Savale L, Dorfmuller P, Seferian A, Lau EM, Eyries M, Le Pavec J, Parent F, Bonnet D, Soubrier F, Fadel E, Sitbon O, Simonneau G, Humbert M. Clinical phenotypes and outcomes of heritable and sporadic pulmonary veno‐occlusive disease: A population‐based study. Lancet Respir Med 5: 125‐134, 2017.
 406.Montedonico S, Nakazawa N, Puri P. Retinoic acid rescues lung hypoplasia in nitrofen‐induced hypoplastic foetal rat lung explants. Pediatr Surg Int 22: 2‐8, 2006.
 407.Morchi GS, Ivy DD, Duster MC, Claussen L, Chan KC, Kay J. Sildenafil increases systemic saturation and reduces pulmonary artery pressure in patients with failing Fontan physiology. Congenit Heart Dis 4: 107‐111, 2009.
 408.Moreland RB, Goldstein I, Traish A. Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells. Life Sci 62: PL 309‐PL 318, 1998.
 409.Moreno‐Galdo A, Torrent‐Vernetta A, de Mir Messa I, Rovira Amigo S, Gran Pina F, Gartner S, Albert Brotons B. Use of inhaled iloprost in children with pulmonary hypertension. Pediatr Pulmonol 50: 370‐379, 2015.
 410.Moro MA, Russel RJ, Cellek S, Lizasoain I, Su Y, Darley‐Usmar VM, Radomski MW, Moncada S. cGMP mediates the vascular and platelet actions of nitric oxide: Confirmation using an inhibitor of the soluble guanylyl cyclase. Proc Natl Acad Sci USA 93: 1480‐1485, 1996.
 411.Morrell NW, Aldred MA, Chung WK, Elliott CG, Nichols WC, Soubrier F, Trembath RC, Loyd JE. Genetics and genomics of pulmonary arterial hypertension. Eur Respir J 53, 2019.
 412.Morris K, Beghetti M, Petros A, Adatia I, Bohn D. Comparison of hyperventilation and inhaled nitric oxide for pulmonary hypertension after repair of congenital heart disease. Crit Care Med 28: 2974‐2978, 2000.
 413.Morty RE, Nejman B, Kwapiszewska G, Hecker M, Zakrzewicz A, Kouri FM, Peters DM, Dumitrascu R, Seeger W, Knaus P, Schermuly RT, Eickelberg O. Dysregulated bone morphogenetic protein signaling in monocrotaline‐induced pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol 27: 1072‐1078, 2007.
 414.Moser KM, Bloor CM. Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. Chest 103: 685‐692, 1993.
 415.Moser KM, Page GT, Ashburn WL, Fedullo PF. Perfusion lung scans provide a guide to which patients with apparent primary pulmonary hypertension merit angiography. West J Med 148: 167‐170, 1988.
 416.Mourani PM, Abman SH. Pulmonary vascular disease in bronchopulmonary dysplasia: Pulmonary hypertension and beyond. Curr Opin Pediatr 25: 329‐337, 2013.
 417.Mourani PM, Ivy DD, Gao D, Abman SH. Pulmonary vascular effects of inhaled nitric oxide and oxygen tension in bronchopulmonary dysplasia. Am J Respir Crit Care Med 170: 1006‐1013, 2004.
 418.Mourani PM, Sontag MK, Younoszai A, Ivy DD, Abman SH. Clinical utility of echocardiography for the diagnosis and management of pulmonary vascular disease in young children with chronic lung disease. Pediatrics 121: 317‐325, 2008.
 419.Mourani PM, Sontag MK, Younoszai A, Miller JI, Kinsella JP, Baker CD, Poindexter BB, Ingram DA, Abman SH. Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia. Am J Respir Crit Care Med 191: 87‐95, 2015.
 420.Mukherjee A, Dombi T, Wittke B, Lalonde R. Population pharmacokinetics of sildenafil in term neonates: Evidence of rapid maturation of metabolic clearance in the early postnatal period. Clin Pharmacol Ther 85: 56‐63, 2009.
 421.Mulligan C, Beghetti M. Inhaled iloprost for the control of acute pulmonary hypertension in children: A systematic review. Pediatr Crit Care Med 13: 472‐480, 2012.
 422.Munzel T, Feil R, Mulsch A, Lohmann SM, Hofmann F, Walter U. Physiology and pathophysiology of vascular signaling controlled by guanosine 3',5'‐cyclic monophosphate‐dependent protein kinase [ corrected]. Circulation 108: 2172‐2183, 2003.
 423.Muraskas JK, Juretschke LJ, Weiss MG, Bhola M, Besinger RE. Neonatal‐perinatal risk factors for the development of persistent pulmonary hypertension of the newborn in preterm newborns. Am J Perinatol 18: 87‐91, 2001.
 424.Muzaffar S, Shukla N, Bond M, Sala‐Newby GB, Newby AC, Angelini GD, Jeremy JY. Superoxide from NADPH oxidase upregulates type 5 phosphodiesterase in human vascular smooth muscle cells: Inhibition with iloprost and NONOate. Br J Pharmacol 155: 847‐856, 2008.
 425.Naeem B, Ayub A, Aly AM, Malloy MH, Okorodudu AO, Jain SK. Urinary NT‐proBNP as a potential noninvasive biomarker for screening of pulmonary hypertension in preterm infants: A pilot study. J Perinatol 40: 628‐632, 2020.
 426.Naeije R, Chin K. Differentiating precapillary from postcapillary pulmonary hypertension. Circulation 140: 712‐714, 2019.
 427.Naeije R, Gerges M, Vachiery JL, Caravita S, Gerges C, Lang IM. Hemodynamic phenotyping of pulmonary hypertension in left heart failure. Circ Heart Fail 10: e004082, 2017.
 428.Naeije R, Vachiery JL, Yerly P, Vanderpool R. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur Respir J 41: 217‐223, 2013.
 429.Nagaoka T, Morio Y, Casanova N, Bauer N, Gebb S, McMurtry I, Oka M. Rho/Rho kinase signaling mediates increased basal pulmonary vascular tone in chronically hypoxic rats. Am J Physiol Lung Cell Mol Physiol 287: L665‐L672, 2004.
 430.Nair J, Lakshminrusimha S. Update on PPHN: Mechanisms and treatment. Semin Perinatol 38: 78‐91, 2014.
 431.Nakanishi H, Morikawa S, Kitahara S, Yoshii A, Uchiyama A, Kusuda S, Ezaki T. Morphological characterization of pulmonary microvascular disease in bronchopulmonary dysplasia caused by hyperoxia in newborn mice. Med Mol Morphol 51: 166‐175, 2018.
 432.Namachivayam P, Theilen U, Butt WW, Cooper SM, Penny DJ, Shekerdemian LS. Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. Am J Respir Crit Care Med 174: 1042‐1047, 2006.
 433.Negash S, Narasimhan SR, Zhou W, Liu J, Wei FL, Tian J, Raj JU. Role of cGMP‐dependent protein kinase in regulation of pulmonary vascular smooth muscle cell adhesion and migration: Effect of hypoxia. Am J Physiol Heart Circ Physiol 297: H304‐H312, 2009.
 434.Nemoto S, Sasaki T, Ozawa H, Katsumata T, Kishi K, Okumura K, Mori Y, Umegaki O. Oral sildenafil for persistent pulmonary hypertension early after congenital cardiac surgery in children. Eur J Cardiothorac Surg 38: 71‐77, 2010.
 435.Neonatal Inhaled Nitric Oxide Study G. Inhaled nitric oxide in full‐term and nearly full‐term infants with hypoxic respiratory failure. N Engl J Med 336: 597‐604, 1997.
 436.Network SSGotEKSNNR, Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Schibler K, Newman NS, Ambalavanan N, Frantz ID 3rd, Piazza AJ, Sanchez PJ, Morris BH, Laroia N, Phelps DL, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Ehrenkranz RA, Watterberg KL, Higgins RD. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med 362: 1959‐1969, 2010.
 437.Ni JR, Yan PJ, Liu SD, Hu Y, Yang KH, Song B, Lei JQ. Diagnostic accuracy of transthoracic echocardiography for pulmonary hypertension: A systematic review and meta‐analysis. BMJ Open 9: e033084, 2019.
 438.Nickel N, Golpon H, Greer M, Knudsen L, Olsson K, Westerkamp V, Welte T, Hoeper MM. The prognostic impact of follow‐up assessments in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 39: 589‐596, 2012.
 439.Nicolarsen J, Ivy D. Progress in the diagnosis and management of pulmonary hypertension in children. Curr Opin Pediatr 26: 527‐535, 2014.
