Pharmacotherapy for Pulmonary Hypertension

Pediatric Clinics of North America

Volumn 59, Issue 5, 2012, Pages 1129-1146

  Steinhorn, Robin H ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Endothelin; Nitric oxide; Phosphodiesterase; Prostacyclin; Pulmonary hypertension; Pulmonary vasculature; Vasodilator

Indexed keywords

AMBRISENTAN; BERAPROST; BOSENTAN; CITRULLINE; CYCLIC GMP; ENDOTHELIN; ENDOTHELIN RECEPTOR ANTAGONIST; ILOPROST; MILRINONE; NITRIC OXIDE; PHOSPHODIESTERASE III; PHOSPHODIESTERASE III INHIBITOR; PLACEBO; PROSTACYCLIN; PROSTANOID; SILDENAFIL; SITAXSENTAN; TADALAFIL; TREPROSTINIL; ANTIHYPERTENSIVE AGENT;

ADJUVANT THERAPY; ARTERIAL OXYGEN TENSION; CHILD HEALTH; CLINICAL EFFECTIVENESS; CONTINUOUS INFUSION; DISEASE CLASSIFICATION; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG DOSE; DRUG DOSE ESCALATION; DRUG EFFECT; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENZYME INHIBITION; EVIDENCE BASED MEDICINE; FEVER; HUMAN; LIFESPAN; LIVER TOXICITY; LUNG ARTERY PRESSURE; LUNG BLOOD FLOW; LUNG BLOOD VESSEL; LUNG VASCULAR RESISTANCE; NAUSEA; NONHUMAN; OPTIMAL DRUG DOSE; PATIENT COMPLIANCE; PENIS ERECTION; PROTEIN EXPRESSION; PROTEIN PROCESSING; PULMONARY HYPERTENSION; QUALITY OF LIFE; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; SYSTEMIC DISEASE; THROMBOCYTE AGGREGATION INHIBITION; TREATMENT DURATION; TREATMENT PLANNING; UPPER RESPIRATORY TRACT INFECTION; CHILD; NEWBORN; PERSISTENT PULMONARY HYPERTENSION;

ANTIHYPERTENSIVE AGENTS; CHILD; HUMANS; HYPERTENSION, PULMONARY; INFANT, NEWBORN; PERSISTENT FETAL CIRCULATION SYNDROME;

EID: 84867070620     PISSN: 00313955     EISSN: 15578240     Source Type: Journal    
DOI: 10.1016/j.pcl.2012.07.011     Document Type: Review

References (123)

1. Levin D.L., Rudolph A.M., Heymann M.A., et al. Morphological development of the pulmonary vascular bed in fetal lambs. Circulation 1976, 53:144-151.
2. Cerro M.J., Abman S., Diaz G., et al. A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: report from the PVRI pediatric taskforce, panama 2011. Pulm Circ 2011, 1:286-298.
3. Simonneau G., Galie N., Rubin L.J., et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004, 43:5S-12S.
4. Simonneau G., Robbins I.M., Beghetti M., et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009, 54:S43-S54.
5. Humbert M., McLaughlin V.V. The 4th world symposium on pulmonary hypertension. introduction. J Am Coll Cardiol 2009, 54:S1-S2.
6. Lammers A.E., Adatia I., Cerro M.J., et al. Functional classification of pulmonary hypertension in children: report from the PVRI pediatric taskforce, panama 2011. Pulm Circ 2011, 1:280-285.
7. Slaughter J.L., Pakrashi T., Jones D.E., et al. Echocardiographic detection of pulmonary hypertension in extremely low birth weight infants with bronchopulmonary dysplasia requiring prolonged positive pressure ventilation. J Perinatol 2011, 31:635-640.
8. An H.S., Bae E.J., Kim G.B., et al. Pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. Korean Circ J 2010, 40:131-136.
9. Farquhar M., Fitzgerald D.A. Pulmonary hypertension in chronic neonatal lung disease. Paediatr Respir Rev 2010, 11:149-153.
