Phosphodiesterase Inhibitors for Persistent Pulmonary Hypertension of the Newborn: A Review

Pediatric Pulmonology

Volumn 36, Issue 6, 2003, Pages 529-535

  Travadi, J N ^a   Patole, Sanjay K ^a  

^a KING EDWARD MEMORIAL HOSPITAL   (Australia)

Author keywords

Neonates; Nitric oxide; Phosphodiesterase inhibitors; Pulmonary hypertension

Indexed keywords

15 HYDROXY 11ALPHA,9ALPHA EPOXYMETHANOPROSTA 5,13 DIENOIC ACID; CILOSTAMIDE; CYCLIC AMP; CYCLIC GMP; DIPYRIDAMOLE; MILRINONE; N(G) NITROARGININE METHYL ESTER; NITRIC OXIDE; PENTOXIFYLLINE; PHENOTHIAZINE DERIVATIVE; PHOSPHODIESTERASE INHIBITOR; ROFLUMILAST; ROLIPRAM; SILDENAFIL; ZAPRINAST;

ADULT; ANIMAL MODEL; CHILD; CLINICAL TRIAL; DRUG EFFICACY; DRUG SAFETY; ENZYME INHIBITION; HUMAN; LUNG BLOOD VESSEL; MAJOR CLINICAL STUDY; NEWBORN; NEWBORN DISEASE; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVIEW; SIDE EFFECT; TISSUE DISTRIBUTION; TREATMENT OUTCOME;

DIPYRIDAMOLE; ENDOTHELIUM-DEPENDENT RELAXING FACTORS; HUMANS; INFANT, NEWBORN; NITRIC OXIDE; PENTOXIFYLLINE; PERSISTENT FETAL CIRCULATION SYNDROME; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; PIPERAZINES; PURINONES;

EID: 0346328361     PISSN: 87556863     EISSN: None     Source Type: Journal    
DOI: 10.1002/ppul.10389     Document Type: Review

References (104)