 440.Nir A, Lindinger A, Rauh M, Bar‐Oz B, Laer S, Schwachtgen L, Koch A, Falkenberg J, Mir TS. NT‐pro‐B‐type natriuretic peptide in infants and children: Reference values based on combined data from four studies. Pediatr Cardiol 30: 3‐8, 2009.
 441.Nisbet RE, Bland JM, Kleinhenz DJ, Mitchell PO, Walp ER, Sutliff RL, Hart CM. Rosiglitazone attenuates chronic hypoxia‐induced pulmonary hypertension in a mouse model. Am J Respir Cell Mol Biol 42: 482‐490, 2010.
 442.Nishida M, Eshiro K, Okada Y, Takaoka M, Matsumura Y. Roles of endothelin ETA and ETB receptors in the pathogenesis of monocrotaline‐induced pulmonary hypertension. J Cardiovasc Pharmacol 44: 187‐191, 2004.
 443.Nozik‐Grayck E, Suliman HB, Majka S, Albietz J, Van Rheen Z, Roush K, Stenmark KR. Lung EC‐SOD overexpression attenuates hypoxic induction of Egr‐1 and chronic hypoxic pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol 295: L422‐L430, 2008.
 444.O'Byrne ML, Glatz AC, Hanna BD, Shinohara RT, Gillespie MJ, Dori Y, Rome JJ, Kawut SM. Predictors of catastrophic adverse outcomes in children with pulmonary hypertension undergoing cardiac catheterization: A multi‐institutional analysis from the pediatric health information systems database. J Am Coll Cardiol 66: 1261‐1269, 2015.
 445.O'Byrne ML, Kennedy KF, Kanter JP, Berger JT, Glatz AC. Risk factors for major early adverse events related to cardiac catheterization in children and young adults with pulmonary hypertension: An analysis of data from the IMPACT (improving adult and congenital treatment) registry. J Am Heart Assoc 7, 2018. DOI: 10.1161/JAHA.117.008142.
 446.Ohi R, Suzuki H, Kato T, Kasai M. Development of the lung in fetal rabbits with experimental diaphragmatic hernia. J Pediatr Surg 11: 955‐959, 1976.
 447.Oka M, Homma N, Taraseviciene‐Stewart L, Morris KG, Kraskauskas D, Burns N, Voelkel NF, McMurtry IF. Rho kinase‐mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats. Circ Res 100: 923‐929, 2007.
 448.Okumura K, Humpl T, Dragulescu A, Mertens L, Friedberg MK. Longitudinal assessment of right ventricular myocardial strain in relation to transplant‐free survival in children with idiopathic pulmonary hypertension. J Am Soc Echocardiogr 27: 1344‐1351, 2014.
 449.Olguin HJ, Martinez HO, Perez CF, Mendiola BR, Espinosa LR, Pacheco JLC, Perez JF, Magana IM. Pharmacokinetics of sildenafil in children with pulmonary arterial hypertension. World J Pediatr 13: 588‐592, 2017.
 450.Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, Nikkho S, Speich R, Hoeper MM, Behr J, Winkler J, Sitbon O, Popov W, Ghofrani HA, Manes A, Kiely DG, Ewert R, Meyer A, Corris PA, Delcroix M, Gomez‐Sanchez M, Siedentop H, Seeger W, Aerosolized Iloprost Randomized Study G. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 347: 322‐329, 2002.
 451.Olson LJ, Knych ET Jr, Herzig TC, Drewett JG. Selective guanylyl cyclase inhibitor reverses nitric oxide‐induced vasorelaxation. Hypertension 29: 254‐261, 1997.
 452.Ono M, Sawa Y, Fukushima N, Suhara H, Nakamura T, Yokoyama C, Tanabe T, Matsuda H. Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats. Eur J Cardiothorac Surg 26: 1092‐1097, 2004.
 453.Ono M, Sawa Y, Mizuno S, Fukushima N, Ichikawa H, Bessho K, Nakamura T, Matsuda H. Hepatocyte growth factor suppresses vascular medial hyperplasia and matrix accumulation in advanced pulmonary hypertension of rats. Circulation 110: 2896‐2902, 2004.
 454.Opotowsky AR. Clinical evaluation and management of pulmonary hypertension in the adult with congenital heart disease. Circulation 131: 200‐210, 2015.
 455.Ovaert C, Thijs D, Dewolf D, Ottenkamp J, Dessy H, Moons P, Gewillig M, Mertens L. The effect of bosentan in patients with a failing Fontan circulation. Cardiol Young 19: 331‐339, 2009.
 456.Paciocco G, Martinez FJ, Bossone E, Pielsticker E, Gillespie B, Rubenfire M. Oxygen desaturation on the six‐minute walk test and mortality in untreated primary pulmonary hypertension. Eur Respir J 17: 647‐652, 2001.
 457.Packer M. Pathophysiological mechanisms underlying the adverse effects of calcium channel‐blocking drugs in patients with chronic heart failure. Circulation 80: IV59‐IV67, 1989.
 458.Paddenberg R, Stieger P, von Lilien AL, Faulhammer P, Goldenberg A, Tillmanns HH, Kummer W, Braun‐Dullaeus RC. Rapamycin attenuates hypoxia‐induced pulmonary vascular remodeling and right ventricular hypertrophy in mice. Respir Res 8: 15, 2007.
 459.Paffett ML, Naik JS, Resta TC, Walker BR. Reduced store‐operated Ca2+ entry in pulmonary endothelial cells from chronically hypoxic rats. Am J Physiol Lung Cell Mol Physiol 293: L1135‐L1142, 2007.
 460.Palma G, Giordano R, Russolillo V, Cioffi S, Palumbo S, Mucerino M, Poli V, Vosa C. Sildenafil therapy for pulmonary hypertension before and after pediatric congenital heart surgery. Tex Heart Inst J 38: 238‐242, 2011.
 461.Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium‐derived relaxing factor. Nature 327: 524‐526, 1987.
 462.Pande A, Sarkar A, Ahmed I, Naveen Chandra G, Patil SK, Kundu CK, Arora R, Samanta A. Non‐invasive estimation of pulmonary vascular resistance in patients of pulmonary hypertension in congenital heart disease with unobstructed pulmonary flow. Ann Pediatr Cardiol 7: 92‐97, 2014.
 463.Park JE, Chen HH, Winer J, Houck KA, Ferrara N. Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt‐1 but not to Flk‐1/KDR. J Biol Chem 269: 25646‐25654, 1994.
 464.Partovian C, Adnot S, Raffestin B, Louzier V, Levame M, Mavier IM, Lemarchand P, Eddahibi S. Adenovirus‐mediated lung vascular endothelial growth factor overexpression protects against hypoxic pulmonary hypertension in rats. Am J Respir Cell Mol Biol 23: 762‐771, 2000.
 465.Patel N, Mills JF, Cheung MM. Assessment of right ventricular f unction using tissue Doppler imaging in infants with pulmonary hypertension. Neonatology 96: 193‐199; discussion 200‐192, 2009.
 466.Pearson JD. Normal endothelial cell function. Lupus 9: 183‐188, 2000.
 467.The Neonatal Inhaled Nitric Oxide Study Group (NINOS). Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. Pediatrics 99: 838‐845, 1997.
 468.Perros F, Montani D, Dorfmuller P, Durand‐Gasselin I, Tcherakian C, Le Pavec J, Mazmanian M, Fadel E, Mussot S, Mercier O, Herve P, Emilie D, Eddahibi S, Simonneau G, Souza R, Humbert M. Platelet‐derived growth factor expression and function in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 178: 81‐88, 2008.
 469.Peterson AL, Deatsman S, Frommelt MA, Mussatto K, Frommelt PC. Correlation of echocardiographic markers and therapy in persistent pulmonary hypertension of the newborn. Pediatr Cardiol 30: 160‐165, 2009.
 470.Pfarr N, Fischer C, Ehlken N, Becker‐Grunig T, Lopez‐Gonzalez V, Gorenflo M, Hager A, Hinderhofer K, Miera O, Nagel C, Schranz D, Grunig E. Hemodynamic and genetic analysis in children with idiopathic, heritable, and congenital heart disease associated pulmonary arterial hypertension. Respir Res 14: 3, 2013.
 471.Phosphodiesterase Type 5 (PDE5) Inhibitors. In: LiverTox: Clinical and Research Information on Drug‐Induced Liver Injury. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, 2012.
 472.Piao L, Fang YH, Parikh K, Ryan JJ, Toth PT, Archer SL. Cardiac glutaminolysis: A maladaptive cancer metabolism pathway in the right ventricle in pulmonary hypertension. J Mol Med (Berl) 91: 1185‐1197, 2013.