10. Khemani E., McElhinney D.B., Rhein L., et al. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics 2007, 120:1260-1269.
11. Abman S.H., Ivy D.D. Recent progress in understanding pediatric pulmonary hypertension. Curr Opin Pediatr 2011, 23:298-304.
12. Robbins I.M., Moore T.M., Blaisdell C.J., et al. Improving outcomes for pulmonary vascular disease. Am J Respir Crit Care Med 2012, 185:1015-1020.
13. Walsh-Sukys M.C., Tyson J.E., Wright L.L., et al. Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics 2000, 105:14-20.
14. Tissot C., Ivy D.D., Beghetti M. Medical therapy for pediatric pulmonary arterial hypertension. J Pediatr 2010, 157:528-532.
15. Oishi P., Datar S.A., Fineman J.R. Advances in the management of pediatric pulmonary hypertension. Respir Care 2011, 56:1314-1339. [discussion: 39-40].
16. Gaston B.M., Carver J., Doctor A., et al. S-nitrosylation signaling in cell biology. Mol Interv 2003, 3:253-263.
17. Tiktinsky M.H., Morin F.C. Increasing oxygen tension dilates fetal pulmonary circulation via endothelium-derived relaxing factor. Am J Physiol Heart Circ Physiol 1993, 265:H376-H380.
18. Mata-Greenwood E., Jenkins C., Farrow K.N., et al. eNOS function is developmentally regulated: uncoupling of eNOS occurs postnatally. Am J Physiol Lung Cell Mol Physiol 2006, 290:L232-L241.
19. Farrow K.N., Lakshminrusimha S., Reda W.J., et al. 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 2008, 295:L979-L987.
20. Kinsella J.P., Parker T.A., Ivy D.D., et al. Noninvasive delivery of inhaled nitric oxide therapy for late pulmonary hypertension in newborn infants with congenital diaphragmatic hernia. J Pediatr 2003, 142:397-401.
21. Konduri G.G., Solimani A., Sokol G.M., et al. A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure. Pediatrics 2004, 113:559-564.
22. Konduri G.G., Vohr B., Robertson C., et al. Early inhaled nitric oxide therapy for term and near-term newborn infants with hypoxic respiratory failure: neurodevelopmental follow-up. J Pediatr 2007, 150:235-240. 40.e1.
23. Gonzalez A., Fabres J., D'Apremont I., et al. 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 2010, 30:420-424.
24. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med 1997, 336:597-604. Neonatal Inhaled Nitric Oxide Study Group.
25. Davidson D., Barefield E.S., Kattwinkel J., et al. Safety of withdrawing inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn. Pediatrics 1999, 104:231-236.
26. Black S.M., Heidersbach R.S., McMullan D.M., et al. Inhaled nitric oxide inhibits NOS activity in lambs: potential mechanism for rebound pulmonary hypertension. Am J Physiol Heart Circ Physiol 1999, 277:H1849-H1856.
27. Thelitz S., Oishi P., Sanchez L.S., et al. Phosphodiesterase-3 inhibition prevents the increase in pulmonary vascular resistance following inhaled nitric oxide withdrawal in lambs. Pediatr Crit Care Med 2004, 5:234-239.
28. Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. Pediatrics 1997, 99:838-845. Neonatal Inhaled Nitric Oxide Study Group.
29. Fliman P.J., deRegnier R.A., Kinsella J.P., et al. Neonatal extracorporeal life support: impact of new therapies on survival. J Pediatr 2006, 148:595-599.
30. Afshar S., Gibson L.L., Yuhanna I.S., et al. Pulmonary NO synthase expression is attenuated in a fetal baboon model of chronic lung disease. Am J Physiol Lung Cell Mol Physiol 2003, 284:L749-L758.
31. Mourani P.M., Ivy D.D., Gao D., et al. Pulmonary vascular effects of inhaled nitric oxide and oxygen tension in bronchopulmonary dysplasia. Am J Respir Crit Care Med 2004, 170:1006-1013.