1. 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 2000;105:14-20.
2. Lipkin PH, Davidson D, Spivak L, Straube R, Rhines J, Chang CT. Neurodevelopmental and medical outcomes of persistent pulmonary hypertension in term newborns treated with nitric oxide. J Pediatr 2002;140:306-310.
3. Haworth SG. The pathophysiology of persistent pulmonary hypertension of the newborn. Semin Neonatol 1997;2:13-23.
4. Hoeper MM, Galie N, Simonneau G, Rubin LJ. New treatments for pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:1209-1216.
5. Macrae DJ. Drug therapy in persistent pulmonary hypertension of the newborn. Semin Neonatol 1997;2:49-58.
6. Olschewski H, Olschewski A, Rose F, Schermuly R, Schutte H, Weissmann N, Seeger W, Grimminger F. Physiologic basis for the treatment of pulmonary hypertension. J Lab Clin Med 2001;138:287-297.
7. Steinhorn RH, Morin FC III, Fineman JR. Models of persistent pulmonary hypertension of the newborn (PPHN) and the role of cyclic guanosine monophosphate (GMP) in pulmonary vasorelaxation. Semin Perinatol 1997;21:393-408.
8. Olschewski H, Rose F, Grunig E, Ghofrani HA, Walmrath D, Schulz R, Schermuly R, Grimminger F, Seeger W. Cellular pathophysiology and therapy of pulmonary hypertension. J Lab Clin Med 2001;138:367-377.
9. Reeve HL, Weir EK, Archer SL, Cornfield DN. A maturational shift in pulmonary K+ channels, from Ca2+ sensitive to voltage dependent. Am J Physiol 1998;275:1019-1025.
10. Olschewski H, Seeger W, Grimminger F. Physiology and physiopathology of the pulmonary circulation. Internist (Berlin) 1999;40:696-709.
11. Yang X, Sheares KK, Davie N, Upton PD, Taylor GW, Horsley J, Wharton J, Morrell NW. Hypoxic induction of cox-2 regulates proliferation of human pulmonary artery smooth muscle cells. Am J Respir Cell Mol Biol 2002;27:688-696.
12. Jeffery TK, Wanstall JC. Pulmonary vascular remodelling: a target for therapeutic intervention in pulmonary hypertension. Pharmacol Ther 2001;92:1-20.
13. Finer NN, Barrington KJ. Nitric oxide therapy for the newborn infant. Semin Perinatol 2000;24:59-65.
14. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987;327:524-526.
15. Roberts JD, Polaner DM, Lang P, Zapol WM. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:818-819.
16. Kinsella JP, Neish SR, Shaffer E, Abman SH. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:819-820.
17. Finer NN, Barrington KJ. Nitric oxide in respiratory failure in the newborn infant. Semin Perinatol 1997;21:426-440.
18. Gupta A, Rastogi S, Sahni R, Bhutada A, Bateman D, Rastogi D, Smerling A, Wung JT. Inhaled nitric oxide and gentle ventilation in the treatment of pulmonary hypertension of the newborn-a single-center, 5-year experience. J Perinatol 2002;22:435-441.
19. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev 2001;4:CD000399.
20. Goldman AP, Tasker RC, Haworth SG, Sigston PE, Macrae DJ. Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn. Pediatrics 1996;98:706-713.
21. Abman SH, Kinsella JP. Inhaled nitric oxide for persistent pulmonary hypertension of the newborn: the physiology matters! Pediatrics 1995;96:1153-1155.
22. Thebaud B, Petit T, De Lagausie P, Dall'Ava-Santucci J, Mercier JC, Dinh-Xuan AT. Altered guanylyl-cyclase activity in vitro of pulmonary arteries from fetal lambs with congenital diaphragmatic hernia. Am J Respir Cell Mol Biol 2002;27:42-47.
23. Oka M, Ohnishi M, Takahashi H, Soma S, Hasunuma K, Sato K, et al. Altered vasoreactivity in lungs isolated from rats exposed to nitric oxide gas. Am J Physiol 1996;271:419-424.
24. Black SM, Heidersbach RS, McMullan DM, Bekker JM, Johengen MJ, Fineman JR. Inhaled nitric oxide inhibits NOS activity in lambs: potential mechanism for rebound pulmonary hypertension. Am J Physiol 1999;277:1849-1856.
25. Dotsch J, Demirakca S, Zepf K, Hanze J, Parida S, Rascher W. Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro. Intensive Care Med 2000;26:330-335.
26. Sheehy AM, Burson MA, Black SM. Nitric oxide exposure inhibits endothelial NOS activity but not gene expression: a role for superoxide. Am J Physiol 1998;274:833-841.