 473.Piao L, Fang YH, Parikh KS, Ryan JJ, D'Souza KM, Theccanat T, Toth PT, Pogoriler J, Paul J, Blaxall BC, Akhter SA, Archer SL. GRK2‐mediated inhibition of adrenergic and dopaminergic signaling in right ventricular hypertrophy: Therapeutic implications in pulmonary hypertension. Circulation 126: 2859‐2869, 2012.
 474.Ploegstra MJ, Arjaans S, Zijlstra WMH, Douwes JM, Vissia‐Kazemier TR, Roofthooft MTR, Hillege HL, Berger RMF. Clinical worsening as composite study end point in pediatric pulmonary arterial hypertension. Chest 148: 655‐666, 2015.
 475.Ploegstra MJ, Douwes JM, Roofthooft MT, Zijlstra WM, Hillege HL, Berger RM. Identification of treatment goals in paediatric pulmonary arterial hypertension. Eur Respir J 44: 1616‐1626, 2014.
 476.Ploegstra MJ, Roofthooft MT, Douwes JM, Bartelds B, Elzenga NJ, van de Weerd D, Hillege HL, Berger RM. Echocardiography in pediatric pulmonary arterial hypertension: Early study on assessing disease severity and predicting outcome. Circ Cardiovasc Imaging 8: e000878, 2015.
 477.Ploegstra MJ, Zijlstra WM, Douwes JM, Hillege HL, Berger RM. Prognostic factors in pediatric pulmonary arterial hypertension: A systematic review and meta‐analysis. Int J Cardiol 184: 198‐207, 2015.
 478.Pollock DM, Keith TL, Highsmith RF. Endothelin receptors and calcium signaling. FASEB J 9: 1196‐1204, 1995.
 479.Prabhakar NR, Semenza GL. Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia‐inducible factors 1 and 2. Physiol Rev 92: 967‐1003, 2012.
 480.Prins BA, Hu RM, Nazario B, Pedram A, Frank HJ, Weber MA, Levin ER. Prostaglandin E2 and prostacyclin inhibit the production and secretion of endothelin from cultured endothelial cells. J Biol Chem 269: 11938‐11944, 1994.
 481.Puchalski MD, Lozier JS, Bradley DJ, Minich LL, Tani LY. Electrocardiography in the diagnosis of right ventricular hypertrophy in children. Pediatrics 118: 1052‐1055, 2006.
 482.Pulido T, Adzerikho I, Channick RN, Delcroix M, Galie N, Ghofrani HA, Jansa P, Jing ZC, Le Brun FO, Mehta S, Mittelholzer CM, Perchenet L, Sastry BK, Sitbon O, Souza R, Torbicki A, Zeng X, Rubin LJ, Simonneau G, Investigators S. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 369: 809‐818, 2013.
 483.Putnam LR, Tsao K, Morini F, Lally PA, Miller CC, Lally KP, Harting MT, Congenital Diaphragmatic Hernia Study G. Evaluation of variability in inhaled nitric oxide use and pulmonary hypertension in patients with congenital diaphragmatic hernia. JAMA Pediatr 170: 1188‐1194, 2016.
 484.Qin W, Zhao B, Shi Y, Yao C, Jin L, Jin Y. BMPRII is a direct target of miR‐21. Acta Biochim Biophys Sin (Shanghai) 41: 618‐623, 2009.
 485.Rabinovitch M. Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest 122: 4306‐4313, 2012.
 486.Rabinovitch M, Gamble W, Nadas AS, Miettinen OS, Reid L. Rat pulmonary circulation after chronic hypoxia: Hemodynamic and structural features. Am J Physiol 236: H818‐H827, 1979.
 487.Rachdi I, Tougorti M, Daoud F, Aydi Z, Zoubeidi H, Ben Dhaou B, Boussema F. Pulmonary hypertension on systemic sclerosis‐lupus erythematosus overlap syndrome. Ann Cardiol Angeiol (Paris) 68: 221‐225, 2019.
 488.Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics 124: 1001‐1008, 2009.
 489.Ramirez RL 3rd, Perez VJ, Zamanian RT. Methamphetamine and the risk of pulmonary arterial hypertension. Curr Opin Pulm Med 24: 416‐424, 2018.
 490.Ramos RP, Arakaki JS, Barbosa P, Treptow E, Valois FM, Ferreira EV, Nery LE, Neder JA. Heart rate recovery in pulmonary arterial hypertension: Relationship with exercise capacity and prognosis. Am Heart J 163: 580‐588, 2012.
 491.Ranchoux B, Antigny F, Rucker‐Martin C, Hautefort A, Pechoux C, Bogaard HJ, Dorfmuller P, Remy S, Lecerf F, Plante S, Chat S, Fadel E, Houssaini A, Anegon I, Adnot S, Simonneau G, Humbert M, Cohen‐Kaminsky S, Perros F. Endothelial‐to‐mesenchymal transition in pulmonary hypertension. Circulation 131: 1006‐1018, 2015.
 492.Rapoport RM. Nitric oxide inhibition of endothelin‐1 release in the vasculature: In vivo relevance of in vitro findings. Hypertension 64: 908‐914, 2014.
 493.Raposo‐Sonnenfeld I, Otero‐Gonzalez I, Blanco‐Aparicio M, Ferrer‐Barba A, Medrano‐Lopez C. Treatment with sildenafil, bosentan, or both in children and young people with idiopathic pulmonary arterial hypertension and Eisenmenger's syndrome. Rev Esp Cardiol 60: 366‐372, 2007.
 494.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 97: 257‐262, 1998.
 495.Rasanen J, Wood DC, Weiner S, Ludomirski A, Huhta JC. Role of the pulmonary circulation in the distribution of human fetal cardiac output during the second half of pregnancy. Circulation 94: 1068‐1073, 1996.
 496.Raut MS, Maheshwari A. Inhaled nitric oxide, methemoglobinemia, and route of delivery. Saudi J Anaesth 11: 364, 2017.
 497.Reddy VM, Meyrick B, Wong J, Khoor A, Liddicoat JR, Hanley FL, Fineman JR. In utero placement of aortopulmonary shunts. A model of postnatal pulmonary hypertension with increased pulmonary blood flow in lambs. Circulation 92: 606‐613, 1995.
 498.Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium‐channel blockers on survival in primary pulmonary hypertension. N Engl J Med 327: 76‐81, 1992.
 499.Rich S, Seidlitz M, Dodin E, Osimani D, Judd D, Genthner D, McLaughlin V, Francis G. The short‐term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest 114: 787‐792, 1998.
 500.Richir MC, Ellger B, Teerlink T, Siroen MP, Visser M, Spreeuwenberg M, Girbes AR, van der Hoven B, van den Berghe G, Wilhelm AJ, de Vries TP, van Leeuwen PA. The effect of rosiglitazone on asymmetric dimethylarginine (ADMA) in critically ill patients. Pharmacol Res 60: 519‐524, 2009.
 501.Rodman DM, Reese K, Harral J, Fouty B, Wu S, West J, Hoedt‐Miller M, Tada Y, Li KX, Cool C, Fagan K, Cribbs L. Low‐voltage‐activated (T‐type) calcium channels control proliferation of human pulmonary artery myocytes. Circ Res 96: 864‐872, 2005.
 502.Rondelet B, Kerbaul F, Motte S, van Beneden R, Remmelink M, Brimioulle S, McEntee K, Wauthy P, Salmon I, Ketelslegers JM, Naeije R. Bosentan for the prevention of overcirculation‐induced experimental pulmonary arterial hypertension. Circulation 107: 1329‐1335, 2003.
 503.Rondelet B, Kerbaul F, Van Beneden R, Motte S, Fesler P, Hubloue I, Remmelink M, Brimioulle S, Salmon I, Ketelslegers JM, Naeije R. Signaling molecules in overcirculation‐induced pulmonary hypertension in piglets: Effects of sildenafil therapy. Circulation 110: 2220‐2225, 2004.
 504.Rondelet B, Kerbaul F, Vivian GF, Hubloue I, Huez S, Fesler P, Remmelink M, Brimiouille S, Salmon I, Naeije R. Sitaxsentan for the prevention of experimental shunt‐induced pulmonary hypertension. Pediatr Res 61: 284‐288, 2007.
 505.Rosenkranz S, Ghofrani HA, Beghetti M, Ivy D, Frey R, Fritsch A, Weimann G, Saleh S, Apitz C. Riociguat for pulmonary arterial hypertension associated with congenital heart disease. Heart 101: 1792‐1799, 2015.
 506.Rosenzweig EB, Abman SH, Adatia I, Beghetti M, Bonnet D, Haworth S, Ivy DD, Berger RMF. Paediatric pulmonary arterial hypertension: Updates on definition, classification, diagnostics and management. Eur Respir J 53: 1801916, 2019.