32. Donohue P.K., Gilmore M.M., Cristofalo E., et al. Inhaled nitric oxide in preterm infants: a systematic review. Pediatrics 2011, 127:e414-e422.
33. Steinhorn R.H., Shaul P.W., deRegnier R.A., et al. Inhaled nitric oxide and bronchopulmonary dysplasia. Pediatrics 2011, 128:e255-e256. [author reply: e6-7].
34. Ballard R.A., Truog W.E., Cnaan A., et al. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med 2006, 355:343-353.
35. Hibbs A.M., Walsh M.C., Martin R.J., et al. One-year respiratory outcomes of preterm infants enrolled in the nitric oxide (to prevent) chronic lung disease trial. J Pediatr 2008, 153:525-529.
36. Barr F.E., Macrae D. Inhaled nitric oxide and related therapies. Pediatr Crit Care Med 2010, 11:S30-S36.
37. Miller O.I., Tang S.F., Keech A., et al. Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study. Lancet 2000, 356:1464-1469.
38. Atz A.M., Adatia I., Lock J.E., et al. Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator testing. J Am Coll Cardiol 1999, 33:813-819.
39. Rossaint R., Falke K.J., Lopez F., et al. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med 1993, 328:399-405.
40. Dobyns E.L., Cornfield D.N., Anas N.G., et al. Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure. J Pediatr 1999, 134:406-412.
41. Sokol J., Jacobs S.E., Bohn D. Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults. Cochrane Database Syst Rev 2003, (1). CD002787.
42. Coggins M.P., Bloch K.D. Nitric oxide in the pulmonary vasculature. Arterioscler Thromb Vasc Biol 2007, 27:1877-1885.
43. Pearson D.L., Dawling S., Walsh W.F., et al. Neonatal pulmonary hypertension-urea-cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function. N Engl J Med 2001, 344:1832-1838.
44. Ananthakrishnan M., Barr F.E., Summar M.L., et al. L-citrulline ameliorates chronic hypoxia-induced pulmonary hypertension in newborn piglets. Am J Physiol Lung Cell Mol Physiol 2009, 297:L506-L511.
45. Smith H.A., Canter J.A., Christian K.G., et al. Nitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrulline. J Thorac Cardiovasc Surg 2006, 132:56-65.
46. Barr F.E., Tirona R.G., Taylor M.B., et al. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg 2007, 134:319-326.
47. Farrow K.N., Steinhorn R.H. Phosphodiesterases: emerging therapeutic targets for neonatal pulmonary hypertension. Handb Exp Pharmacol 2011, 204:251-277.
48. Farrow K.N., Lakshminrusimha S., Czech L., et al. Superoxide dismutase and inhaled nitric oxide normalize phosphodiesterase 5 expression and activity in neonatal lambs with persistent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2010, 299:L109-L116.
49. Sanchez L.S., Filippov G., Zapol W.M., et al. cGMP-binding, cGMP-specific phosphodiesterase gene expression is regulated during lung development. Pediatr Res 1995, 37:348A.
50. Hanson K.A., Abman S.H., Clarke W.R. Elevation of pulmonary PDE5-specific activity in an experimental fetal ovine perinatal pulmonary hypertension model. Pediatr Res 1996, 39:334A.
51. Farrow K.N., Wedgwood S., Lee K.J., et al. Mitochondrial oxidant stress increases PDE5 activity in persistent pulmonary hypertension of the newborn. Respir Physiolo Neurobiol 2010, 174:272-281.
52. Nagendran J., Archer S.L., Soliman D., et al. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation 2007, 116:238-248.
53. Atz A.M., Wessel D.L. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology 1999, 91:307-310.
54. Lee J.E., Hillier S.C., Knoderer C.A. Use of sildenafil to facilitate weaning from inhaled nitric oxide in children with pulmonary hypertension following surgery for congenital heart disease. J Intensive Care Med 2008, 23:329-334.
55. Namachivayam P., Theilen U., Butt W.W., et al. Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. Am J Respir Crit Care Med 2006, 174:1042-1047.