27. Pearl JM, Nelson DP, Raake JL, Manning PB, Schwartz SM, Koons L, Shanley TP, Wong HR, Duffy JY. Inhaled nitric oxide increases endothelin-1 levels: a potential cause of rebound pulmonary hypertension. Crit Care Med 2002;30:89-93.
28. Wedgwood S, McMullan DM, Bekker JM, Fineman JR, Black SM. Role for endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy. Circ Res 2001;89:357-364.
29. Truog WE, Pallotto E, Clark P, Banks B, Kaftan HA, Ekekezie II, Norberg M, Ballard RA. Interaction of endogenous endothelin-1 and inhaled nitric oxide in term and preterm infants. Clin Sci [Suppl] 2002;103:294-297.
30. Cueto E, Lopez-Herce J, Sanchez A, Carrillo A. Life-threatening effects of discontinuing inhaled nitric oxide in children. Acta Paediatr 1997;86:1337-1339.
31. 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 1999;104:231-236.
32. Christou H, Adatia I, Van Marter LJ, Kane JW, Thompson JE, Stark AR, et al. Effect of inhaled nitric oxide on endothelin-1 and cyclic guanosine 5′-monophosphate plasma concentrations in newborn infants with persistent pulmonary hypertension. J Pediatr 1997;130:603-611.
33. Kinsella JP, Griebel J, Schmidt JM, Abman SH. Use of inhaled nitric oxide during interhospital transport of newborns with hypoxemic respiratory failure. Pediatrics 2002;109:158-161.
34. Tung BJ. The use of nitric oxide therapy in the transport of newborns with persistent pulmonary hypertension. Air Med J 2001;20:10-11.
35. Kinsella JP, Schmidt JM, Griebel J, Abman SH. Inhaled nitric oxide treatment for stabilization and emergency medical transport of critically ill newborns and infants. Pediatrics 1995;95:773-776.
36. Lonnqvist PA. Efficacy and economy of inhaled nitric oxide in neonates accepted for extra-corporeal membrane oxygenation. Acta Physiol Scand 1999;167:175-179.
37. Subhedar NV, Jauhari P, Natarajan R. Cost of inhaled nitric oxide therapy in neonates. Lancet 2002;359:1781-1782.
38. Pierce CM, Peters MJ, Cohen G, Goldma AP, Petros AJ. Cost of nitric oxide is exorbitant. Br Med J [Clin Res] 2002;325:336.
39. Heal CA, Spencer SA. Methaemoglobineaemia with high-dose nitric oxide administration. Acta Paediatr 1995;84:1318-1319.
40. Salguero KL, Cummings JJ. Inhaled nitric oxide and methemoglobin in full-term infants with persistent pulmonary hypertension of the newborn. Pulm Pharmacol Ther 2002;15:1-5.
41. 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. Pediatrics 1998;101:325-334.
42. Nakajima W, Ischida A, Arai H, Takada G. Methaemoglobinaemia after inhalation of nitric oxide in infant with pulmonary hypertension. Lancet 1997;350:1002-1003.
43. Gaston B, Reilly J, Drazen JM, Fackler J, Ramdev P, Arnelle D, Mullins ME, Sugarbaker DJ, Chee C, Singel DJ. Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci USA 1993;90:10957-10961.
44. Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C. Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. Intensive Care Med 1999;25:911-919.
45. Wedgwood S, McMullan DM, Bekker JM, Fineman JR, Black SM. Role for endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy. Circ Res 2001;89:357-364.
46. Ponka A, Virtanen M. Low-level air pollution and hospital admissions for cardiac and cerebrovascular diseases in Helsinki. Am J Public Health 1996;86:1273-1280.
47. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 1990;87:1620-1624.
48. Haddad IY, Ischiropoulos H, Holm BA, Beckman JS, Baker JR, Matalon S. Mechanisms of peroxynitrite-induced injury to pulmonary surfactants. Am J Physiol 1993;265:555-564.
49. Hallman M, Bry K. Nitric oxide and lung surfactant. Semin Perinatol 1996;20:173-185.
50. Hogman M, Frostell C, Amburg H, Hendenstierna G. Bleeding time prolongation and NO inhalation. Lancet 1993;341:1664-1665.
51. Barrington KJ, Finer NN. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev 2001;4:CD000509.
52. Sutherland EW. Studies on the mechanism of hormone action. Science 1972;177:401-408.