 507.Rosenzweig EB, Feinstein JA, Humpl T, Ivy DD. Pulmonary arterial hypertension in children: Diagnostic work‐up and challenges. Prog Pediatr Cardiol 27: 4‐11, 2009.
 508.Rosenzweig EB, Morse JH, Knowles JA, Chada KK, Khan AM, Roberts KE, McElroy JJ, Juskiw NK, Mallory NC, Rich S, Diamond B, Barst RJ. Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension. J Heart Lung Transplant 27: 668‐674, 2008.
 509.Rothman A, Sklansky MS, Lucas VW, Kashani IA, Shaughnessy RD, Channick RN, Auger WR, Fedullo PF, Smith CM, Kriett JM, Jamieson SW. Atrial septostomy as a bridge to lung transplantation in patients with severe pulmonary hypertension. Am J Cardiol 84: 682‐686, 1999.
 510.Roubliova X, Verbeken E, Wu J, Yamamoto H, Lerut T, Tibboel D, Deprest J. Pulmonary vascular morphology in a fetal rabbit model for congenital diaphragmatic hernia. J Pediatr Surg 39: 1066‐1072, 2004.
 511.Roubliova XI, Verbeken EK, Wu J, Vaast P, Jani J, Deprest JA. Effect of tracheal occlusion on peripheric pulmonary vessel muscularization in a fetal rabbit model for congenital diaphragmatic hernia. Am J Obstet Gynecol 191: 830‐836, 2004.
 512.Ruan H, Zhang Y, Liu R, Yang X. The acute effects of 30 mg vs 60 mg of intravenous Fasudil on patients with congenital heart defects and severe pulmonary arterial hypertension. Congenit Heart Dis 14: 645‐650, 2019.
 513.Ruan HY, Zhang YG, Liu R. Acute effects of intravenous fasudil with different dosage on patients with congenital heart defects and severe pulmonary arterial hypertension. Zhonghua Yi Xue Za Zhi 98: 678‐681, 2018.
 514.Rubin LJ, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, Keogh A, Langleben D, Fritsch A, Menezes F, Davie N, Ghofrani HA. Riociguat for the treatment of pulmonary arterial hypertension: A long‐term extension study (PATENT‐2). Eur Respir J 45: 1303‐1313, 2015.
 515.Rudarakanchana N, Flanagan JA, Chen H, Upton PD, Machado R, Patel D, Trembath RC, Morrell NW. Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension. Hum Mol Genet 11: 1517‐1525, 2002.
 516.Rudolph AM, Yuan S. Response of the pulmonary vasculature to hypoxia and H+ ion concentration changes. J Clin Invest 45: 399‐411, 1966.
 517.Ruiz‐Cano MJ, Escribano P, Alonso R, Delgado J, Carreira P, Velazquez T, Sanchez MA, Saenz de la Calzada C. Comparison of baseline characteristics and survival between patients with idiopathic and connective tissue disease‐related pulmonary arterial hypertension. J Heart Lung Transplant 28: 621‐627, 2009.
 518.Ryan JJ, Huston J, Kutty S, Hatton ND, Bowman L, Tian L, Herr JE, Johri AM, Archer SL. Right ventricular adaptation and failure in pulmonary arterial hypertension. Can J Cardiol 31: 391‐406, 2015.
 519.Sabri MR, Beheshtian E. Comparison of the therapeutic and side effects of tadalafil and sildenafil in children and adolescents with pulmonary arterial hypertension. Pediatr Cardiol 35: 699‐704, 2014.
 520.Sadiq HF, Mantych G, Benawra RS, Devaskar UP, Hocker JR. Inhaled nitric oxide in the treatment of moderate persistent pulmonary hypertension of the newborn: A randomized controlled, multicenter trial. J Perinatol 23: 98‐103, 2003.
 521.Said S, Porres‐Aguilar M, Porres‐Munoz M, Mukherjee D. Eisenmenger syndrome: Recent advances in pharmacotherapy. Cardiovasc Hematol Agents Med Chem 11: 289‐296, 2013.
 522.Sandoval J, Gaspar J, Pena H, Santos LE, Cordova J, del Valle K, Rodriguez A, Pulido T. Effect of atrial septostomy on the survival of patients with severe pulmonary arterial hypertension. Eur Respir J 38: 1343‐1348, 2011.
 523.Sandoval J, Santos LE, Cordova J, Pulido T, Gutierrez G, Bautista E, Martinez Guerra ML, Pena H, Broberg CS. Does anticoagulation in Eisenmenger syndrome impact long‐term survival? Congenit Heart Dis 7: 268‐276, 2012.
 524.Sato T, Tsujino I, Ohira H, Oyama‐Manabe N, Yamada A, Ito YM, Goto C, Watanabe T, Sakaue S, Nishimura M. Validation study on the accuracy of echocardiographic measurements of right ventricular systolic function in pulmonary hypertension. J Am Soc Echocardiogr 25: 280‐286, 2012.
 525.Sawada H, Mitani Y, Nakayama T, Fukushima H, Kogaki S, Igarashi T, Ichida F, Ono Y, Nakanishi T, Doi S, Ishikawa S, Matsushima M, Yamada O, Saji T. Detection of pediatric pulmonary arterial hypertension by school electrocardiography mass screening. Am J Respir Crit Care Med 199: 1397‐1406, 2019.
 526.Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115: 2811‐2821, 2005.
 527.Schlapbach LJ, Horton SB, Long DA, Beca J, Erickson S, Festa M, d'Udekem Y, Alphonso N, Winlaw D, Johnson K, Delzoppo C, van Loon K, Gannon B, Fooken J, Blumenthal A, Young P, Jones M, Butt W, Schibler A, Nitric Study Group tA, New Zealand Intensive Care Society Clinical Trials Group tPCCRg, and the APSG. Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): A randomised controlled trial. BMJ Open 9: e026664, 2019.
 528.Schmidt B, Whyte RK. Oxygen saturation target ranges and alarm settings in the NICU: What have we learnt from the neonatal oxygenation prospective meta‐analysis (NeOProM)? Semin Fetal Neonatal Med 25: 101080, 2020.
 529.Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C, Rabi Y, Solimano A, Roberts RS, Canadian Oxygen Trial G. Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: A randomized clinical trial. JAMA 309: 2111‐2120, 2013.
 530.Schreiber MD, Gin‐Mestan K, Marks JD, Huo D, Lee G, Srisuparp P. Inhaled nitric oxide in premature infants with the respiratory distress syndrome. N Engl J Med 349: 2099‐2107, 2003.
 531.Schulze‐Neick I, Hartenstein P, Li J, Stiller B, Nagdyman N, Hubler M, Butrous G, Petros A, Lange P, Redington AN. Intravenous sildenafil is a potent pulmonary vasodilator in children with congenital heart disease. Circulation 108 (Suppl 1): II167‐II173, 2003.
 532.Schwenke DO, Pearson JT, Sonobe T, Ishibashi‐Ueda H, Shimouchi A, Kangawa K, Umetani K, Shirai M. Role of Rho‐kinase signaling and endothelial dysfunction in modulating blood flow distribution in pulmonary hypertension. J Appl Physiol (1985) 110: 901‐908, 2011.
 533.Seghezzi G, Patel S, Ren CJ, Gualandris A, Pintucci G, Robbins ES, Shapiro RL, Galloway AC, Rifkin DB, Mignatti P. Fibroblast growth factor‐2 (FGF‐2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: An autocrine mechanism contributing to angiogenesis. J Cell Biol 141: 1659‐1673, 1998.
 534.Seta F, Rahmani M, Turner PV, Funk CD. Pulmonary oxidative stress is increased in cyclooxygenase‐2 knockdown mice with mild pulmonary hypertension induced by monocrotaline. PLoS One 6: e23439, 2011.
 535.Shaul PW, Yuhanna IS, German Z, Chen Z, Steinhorn RH, Morin FC 3rd. Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension. Am J Physiol 272: L1005‐L1012, 1997.
 536.Shimoda LA, Laurie SS. Vascular remodeling in pulmonary hypertension. J Mol Med (Berl) 91: 297‐309, 2013.
 537.Shimoda LA, Sham JS, Shimoda TH, Sylvester JT. L‐type Ca(2+) channels, resting [Ca(2+)](i), and ET‐1‐induced responses in chronically hypoxic pulmonary myocytes. Am J Physiol Lung Cell Mol Physiol 279: L884‐L894, 2000.
 538.Shivanna B, Gowda S, Welty SE, Barrington KJ, Pammi M. Prostanoids and their analogues for the treatment of pulmonary hypertension in neonates. Cochrane Database Syst Rev 10: CD012963, 2019.