56. Barst R.J., Ivy D.D., Gaitan G., et al. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation 2012, 125:324-334.
57. Baquero H., Soliz A., Neira F., et al. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics 2006, 117:1077-1083.
58. Fraisse A., Butrous G., Taylor M.B., et al. Intravenous sildenafil for postoperative pulmonary hypertension in children with congenital heart disease. Intensive Care Med 2011, 37:502-509.
59. Steinhorn R.H., Kinsella J.P., Pierce C., et al. Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension. J Pediatr 2009, 155:841-847.
60. Ladha F., Bonnet S., Eaton F., et al. Sildenafil improves alveolar growth and pulmonary hypertension in hyperoxia-induced lung injury. Am J Respir Crit Care Med 2005, 172:750-756.
61. Mourani P.M., Sontag M.K., Ivy D.D., et al. Effects of long-term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease. J Pediatr 2009, 154:379-384. 84 e1-2.
62. Keller R.L., Moore P., Teitel D., et al. Abnormal vascular tone in infants and children with lung hypoplasia: findings from cardiac catheterization and the response to chronic therapy. Pediatr Crit Care Med 2006, 7:589-594.
63. Luong C., Rey-Perra J., Vadivel A., et al. Antenatal sildenafil treatment attenuates pulmonary hypertension in experimental congenital diaphragmatic hernia. Circulation 2011, 123:2120-2131.
64. Takatsuki S., Calderbank M., Ivy D.D. Initial experience with tadalafil in pediatric pulmonary arterial hypertension. Pediatr Cardiol 2012, 33(5):683-688.
65. Brannon T.S., MacRitchie A.N., Jaramillo M.A., et al. Ontogeny of cyclooxygenase-1 and cyclooxygenase-2 gene expression in ovine lung. Am J Phys 1998, 274:L66-L71.
66. Brannon T.S., North A.J., Wells L.B., et al. Prostacyclin synthesis in ovine pulmonary artery is developmentally regulated by changes in cyclooxygenase-1 gene expression. J Clin Invest 1994, 93:2230-2235.
67. Christman B.W., McPherson C.D., Newman J.H., et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 1992, 327:70-75.
68. Lakshminrusimha S., Porta N.F., Farrow K.N., et al. Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn. Pediatr Crit Care Med 2009, 10:106-112.
69. Jones R.L., Qian Y., Wong H.N., et al. Prostanoid action on the human pulmonary vascular system. Clin Exp Pharmacol Physiol 1997, 24:969-972.
70. Rosenzweig E.B., Kerstein D., Barst R.J. Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation 1999, 99:1858-1865.
71. Barst R.J., Maislin G., Fishman A.P. Vasodilator therapy for primary pulmonary hypertension in children. Circulation 1999, 99:1197-1208.
72. Barst R.J., Rubin L.J., Long W.A., et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. the primary pulmonary hypertension study group. N Engl J Med 1996, 334:296-302.
73. Barst R.J., Rubin L.J., McGoon M.D., et al. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994, 121:409-415.
74. Sitbon O., Humbert M., Nunes H., et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 2002, 40:780-788.
75. Yung D., Widlitz A.C., Rosenzweig E.B., et al. Outcomes in children with idiopathic pulmonary arterial hypertension. Circulation 2004, 110:660-665.
76. D'Alonzo G.E., Barst R.J., Ayres S.M., et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991, 115:343-349.
77. Doran A.K., Ivy D.D., Barst R.J., et al. Guidelines for the prevention of central venous catheter-related blood stream infections with prostanoid therapy for pulmonary arterial hypertension. Int J Clin Pract Suppl 2008, 160:5-9.
78. Zwissler B., Rank N., Jaenicke U., et al. Selective pulmonary vasodilation by inhaled prostacyclin in a newborn with congenital heart disease and cardiopulmonary bypass. Anesthesiology 1995, 82:1512-1516.
79. Bindl L., Fahnenstich H., Peukert U. Aerosolised prostacyclin for pulmonary hypertension in neonates. Arch Dis Child Fetal Neonatal Ed 1994, 71:F214-F216.