53. Mehats C, Andersen CB, Filopanti M, Jin SL, Conti M. Cyclic nucleotide phosphodiesterases and their role in endocrine cell signalling. Trends Endocrinol Metab 2002;13:29-35.
54. Essayan DM. Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 2001;108:671-680.
55. Essayan DM. Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. Biochem Pharmacol 1999;57:965-973.
56. Soderling SH, Bayuga SJ, Beavo JA. Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase. Proc Natl Acad Sci USA 1998;95:8991-8996.
57. Soderling SH, Bayuga SJ, Beavo JA. Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J Biol Chem 1998;273:15553-15558.
58. Soderling SH, Bayuga SJ, Beavo JA. Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A. Proc Natl Acad Sci USA 1999;96:7071-7076.
59. Hetman JM, Robas N, Baxendale R, Fidock M, Phillips SC, Soderling SH, Beavo JA. Cloning and characterization of two splice variants of human phosphodiesterase 11A. Proc Natl Acad Sci USA 2000;97:12891-12895.
60. Venter JC, et al. The sequence of the human genome. Science 2001;291:1304-1351.
61. Beavo JA, Conti M, Heaslip RJ. Multiple cyclic nucleotide phosphodiesterases. Mol Pharmacol 1994;46:399-405.
62. Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM. Use of sildenafil (Viagra) in patients with cardiovascular disease. Technology and Practice Executive Committee. Circulation 1999;99:168-177.
63. Bushnik T, Conti M. Role of multiple cAMP-specific phosphodiesterase variants. Biochem Soc Trans 1996;24:1014-1019.
64. Houslay MD, Milligan G. Tailoring cAMP-signalling responses through isoform multiplicity. Trends Biochem Sci 1997;22:217-224.
65. Persson CG. On the medical history of xanthines and other remedies for asthma: a tribute to H.H. Salter. Thorax 1985;40:881-886.
66. Fink HA, MacDonald R, Rutks IR, Nelson DB, Wilt TJ. Sildenafil for male erectile dysfunction: a systematic review and meta-analysis. Arch Intern Med 2002;162:1349-1360.
67. Moore R, Edwards J, McQuay H. Sildenafil (Viagra) for male erectile dysfunction: a meta-analysis of clinical trial reports. BMC Urol 2002;2:6.
68. Adatia I. Recent advances in pulmonary vascular disease. Curr Opin Pediatr 2002;14:292-297.
69. Hoeper MM, Galie N, Simonneau G, Rubin LJ. New treatments for pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:1209-1216.
70. Rabe KF, Tenor H, Dent G, Schudt C, Nakashima M, Magnussen H. Identification of PDE isozymes in human pulmonary artery and effect of selective PDE inhibitors. Am J Physiol 1994;266:536-543.
71. Foubert L, De Wolf D, Mareels K, Van Belleghem Y, Reyntjens K, Mortier E, Van Nooten G. Intravenous dipyridamole enhances the effects of inhaled nitric oxide and prevents rebound pulmonary hypertension in piglets. Pediatr Res 2002;52:730-736.
72. Dukarm RC, Morin FC III, Russell JA, Steinhorn RH. Pulmonary and systemic effects of the phosphodiesterase inhibitor dipyridamole in newborn lambs with persistent pulmonary hypertension. Pediatr Res 1998;44:831-837.
73. Saidy K, al-Alaiyan S. The use of L-arginine [correction of F-arginine] and phosphodiesterase inhibitor (dipyridamole) to wean from inhaled nitric oxide. Indian J Pediatr 2001;68:175-177.
74. Thebaud B, Saizou C, Farnoux C, Hartman JF, Mercier JC. Dypiridamole, a cGMP phosphodiesterase inhibitor, transiently improves the response to inhaled nitric oxide in two newborns with congenital diaphragmatic hernia. Intensive Care Med 1999;25:300-303.
75. Buysse C, Fonteyne C, Dessy H, De Laet MH, Biarent D. The use of dipyridamole to wean from inhaled nitric oxide in congenital diaphragmatic hernia. J Pediatr Surg 2001;36:1864-1865.
76. Worwag S, Mulla H, Luyt D, Firmin RK. Dipyridamole in the treatment of a neonate with persistent pulmonary hypertension. J R Soc Med 2000;93:77-78.
77. Al-Alaiyan S, al-Omran A, Dyer D. The use of phosphodiesterase inhibitor (dipyridamole) to wean from inhaled nitric oxide. Intensive Care Med 1996;22:1093-1095.