 539.Siebert JR, Haas JE, Beckwith JB. Left ventricular hypoplasia in congenital diaphragmatic hernia. J Pediatr Surg 19: 567‐571, 1984.
 540.Siehr SL, Ivy DD, Miller‐Reed K, Ogawa M, Rosenthal DN, Feinstein JA. Children with pulmonary arterial hypertension and prostanoid therapy: Long‐term hemodynamics. J Heart Lung Transplant 32: 546‐552, 2013.
 541.Simonneau G, D'Armini AM, Ghofrani HA, Grimminger F, Hoeper MM, Jansa P, Kim NH, Wang C, Wilkins MR, Fritsch A, Davie N, Colorado P, Mayer E. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: A long‐term extension study (CHEST‐2). Eur Respir J 45: 1293‐1302, 2015.
 542.Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, Gibbs S, Lebrec D, Speich R, Beghetti M, Rich S, Fishman A. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 43: 5S‐12S, 2004.
 543.Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF, Olschewski H, Robbins IM, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 62: D34‐D41, 2013.
 544.Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, Williams PG, Souza R. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 53: 1801913, 2019.
 545.Simonneau G, Rubin LJ, Galie N, Barst RJ, Fleming TR, Frost A, Engel P, Kramer MR, Serdarevic‐Pehar M, Layton GR, Sitbon O, Badesch DB, Group PS. Long‐term sildenafil added to intravenous epoprostenol in patients with pulmonary arterial hypertension. J Heart Lung Transplant 33: 689‐697, 2014.
 546.Singh RK, Richmond ME, Zuckerman WA, Lee TM, Giblin TB, Rodriguez R, Chen JM, Addonizio LJ. The use of oral sildenafil for management of right ventricular dysfunction after pediatric heart transplantation. Am J Transplant 14: 453‐458, 2014.
 547.Sitbon O, Humbert M, Jagot JL, Taravella O, Fartoukh M, Parent F, Herve P, Simonneau G. Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium‐channel blockers in primary pulmonary hypertension. Eur Respir J 12: 265‐270, 1998.
 548.Sitbon O, Humbert M, Jais X, Ioos V, Hamid AM, Provencher S, Garcia G, Parent F, Herve P, Simonneau G. Long‐term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 111: 3105‐3111, 2005.
 549.Smadja DM, Gaussem P, Mauge L, Israel‐Biet D, Dignat‐George F, Peyrard S, Agnoletti G, Vouhe PR, Bonnet D, Levy M. Circulating endothelial cells: A new candidate biomarker of irreversible pulmonary hypertension secondary to congenital heart disease. Circulation 119: 374‐381, 2009.
 550.Smadja DM, Gaussem P, Mauge L, Lacroix R, Gandrille S, Remones V, Peyrard S, Sabatier F, Bonnet D, Levy M. Comparison of endothelial biomarkers according to reversibility of pulmonary hypertension secondary to congenital heart disease. Pediatr Cardiol 31: 657‐662, 2010.
 551.Smith G, Reyes JT, Russell JL, Humpl T. Safety of maximal cardiopulmonary exercise testing in pediatric patients with pulmonary hypertension. Chest 135: 1209‐1214, 2009.
 552.Smith KA, Voiriot G, Tang H, Fraidenburg DR, Song S, Yamamura H, Yamamura A, Guo Q, Wan J, Pohl NM, Tauseef M, Bodmer R, Ocorr K, Thistlethwaite PA, Haddad GG, Powell FL, Makino A, Mehta D, Yuan JX. Notch activation of Ca(2+) signaling in the development of hypoxic pulmonary vasoconstriction and pulmonary hypertension. Am J Respir Cell Mol Biol 53: 355‐367, 2015.
 553.Soma S, Takahashi H, Muramatsu M, Oka M, Fukuchi Y. Localization and distribution of endothelin receptor subtypes in pulmonary vasculature of normal and hypoxia‐exposed rats. Am J Respir Cell Mol Biol 20: 620‐630, 1999.
 554.Somlyo AP, Somlyo AV. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: Modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83: 1325‐1358, 2003.
 555.Souza R, Channick RN, Delcroix M, Galie N, Ghofrani HA, Jansa P, Le Brun FO, Mehta S, Perchenet L, Pulido T, Sastry BKS, Sitbon O, Torbicki A, Rubin LJ, Simonneau G. Association between six‐minute walk distance and long‐term outcomes in patients with pulmonary arterial hypertension: Data from the randomized SERAPHIN trial. PLoS One 13: e0193226, 2018.
 556.Spaggiari E, Stirnemann JJ, Sonigo P, Khen‐Dunlop N, De Saint BL, Ville Y. Prenatal prediction of pulmonary arterial hypertension in congenital diaphragmatic hernia. Ultrasound Obstet Gynecol 45: 572‐577, 2015.
 557.Spiekerkoetter E, Sung YK, Sudheendra D, Scott V, Del Rosario P, Bill M, Haddad F, Long‐Boyle J, Hedlin H, Zamanian RT. Randomised placebo‐controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension. Eur Respir J 50: 1602449, 2017.
 558.Spiekerkoetter E, Tian X, Cai J, Hopper RK, Sudheendra D, Li CG, El‐Bizri N, Sawada H, Haghighat R, Chan R, Haghighat L, de Jesus PV, Wang L, Reddy S, Zhao M, Bernstein D, Solow‐Cordero DE, Beachy PA, Wandless TJ, Ten Dijke P, Rabinovitch M. FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension. J Clin Invest 123: 3600‐3613, 2013.
 559.Spreemann T, Bertram H, Happel CM, Kozlik‐Feldmann R, Hansmann G. First‐in‐child use of the oral soluble guanylate cyclase stimulator riociguat in pulmonary arterial hypertension. Pulm Circ 8: 2045893217743123, 2018.
 560.Srisuparp P, Heitschmidt M, Schreiber MD. Inhaled nitric oxide therapy in premature infants with mild to moderate respiratory distress syndrome. J Med Assoc Thai 85 (Suppl 2): S469‐S478, 2002.
 561.Stacher E, Graham BB, Hunt JM, Gandjeva A, Groshong SD, McLaughlin VV, Jessup M, Grizzle WE, Aldred MA, Cool CD, Tuder RM. Modern age pathology of pulmonary arterial hypertension. Am J Respir Crit Care Med 186: 261‐272, 2012.
 562.Steinhorn RH, Fineman J, Kusic‐Pajic A, Cornelisse P, Gehin M, Nowbakht P, Pierce CM, Beghetti M, investigators F‐s. Bosentan as adjunctive therapy for persistent pulmonary hypertension of the newborn: Results of the randomized multicenter placebo‐controlled exploratory trial. J Pediatr 177: 90‐96 e93, 2016.
 563.Steinhorn RH, Kinsella JP, Pierce C, Butrous G, Dilleen M, Oakes M, Wessel DL. Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension. J Pediatr 155: 841‐847 e841, 2009.
 564.Steinhorn RH, Lakshminrusimha S. Oxygen and pulmonary vasodilation: The role of oxidative and nitrosative stress. Semin Fetal Neonatal Med 25: 101083, 2020.
 565.Steinhorn RH, Morin FC 3rd, Fineman JR. Models of persistent pulmonary hypertension of the newborn (PPHN) and the role of cyclic guanosine monophosphate (GMP) in pulmonary vasorelaxation. Semin Perinatol 21: 393‐408, 1997.
 566.Stenmark KR, Durmowicz AG, Roby JD, Mecham RP, Parks WC. Persistence of the fetal pattern of tropoelastin gene expression in severe neonatal bovine pulmonary hypertension. J Clin Invest 93: 1234‐1242, 1994.
 567.Stenmark KR, Frid M, Perros F. Endothelial‐to‐mesenchymal transition: An evolving paradigm and a promising therapeutic target in PAH. Circulation 133: 1734‐1737, 2016.
 568.Stenmark KR, Meyrick B, Galie N, Mooi WJ, McMurtry IF. Animal models of pulmonary arterial hypertension: The hope for etiological discovery and pharmacological cure. Am J Physiol Lung Cell Mol Physiol 297: L1013‐L1032, 2009.
 569.Stenmark KR, Yeager ME, El Kasmi KC, Nozik‐Grayck E, Gerasimovskaya EV, Li M, Riddle SR, Frid MG. The adventitia: Essential regulator of vascular wall structure and function. Annu Rev Physiol 75: 23‐47, 2013.
 570.Su BH, Peng CT, Tsai CH. Persistent pulmonary hypertension of the newborn: Echocardiographic assessment. Acta Paediatr Taiwan 42: 218‐223, 2001.
 571.Su PH, Chen JY. Inhaled nitric oxide in the management of preterm infants with severe respiratory failure. J Perinatol 28: 112‐116, 2008.