80. Soditt V., Aring C., Groneck P. Improvement of oxygenation induced by aerosolized prostacyclin in a preterm infant with persistent pulmonary hypertension of the newborn. Intensive Care Med 1997, 23:1275-1278.
81. Olmsted K., Oluola O., Parthiban A., et al. Can inhaled prostacyclin stimulate surfactant in ELBW infants?. J Perinatol 2007, 27:724-726.
82. Kelly L.K., Porta N.F., Goodman D.M., et al. Inhaled prostacyclin for term infants with persistent pulmonary hypertension refractory to inhaled nitric oxide. J Pediatr 2002, 141:830-832.
83. Kumar V.H., Swartz D.D., Rashid N., et al. Prostacyclin and milrinone by aerosolization improve pulmonary hemodynamics in newborn lambs with experimental pulmonary hypertension. J Appl Phys 2010, 109:677-684.
84. Porta N.F., Steinhorn R.H. Pulmonary vasodilator therapy in the NICU: inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents. Clin Perinatol 2012, 39:149-164.
85. Ewert R., Schaper C., Halank M., et al. Inhalative iloprost-pharmacology and clinical application. Expert Opin Pharmacother 2009, 10:2195-2207.
86. Ehlen M., Wiebe B. Iloprost in persistent pulmonary hypertension of the newborn. Cardiol Young 2003, 13:361-363.
87. Eifinger F., Sreeram N., Mehler K., et al. Aerosolized iloprost in the treatment of pulmonary hypertension in extremely preterm infants: a pilot study. Klin Padiatr 2008, 220:66-69.
88. Hallioglu O., Dilber E., Celiker A. Comparison of acute hemodynamic effects of aerosolized and intravenous iloprost in secondary pulmonary hypertension in children with congenital heart disease. Am J Cardiol 2003, 92:1007-1009.
89. Ivy D.D., Doran A.K., Smith K.J., et al. Short- and long-term effects of inhaled iloprost therapy in children with pulmonary arterial hypertension. J Am Coll Cardiol 2008, 51:161-169.
90. Limsuwan A., Wanitkul S., Khosithset A., et al. Aerosolized iloprost for postoperative pulmonary hypertensive crisis in children with congenital heart disease. Int J Cardiol 2008, 129:333-338.
91. Muller M., Scholz S., Kwapisz M., et al. Use of inhaled iloprost in a case of pulmonary hypertension during pediatric congenital heart surgery. Anesthesiology 2003, 99:743-744.
92. Tissot C., Beghetti M. Review of inhaled iloprost for the control of pulmonary artery hypertension in children. Vasc Health Risk Manag 2009, 5:325-331.
93. De Luca D., Zecca E., Piastra M., et al. Iloprost as 'rescue' therapy for pulmonary hypertension of the neonate. Paediatr Anaesth 2007, 17:394-395.
94. Chotigeat U., Jaratwashirakul S. Inhaled iloprost for severe persistent pulmonary hypertension of the newborn. J Med Assoc Thai 2007, 90:167-170.
95. Ivy D.D., Claussen L., Doran A. Transition of stable pediatric patients with pulmonary arterial hypertension from intravenous epoprostenol to intravenous treprostinil. Am J Cardiol 2007, 99:696-698.
96. Levy M., Celermajer D.S., Bourges-Petit E., et al. Add-on therapy with subcutaneous treprostinil for refractory pediatric pulmonary hypertension. J Pediatr 2011, 158:584-588.
97. Simonneau G., Barst R.J., Galie N., et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary hypertension. Am J Respir Crit Care Med 2002, 165:1-5.
98. Chen B., Lakshminrusimha S., Czech L., et al. Regulation of phosphodiesterase 3 in the pulmonary arteries during the perinatal period in sheep. Pediatr Res 2009, 66:682-687.
99. Hoffman T.M., Wernovsky G., Atz A.M., et al. Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation 2003, 107:996-1002.
100. Chang A.C., Atz A.M., Wernovsky G., et al. Milrinone: systemic and pulmonary effects in neonates after cardiac surgery. Crit Care Med 1995, 23:1907-1914.