78. Ivy DD, Ziegler JW, Kinsella JP, Wiggins JW, Abman SH. Hemodynamic effects of dipyridamole and inhaled nitric oxide in pediatric patients with pulmonary hypertension. Chest [Suppl] 1998;114:17.
79. Kinsella JP, Torielli F, Ziegler JW, Ivy DD, Abman SH. Dipyridamole augmentation of response to nitric oxide. Lancet 1995;346:647-648.
80. Nagamine J, Hill LL, Pearl RG. Combined therapy with zaprinast and inhaled nitric oxide abolishes hypoxic pulmonary hypertension. Crit Care Med 2000;28:2420-2424.
81. Steinhorn RH, Gordon JB, Tod ML. Site-specific effect of guanosine 3′,5′-cyclic monophosphate phosphodiesterase inhibition in isolated lamb lungs. Crit Care Med 2000;28:490-495.
82. Ichinose F, Adrie C, Hurford WE, Bloch KD, Zapol WM. Selective pulmonary vasodilation induced by aerosolized zaprinast. Anesthesiology 1998;88:410-416.
83. Thusu KG, Morin FC III, Russell JA, Steinhorn RH. The cGMP phosphodiesterase inhibitor zaprinast enhances the effect of nitric oxide. Am J Respir Crit Care Med 1995;152:1605-1610.
84. Ichinose F, Adrie C, Hurford WE, Zapol WM. Prolonged pulmonary vasodilator action of inhaled nitric oxide by zaprinast in awake lambs. J Appl Physiol 1995;78:1288-1295.
85. Lauterbach R. Pentoxifylline treatment of persistent pulmonary hypertension of newborn. Eur J Pediatr 1993;152:460.
86. Weimann J, Ullrich R, Hromi J, Fujino Y, Clark MW, Bloch KD, Zapol WM. Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension. Anesthesiology 2000;92:1702-1712.
87. Shekerdemian LS, Ravn HB, Penny DJ. Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension. Am J Respir Crit Care Med 2002;165:1098-1102.
88. Ichinose F, Erana-Garcia J, Hromi J, Raveh Y, Jones R, Krim L, Clark MW, Winkler JD, Bloch KD, Zapol WM. Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension. Crit Care Med 2001;29:1000-1005.
89. Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology 1999;91:307-310.
90. Mychaskiw G, Sachdev V, Heath BJ. Sildenafil (Viagra) facilitates weaning of inhaled nitric oxide following placement of a biventricular assist device. J Clin Anesth 2001;13:218-220.
91. Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension. Comparison with inhaled nitric oxide. Circulation 2002;105:2398-2403.
92. Watanabe H, Ohashi K, Takeuchi K, Yamashita K, Yokoyama T, Tran QK, Satoh H, Terada H, Ohashi H, Hayashi H. Sildenafil for primary and secondary pulmonary hypertension. Clin Pharmacol Ther 2002;71:398-402.
93. Ghofrani HA, Wiedemann R, Rose F, Olschewski H, Schermuly RT, Weissmann N, Seeger W, Grimminger F. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 2002;136:515-522.
94. Erickson S, Reyes J, Bohn D, Adatia I. Sildenafil (Viagra) in childhood and neonatal pulmonary hypertension. J Am Coll Cardiol [Suppl] 2002;39:402.
95. Kleinsasser A, Loeckinger A, Hoermann C, et al. Sildenafil modulates hemodynamics and pulmonary gas exchange. Am J Respir Crit Care Med 2001;163:339-343.
96. Lodato RF. Viagra for impotence of pulmonary vasodilator therapy? Am J Respir Crit Care Med 2001;163:312-313.
97. Hyland R, Roe EG, Jones BC, Smith DA: Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol 2001;51:239-248.
98. Lim PH, Moorthy P, Benton KG. The clinical safety of Viagra. Ann NY Acad Sci 2002;962:378-388.
99. 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 1998;338:1397-1404.
100. Behn D, Potter MJ. Sildenafil-mediated reduction in retinal function in heterozygous mice lacking the gamma-subunit of phosphodiesterase. Invest Ophthalmol Vis Sci 2001;42:523-527.
101. Lam CF, Sviri S, Ilett KF, van Heerden PV. Inhaled diazeniumdiolates (NONOates) as selective pulmonary vasodilators. Expert Opin Invest Drugs 2002;11:897-909.
102. Gresser U, Gleiter CH. Erectile dysfunction comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil-review of the literature. Eur J Med Res 2002;7:435-446.
103. Corbin JD, Francis SH. Pharmacology of phosphodiesterase-5 inhibitors. Int J Clin Pract 2002;56:453-459.
104. Walsh-Sukys MC. Persistent pulmonary hypertension of the newborn. The black box revisited. Clin Perinatol 1993;20:127-143.