 572.Subhedar NV, Ryan SW, Shaw NJ. Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants. Arch Dis Child Fetal Neonatal Ed 77: F185‐F190, 1997.
 573.Sud N, Wells SM, Sharma S, Wiseman DA, Wilham J, Black SM. Asymmetric dimethylarginine inhibits HSP90 activity in pulmonary arterial endothelial cells: Role of mitochondrial dysfunction. Am J Physiol Cell Physiol 294: C1407‐C1418, 2008.
 574.Sundaram SM, Chung L. An update on systemic sclerosis‐associated pulmonary arterial hypertension: A review of the current literature. Curr Rheumatol Rep 20: 10, 2018.
 575.Swier NL, Richards B, Cua CL, Lynch SK, Yin H, Nelin LD, Smith CV, Backes CH. Pulmonary vein stenosis in neonates with severe bronchopulmonary dysplasia. Am J Perinatol 33: 671‐677, 2016.
 576.Szafranski P, Gambin T, Dharmadhikari AV, Akdemir KC, Jhangiani SN, Schuette J, Godiwala N, Yatsenko SA, Sebastian J, Madan‐Khetarpal S, Surti U, Abellar RG, Bateman DA, Wilson AL, Markham MH, Slamon J, Santos‐Simarro F, Palomares M, Nevado J, Lapunzina P, Chung BH, Wong WL, Chu YWY, Mok GTK, Kerem E, Reiter J, Ambalavanan N, Anderson SA, Kelly DR, Shieh J, Rosenthal TC, Scheible K, Steiner L, Iqbal MA, McKinnon ML, Hamilton SJ, Schlade‐Bartusiak K, English D, Hendson G, Roeder ER, DeNapoli TS, Littlejohn RO, Wolff DJ, Wagner CL, Yeung A, Francis D, Fiorino EK, Edelman M, Fox J, Hayes DA, Janssens S, De Baere E, Menten B, Loccufier A, Vanwalleghem L, Moerman P, Sznajer Y, Lay AS, Kussmann JL, Chawla J, Payton DJ, Phillips GE, Brosens E, Tibboel D, de Klein A, Maystadt I, Fisher R, Sebire N, Male A, Chopra M, Pinner J, Malcolm G, Peters G, Arbuckle S, Lees M, Mead Z, Quarrell O, Sayers R, Owens M, Shaw‐Smith C, Lioy J, McKay E, de Leeuw N, Feenstra I, Spruijt L, Elmslie F, Thiruchelvam T, Bacino CA, Langston C, Lupski JR, Sen P, Popek E, Stankiewicz P. Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins. Hum Genet 135: 569‐586, 2016.
 577.Tajsic T, Morrell NW. Smooth muscle cell hypertrophy, proliferation, migration and apoptosis in pulmonary hypertension. Compr Physiol 1: 295‐317, 2011.
 578.Takano H, Komuro I. Peroxisome proliferator‐activated receptor gamma and cardiovascular diseases. Circ J 73: 214‐220, 2009.
 579.Takatsuki S, Calderbank M, Ivy DD. Initial experience with tadalafil in pediatric pulmonary arterial hypertension. Pediatr Cardiol 33: 683‐688, 2012.
 580.Takatsuki S, Rosenzweig EB, Zuckerman W, Brady D, Calderbank M, Ivy DD. Clinical safety, pharmacokinetics, and efficacy of ambrisentan therapy in children with pulmonary arterial hypertension. Pediatr Pulmonol 48: 27‐34, 2013.
 581.Takemoto M, Sun J, Hiroki J, Shimokawa H, Liao JK. Rho‐kinase mediates hypoxia‐induced downregulation of endothelial nitric oxide synthase. Circulation 106: 57‐62, 2002.
 582.Tal A, Leiberman A, Margulis G, Sofer S. Ventricular dysfunction in children with obstructive sleep apnea: Radionuclide assessment. Pediatr Pulmonol 4: 139‐143, 1988.
 583.Taraseviciene‐Stewart L, Kasahara Y, Alger L, Hirth P, Mc Mahon G, Waltenberger J, Voelkel NF, Tuder RM. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death‐dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J 15: 427‐438, 2001.
 584.Taylor CJ, Derrick G, McEwan A, Haworth SG, Sury MR. Risk of cardiac catheterization under anaesthesia in children with pulmonary hypertension. Br J Anaesth 98: 657‐661, 2007.
 585.ten Freyhaus H, Dagnell M, Leuchs M, Vantler M, Berghausen EM, Caglayan E, Weissmann N, Dahal BK, Schermuly RT, Ostman A, Kappert K, Rosenkranz S. Hypoxia enhances platelet‐derived growth factor signaling in the pulmonary vasculature by down‐regulation of protein tyrosine phosphatases. Am J Respir Crit Care Med 183: 1092‐1102, 2011.
 586.Teng RJ, Du J, Afolayan AJ, Eis A, Shi Y, Konduri GG. AMP kinase activation improves angiogenesis in pulmonary artery endothelial cells with in utero pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 304: L29‐L42, 2013.
 587.Teng RJ, Eis A, Bakhutashvili I, Arul N, Konduri GG. Increased superoxide production contributes to the impaired angiogenesis of fetal pulmonary arteries with in utero pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 297: L184‐L195, 2009.
 588.Thebaud B, Abman SH. Bronchopulmonary dysplasia: Where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. Am J Respir Crit Care Med 175: 978‐985, 2007.
 589.Thenappan T, Chan SY, Weir EK. Role of extracellular matrix in the pathogenesis of pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 315: H1322‐H1331, 2018.
 590.Thomas CA, Valentine K. Utility of routine methemoglobin laboratory assays in critically ill pediatric subjects receiving inhaled nitric oxide. J Crit Care 48: 63‐65, 2018.
 591.Thomson JR, Machado RD, Pauciulo MW, Morgan NV, Humbert M, Elliott GC, Ward K, Yacoub M, Mikhail G, Rogers P, Newman J, Wheeler L, Higenbottam T, Gibbs JS, Egan J, Crozier A, Peacock A, Allcock R, Corris P, Loyd JE, Trembath RC, Nichols WC. Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR‐II, a receptor member of the TGF‐beta family. J Med Genet 37: 741‐745, 2000.
 592.Tissot C, Ivy DD, Beghetti M. Medical therapy for pediatric pulmonary arterial hypertension. J Pediatr 157: 528‐532, 2010.
 593.Tonelli AR, Alnuaimat H, Mubarak K. Pulmonary vasodilator testing and use of calcium channel blockers in pulmonary arterial hypertension. Respir Med 104: 481‐496, 2010.
 594.Tourneux P, Chester M, Grover T, Abman SH. Fasudil inhibits the myogenic response in the fetal pulmonary circulation. Am J Physiol Heart Circ Physiol 295: H1505‐H1513, 2008.
 595.Tsai IC, Tsai WL, Wang KY, Chen MC, Liang KW, Tsai HY, Liao WC. Comprehensive MDCT evaluation of patients with pulmonary hypertension: Diagnosing underlying causes with the updated Dana Point 2008 classification. AJR Am J Roentgenol 197: W471‐W481, 2011.
 596.Tuder RM. Pulmonary vascular remodeling in pulmonary hypertension. Cell Tissue Res 367: 643‐649, 2017.
 597.Tuder RM, Chacon M, Alger L, Wang J, Taraseviciene‐Stewart L, Kasahara Y, Cool CD, Bishop AE, Geraci M, Semenza GL, Yacoub M, Polak JM, Voelkel NF. Expression of angiogenesis‐related molecules in plexiform lesions in severe pulmonary hypertension: Evidence for a process of disordered angiogenesis. J Pathol 195: 367‐374, 2001.
 598.Tuder RM, Cool CD, Geraci MW, Wang J, Abman SH, Wright L, Badesch D, Voelkel NF. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 159: 1925‐1932, 1999.
 599.Tuder RM, Flook BE, Voelkel NF. Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. J Clin Invest 95: 1798‐1807, 1995.
 600.Tuder RM, Groves B, Badesch DB, Voelkel NF. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 144: 275‐285, 1994.
 601.Tunks RD, Barker PC, Benjamin DK Jr, Cohen‐Wolkowiez M, Fleming GA, Laughon M, Li JS, Hill KD. Sildenafil exposure and hemodynamic effect after Fontan surgery. Pediatr Crit Care Med 15: 28‐34, 2014.
 602.Uslu S, Kumtepe S, Bulbul A, Comert S, Bolat F, Nuhoglu A. A comparison of magnesium sulphate and sildenafil in the treatment of the newborns with persistent pulmonary hypertension: A randomized controlled trial. J Trop Pediatr 57: 245‐250, 2011.