101. Bassler D., Choong K., McNamara P., et al. Neonatal persistent pulmonary hypertension treated with milrinone: four case reports. Biol Neonate 2006, 89:1-5.
102. Deb B., Bradford K., Pearl R.G. Additive effects of inhaled nitric oxide and intravenous milrinone in experimental pulmonary hypertension. Crit Care Med 2000, 28:795-799.
103. McNamara P.J., Laique F., Muang-In S., et al. Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn. J Crit Care 2006, 21:217-222.
104. Abman S.H. Role of endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. Annu Rev Med 2009, 60:13-23.
105. Giaid A., Yanagisawa M., Lagleben D., et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993, 328:1732-1739.
106. Hiramatsu T., Imai Y., Takanashi Y., et al. Time course of endothelin-1 and nitrate anion levels after cardiopulmonary bypass in congenital heart defects. Ann Thorac Surg 1997, 63:648-652.
107. Komai H., Adatia I.T., Elliott M.J., et al. Increased plasma levels of endothelin-1 after cardiopulmonary bypass in patients with pulmonary hypertension and congenital heart disease. J Thorac Cardiovasc Surg 1993, 106:473-478.
108. Reddy M.V., Hendricks-Munoz K.D., Rajasinghe H.A., et al. Post-cardiopulmonary bypass pulmonary hypertension in lambs with increased pulmonary blood flow: a role for endothelin 1. Circulation 1997, 95:1054-1061.
109. Schulze-Neick I., Li J., Reader J.A., et al. The endothelin antagonist BQ123 reduces pulmonary vascular resistance after surgical intervention for congenital heart disease. J Thorac Cardiovasc Surg 2002, 124:435-441.
110. Keller R.L., Tacy T.A., Hendricks-Munoz K., et al. Congenital diaphragmatic hernia: endothelin-1, pulmonary hypertension, and disease severity. Am J Respir Crit Care Med 2010, 182:555-561.
111. Rubin L.J., Badesch D.B., Barst R.J., et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002, 346:896-903.
112. Channick R.N., Simonneau G., Sitbon O., et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 2001, 358:1119-1123.
113. Rosenzweig E.B., Ivy D.D., Widlitz A., et al. Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol 2005, 46:697-704.
114. Maiya S., Hislop A.A., Flynn Y., et al. Response to bosentan in children with pulmonary hypertension. Heart 2006, 92:664-670.
115. Barst R.J., Ivy D., Dingemanse J., et al. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin Pharmacol Ther 2003, 73:372-382.
116. Nakwan N., Choksuchat D., Saksawad R., et al. Successful treatment of persistent pulmonary hypertension of the newborn with bosentan. Acta Paediatr 2009, 98:1683-1685.
117. Goissen C., Ghyselen L., Tourneux P., et al. Persistent pulmonary hypertension of the newborn with transposition of the great arteries: successful treatment with bosentan. Eur J Pediatr 2008, 167:437-440.
118. Ivy D.D., Doran A., Claussen L., et al. Weaning and discontinuation of epoprostenol in children with idiopathic pulmonary arterial hypertension receiving concomitant bosentan. Am J Cardiol 2004, 93:943-946.
119. van Loon R.L., Hoendermis E.S., Duffels M.G., et al. Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt: does the beneficial effect persist?. Am Heart J 2007, 154:776-782.
120. Beghetti M., Hoeper M.M., Kiely D.G., et al. Safety experience with bosentan in 146 children 2-11 years old with pulmonary arterial hypertension: results from the European Postmarketing Surveillance program. Pediatr Res 2008, 64:200-204.
121. Channick R.N., Sitbon O., Barst R.J., et al. Endothelin receptor antagonists in pulmonary arterial hypertension. J Am Coll Cardiol 2004, 43:62S-67S.
122. Galie N., Badesch D., Oudiz R., et al. Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2005, 46:529-535.
123. Galie N., Olschewski H., Oudiz R.J., et al. 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 2008, 117:3010-3019.