 603.van Loenhout RB, Tibboel D, Post M, Keijzer R. Congenital diaphragmatic hernia: Comparison of animal models and relevance to the human situation. Neonatology 96: 137‐149, 2009.
 604.van Loon RL, Roofthooft MT, Hillege HL, ten Harkel AD, van Osch‐Gevers M, Delhaas T, Kapusta L, Strengers JL, Rammeloo L, Clur SA, Mulder BJ, Berger RM. Pediatric pulmonary hypertension in the Netherlands: Epidemiology and characterization during the period 1991 to 2005. Circulation 124: 1755‐1764, 2011.
 605.Van Meurs KP, Wright LL, Ehrenkranz RA, Lemons JA, Ball MB, Poole WK, Perritt R, Higgins RD, Oh W, Hudak ML, Laptook AR, Shankaran S, Finer NN, Carlo WA, Kennedy KA, Fridriksson JH, Steinhorn RH, Sokol GM, Konduri GG, Aschner JL, Stoll BJ, D'Angio CT, Stevenson DK. Preemie Inhaled Nitric Oxide Study. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med 353: 13‐22, 2005.
 606.Vandecasteele E, Drieghe B, Melsens K, Thevissen K, De Pauw M, Deschepper E, Decuman S, Bonroy C, Piette Y, De Keyser F, Brusselle G, Smith V. Screening for pulmonary arterial hypertension in an unselected prospective systemic sclerosis cohort. Eur Respir J 49: 1602275, 2017.
 607.Vattulainen‐Collanus S, Akinrinade O, Li M, Koskenvuo M, Li CG, Rao SP, de Jesus Perez V, Yuan K, Sawada H, Koskenvuo JW, Alvira C, Rabinovitch M, Alastalo TP. Loss of PPARgamma in endothelial cells leads to impaired angiogenesis. J Cell Sci 129: 693‐705, 2016.
 608.Veit F, Pak O, Egemnazarov B, Roth M, Kosanovic D, Seimetz M, Sommer N, Ghofrani HA, Seeger W, Grimminger F, Brandes RP, Schermuly RT, Weissmann N. Function of NADPH oxidase 1 in pulmonary arterial smooth muscle cells after monocrotaline‐induced pulmonary vascular remodeling. Antioxid Redox Signal 19: 2213‐2231, 2013.
 609.Viola N, Alghamdi AA, Perrin DG, Wilson GJ, Coles JG, Caldarone CA. Primary pulmonary vein stenosis: The impact of sutureless repair on survival. J Thorac Cardiovasc Surg 142: 344‐350, 2011.
 610.Vitali SH, Hansmann G, Rose C, Fernandez‐Gonzalez A, Scheid A, Mitsialis SA, Kourembanas S. The Sugen 5416/hypoxia mouse model of pulmonary hypertension revisited: Long‐term follow‐up. Pulm Circ 4: 619‐629, 2014.
 611.Vlahos AP, Feinstein JA, Schiller NB, Silverman NH. Extension of Doppler‐derived echocardiographic measures of pulmonary vascular resistance to patients with moderate or severe pulmonary vascular disease. J Am Soc Echocardiogr 21: 711‐714, 2008.
 612.Volkow ND, Fowler JS, Wang GJ, Shumay E, Telang F, Thanos PK, Alexoff D. Distribution and pharmacokinetics of methamphetamine in the human body: Clinical implications. PLoS One 5: e15269, 2010.
 613.Walsh‐Sukys MC, Tyson JE, Wright LL, Bauer CR, Korones SB, Stevenson DK, Verter J, Stoll BJ, Lemons JA, Papile LA, Shankaran S, Donovan EF, Oh W, Ehrenkranz RA, Fanaroff AA. Persistent pulmonary hypertension of the newborn in the era before nitric oxide: Practice variation and outcomes. Pediatrics 105: 14‐20, 2000.
 614.Wan J, Yamamura A, Zimnicka AM, Voiriot G, Smith KA, Tang H, Ayon RJ, Choudhury MS, Ko EA, Wang J, Wang C, Makino A, Yuan JX. Chronic hypoxia selectively enhances L‐ and T‐type voltage‐dependent Ca2+ channel activity in pulmonary artery by upregulating Cav1.2 and Cav3.2. Am J Physiol Lung Cell Mol Physiol 305: L154‐L164, 2013.
 615.Wang H, Jafri A, Martin RJ, Nnanabu J, Farver C, Prakash YS, MacFarlane PM. Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway. Am J Physiol Lung Cell Mol Physiol 307: L295‐L301, 2014.
 616.Wang J, Prakasa K, Bomma C, Tandri H, Dalal D, James C, Tichnell C, Corretti M, Bluemke D, Calkins H, Abraham TP. Comparison of novel echocardiographic parameters of right ventricular function with ejection fraction by cardiac magnetic resonance. J Am Soc Echocardiogr 20: 1058‐1064, 2007.
 617.Wang J, Weigand L, Lu W, Sylvester JT, Semenza GL, Shimoda LA. Hypoxia inducible factor 1 mediates hypoxia‐induced TRPC expression and elevated intracellular Ca2+ in pulmonary arterial smooth muscle cells. Circ Res 98: 1528‐1537, 2006.
 618.Wang Y, Chen S, Du J. Bosentan for treatment of pediatric idiopathic pulmonary arterial hypertension: State‐of‐the‐art. Front Pediatr 7: 302, 2019.
 619.Wedgwood S, Black SM. Induction of apoptosis in fetal pulmonary arterial smooth muscle cells by a combined superoxide dismutase/catalase mimetic. Am J Physiol Lung Cell Mol Physiol 285: L305‐L312, 2003.
 620.Wedgwood S, Black SM. Role of reactive oxygen species in vascular remodeling associated with pulmonary hypertension. Antioxid Redox Signal 5: 759‐769, 2003.
 621.Wedgwood S, Dettman RW, Black SM. ET‐1 stimulates pulmonary arterial smooth muscle cell proliferation via induction of reactive oxygen species. Am J Physiol Lung Cell Mol Physiol 281: L1058‐L1067, 2001.
 622.Wedgwood S, Devol JM, Grobe A, Benavidez E, Azakie A, Fineman JR, Black SM. Fibroblast growth factor‐2 expression is altered in lambs with increased pulmonary blood flow and pulmonary hypertension. Pediatr Res 61: 32‐36, 2007.
 623.Wedgwood S, Lakshminrusimha S, Fukai T, Russell JA, Schumacker PT, Steinhorn RH. Hydrogen peroxide regulates extracellular superoxide dismutase activity and expression in neonatal pulmonary hypertension. Antioxid Redox Signal 15: 1497‐1506, 2011.
 624.Wedgwood S, Lakshminrusimha S, Schumacker PT, Steinhorn RH. Hypoxia inducible factor signaling and experimental persistent pulmonary hypertension of the newborn. Front Pharmacol 6: 47, 2015.
 625.Wedgwood S, Steinhorn RH. Role of reactive oxygen species in neonatal pulmonary vascular disease. Antioxid Redox Signal 21: 1926‐1942, 2014.
 626.Wedgwood S, Steinhorn RH, Bunderson M, Wilham J, Lakshminrusimha S, Brennan LA, Black SM. Increased hydrogen peroxide downregulates soluble guanylate cyclase in the lungs of lambs with persistent pulmonary hypertension of the newborn. Am J Physiol Lung Cell Mol Physiol 289: L660‐L666, 2005.
 627.Wei QF, Pan XN, Li Y, Feng L, Yao LP, Liu GL, Meng DH, Xu J, Guo XF, Liu XZ. Efficacy of inhaled nitric oxide in premature infants with hypoxic respiratory failure. Zhongguo Dang Dai Er Ke Za Zhi 16: 805‐809, 2014.
 628.Weigand L, Sylvester JT, Shimoda LA. Mechanisms of endothelin‐1‐induced contraction in pulmonary arteries from chronically hypoxic rats. Am J Physiol Lung Cell Mol Physiol 290: L284‐L290, 2006.
 629.Weir EK, Archer SL. The mechanism of acute hypoxic pulmonary vasoconstriction: The tale of two channels. FASEB J 9: 183‐189, 1995.
 630.Weismann CG, Asnes JD, Bazzy‐Asaad A, Tolomeo C, Ehrenkranz RA, Bizzarro MJ. Pulmonary hypertension in preterm infants: Results of a prospective screening program. J Perinatol 37: 572‐577, 2017.
 631.Welch CL, Austin ED, Chung WK. Genes that drive the pathobiology of pediatric pulmonary arterial hypertension. Pediatr Pulmonol, 2020. DOI: 10.1002/ppul.24637.
 632.Wensel R, Opitz CF, Anker SD, Winkler J, Hoffken G, Kleber FX, Sharma R, Hummel M, Hetzer R, Ewert R. Assessment of survival in patients with primary pulmonary hypertension: Importance of cardiopulmonary exercise testing. Circulation 106: 319‐324, 2002.
 633.Wessel DL, Adatia I, Van Marter LJ, Thompson JE, Kane JW, Stark AR, Kourembanas S. Improved oxygenation in a randomized trial of inhaled nitric oxide for persistent pulmonary hypertension of the newborn. Pediatrics 100: E7, 1997.
 634.West J, Austin E, Fessel JP, Loyd J, Hamid R. Rescuing the BMPR2 signaling axis in pulmonary arterial hypertension. Drug Discov Today 19: 1241‐1245, 2014.
 635.Wynn J, Krishnan U, Aspelund G, Zhang Y, Duong J, Stolar CJ, Hahn E, Pietsch J, Chung D, Moore D, Austin E, Mychaliska G, Gajarski R, Foong YL, Michelfelder E, Potolka D, Bucher B, Warner B, Grady M, Azarow K, Fletcher SE, Kutty S, Delaney J, Crombleholme T, Rosenzweig E, Chung W, Arkovitz MS. Outcomes of congenital diaphragmatic hernia in the modern era of management. J Pediatr 163: 114‐119 e111, 2013.
 636.Xie X, Wang G, Zhang D, Zhang Y, Zhu Y, Li F, Li S, Li M. Activation of peroxisome proliferator‐activated receptor gamma ameliorates monocrotaline‐induced pulmonary arterial hypertension in rats. Biomed Rep 3: 537‐542, 2015.
 637.Xing Y, Zheng X, Li G, Liao L, Cao W, Xing H, Shen T, Sun L, Yang B, Zhu D. MicroRNA‐30c contributes to the development of hypoxia pulmonary hypertension by inhibiting platelet‐derived growth factor receptor beta expression. Int J Biochem Cell Biol 64: 155‐166, 2015.
 638.Yamamura H, Yamamura A, Ko EA, Pohl NM, Smith KA, Zeifman A, Powell FL, Thistlethwaite PA, Yuan JX. Activation of Notch signaling by short‐term treatment with Jagged‐1 enhances store‐operated Ca(2+) entry in human pulmonary arterial smooth muscle cells. Am J Physiol Cell Physiol 306: C871‐C878, 2014.
 639.Yamazaki H, Kobayashi N, Taketsuna M, Tajima K, Suzuki N, Murakami M. Safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension: A sub‐group analysis based on Japan post‐marketing surveillance. Curr Med Res Opin 33: 2241‐2249, 2017.
 640.Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411‐415, 1988.
 641.Yang S, Banerjee S, Freitas A, Cui H, Xie N, Abraham E, Liu G. miR‐21 regulates chronic hypoxia‐induced pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol 302: L521‐L529, 2012.
 642.Yang X, Long L, Southwood M, Rudarakanchana N, Upton PD, Jeffery TK, Atkinson C, Chen H, Trembath RC, Morrell NW. Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Circ Res 96: 1053‐1063, 2005.
 643.Ye CL, Rabinovitch M. Inhibition of elastolysis by SC‐37698 reduces development and progression of monocrotaline pulmonary hypertension. Am J Physiol 261: H1255‐H1267, 1991.
 644.Yee M, White RJ, Awad HA, Bates WA, McGrath‐Morrow SA, O'Reilly MA. Neonatal hyperoxia causes pulmonary vascular disease and shortens life span in aging mice. Am J Pathol 178: 2601‐2610, 2011.
 645.Yilmaz O, Kahveci H, Zeybek C, Ciftel M, Kilic O. Inhaled iloprost in preterm infants with severe respiratory distress syndrome and pulmonary hypertension. Am J Perinatol 31: 321‐326, 2014.
 646.Yu AY, Shimoda LA, Iyer NV, Huso DL, Sun X, McWilliams R, Beaty T, Sham JS, Wiener CM, Sylvester JT, Semenza GL. Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia‐inducible factor 1alpha. J Clin Invest 103: 691‐696, 1999.
 647.Yuan JX, Aldinger AM, Juhaszova M, Wang J, Conte JV Jr, Gaine SP, Orens JB, Rubin LJ. Dysfunctional voltage‐gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension. Circulation 98: 1400‐1406, 1998.
 648.Yuan SM. Pulmonary artery hypertension in childhood: The transforming growth factor‐beta superfamily‐related genes. Pediatr Neonatol 59: 112‐119, 2018.
 649.Yun TJ, Coles JG, Konstantinov IE, Al‐Radi OO, Wald RM, Guerra V, de Oliveira NC, Van Arsdell GS, Williams WG, Smallhorn J, Caldarone CA. Conventional and sutureless techniques for management of the pulmonary veins: Evolution of indications from postrepair pulmonary vein stenosis to primary pulmonary vein anomalies. J Thorac Cardiovasc Surg 129: 167‐174, 2005.
 650.Yung D, Widlitz AC, Rosenzweig EB, Kerstein D, Maislin G, Barst RJ. Outcomes in children with idiopathic pulmonary arterial hypertension. Circulation 110: 660‐665, 2004.
 651.Zaidi SH, You XM, Ciura S, Husain M, Rabinovitch M. Overexpression of the serine elastase inhibitor elafin protects transgenic mice from hypoxic pulmonary hypertension. Circulation 105: 516‐521, 2002.
 652.Zamanian RT, Hedlin H, Greuenwald P, Wilson DM, Segal JI, Jorden M, Kudelko K, Liu J, Hsi A, Rupp A, Sweatt AJ, Tuder R, Berry GJ, Rabinovitch M, Doyle RL, de Jesus Perez V, Kawut SM. Features and outcomes of methamphetamine‐associated pulmonary arterial hypertension. Am J Respir Crit Care Med 197: 788‐800, 2018.
 653.Zhang D, Wang G, Han D, Zhang Y, Xu J, Lu J, Li S, Xie X, Liu L, Dong L, Li M. Activation of PPAR‐gamma ameliorates pulmonary arterial hypertension via inducing heme oxygenase‐1 and p21(WAF1): An in vivo study in rats. Life Sci 98: 39‐43, 2014.
 654.Zhang X, Zhang X, Wang S, Luo J, Zhao Z, Zheng C, Shen J. Effects of fasudil on patients with pulmonary hypertension associated with left ventricular heart failure with preserved ejection fraction: A prospective intervention study. Can Respir J 2018: 3148259, 2018.
 655.Zhao Y, Biswas SK, McNulty PH, Kozak M, Jun JY, Segar L. PDGF‐induced vascular smooth muscle cell proliferation is associated with dysregulation of insulin receptor substrates. Am J Physiol Cell Physiol 300: C1375‐C1385, 2011.
 656.Zhao YD, Courtman DW, Deng Y, Kugathasan L, Zhang Q, Stewart DJ. Rescue of monocrotaline‐induced pulmonary arterial hypertension using bone marrow‐derived endothelial‐like progenitor cells: Efficacy of combined cell and eNOS gene therapy in established disease. Circ Res 96: 442‐450, 2005.
 657.Zhou G, Chen T, Raj JU. MicroRNAs in pulmonary arterial hypertension. Am J Respir Cell Mol Biol 52: 139‐151, 2015.
 658.Zhu JH, Wang XX, Zhang FR, Shang YP, Tao QM, Zhu JH, Chen JZ. Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: Open‐label pilot study. Pediatr Transplant 12: 650‐655, 2008.
 659.Zhu N, Gonzaga‐Jauregui C, Welch CL, Ma L, Qi H, King AK, Krishnan U, Rosenzweig EB, Ivy DD, Austin ED, Hamid R, Nichols WC, Pauciulo MW, Lutz KA, Sawle A, Reid JG, Overton JD, Baras A, Dewey F, Shen Y, Chung WK. Exome sequencing in children with pulmonary arterial hypertension demonstrates differences compared with adults. Circ Genom Precis Med 11: e001887, 2018.
 660.Zijlstra WMH, Douwes JM, Rosenzweig EB, Schokker S, Krishnan U, Roofthooft MTR, Miller‐Reed K, Hillege HL, Ivy DD, Berger RMF. Survival differences in pediatric pulmonary arterial hypertension: Clues to a better understanding of outcome and optimal treatment strategies. J Am Coll Cardiol 63: 2159‐2169, 2014.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Pediatric Pulmonary Hypertension: Definitions, Mechanisms, Diagnosis, and Treatment
 

How to Cite

Devashis Mukherjee, Girija G. Konduri. Pediatric Pulmonary Hypertension: Definitions, Mechanisms, Diagnosis, and Treatment. Compr Physiol 2021, 11: 2135-2190. doi: 10.1002/cphy.c200023