Advances in the medical treatment of pulmonary hypertension

Kidney and Blood Pressure Research

Volumn 28, Issue 5-6, 2006, Pages 311-324

  Dandel, Michael ^a   Lehmkuhl, Hans B ^a   Hetzer, Roland ^a  

^a DEUTSCHES HERZZENTRUM BERLIN   (Germany)

Author keywords

Endothelin; Nitric oxide; Phosphodiesterase inhibitors; Prostacyclin; Pulmonary hypertension

Indexed keywords

ADENOSINE; ADRENOMEDULLIN; AMBRISENTAN; AMINOTRANSFERASE; ANTIHYPERTENSIVE AGENT; ARGININE; BERAPROST; BOSENTAN; DARUSENTAN; ELASTASE INHIBITOR; ENDOTHELIN 1; ENDOTHELIN RECEPTOR ANTAGONIST; ILOPROST; NITRIC OXIDE; PHOSPHODIESTERASE III INHIBITOR; PHOSPHODIESTERASE INHIBITOR; PHOSPHODIESTERASE IV INHIBITOR; PHOSPHODIESTERASE V INHIBITOR; POTASSIUM CHANNEL STIMULATING AGENT; PROSTACYCLIN; PROSTACYCLIN DERIVATIVE; SEROTONIN ANTAGONIST; SILDENAFIL; SITAXSENTAN; THROMBOXANE RECEPTOR BLOCKING AGENT; THROMBOXANE SYNTHASE INHIBITOR; TOLAFENTRINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; UNIPROST; WARFARIN;

ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; CHRONIC KIDNEY FAILURE; CLINICAL TRIAL; DIARRHEA; DISEASE CLASSIFICATION; DRUG INDUCED HEADACHE; FOOT PAIN; GENE THERAPY; HEMODIALYSIS; HOT FLUSH; HUMAN; INDIGESTION; INJECTION SITE ERYTHEMA; INJECTION SITE PAIN; LIFE EXPECTANCY; LIVER DISEASE; LIVER DYSFUNCTION; LIVER TOXICITY; LUNG VASCULAR RESISTANCE; NAUSEA; NONHUMAN; PRIORITY JOURNAL; PULMONARY HYPERTENSION; QUALITY OF LIFE; RETINA INJURY; THROMBOCYTOPENIA; WEIGHT REDUCTION;

ANTIHYPERTENSIVE AGENTS; ARGININE; EPOPROSTENOL; HUMANS; HYPERTENSION, PULMONARY; NITRIC OXIDE; PHOSPHODIESTERASE INHIBITORS; RECEPTORS, ENDOTHELIN; TERMINOLOGY;

EID: 33644983373     PISSN: 14204096     EISSN: None     Source Type: Journal    
DOI: 10.1159/000090186     Document Type: Article

References (140)

1. 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 1992;327:76-81.
2. Hoeper MM, Wilke T, Welte T, Breuer HWM Wagner TOF: How effective is the treatment with high-dose nifedipine for primary pulmonary hypertension. Semin Respir Crit Care Med 1994;15:490-494.
3. Fishmann AP: Pulmonary Hypertension; in Wayne AR, Schlant RC, Fuster V (eds): Hurst's The Heart. New York, McGraw-Hill, 1998, pp 1699-1717.
4. Rich S, Rubin LJ, Abenhaim MD, et al: Primary Pulmonary Hypertension. Executive Summary from the World Symposium-Primary Pulmonary Hypertension 1998 Evian, France, September 6-10; in Rich S (ed): WHO document 1998, pp 1-27.
5. Simonneau G, Nazzareno G, Rubin LJ, et al: Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004;43/12(suppl):5S-12S.
6. Tuder R, Cool C, Geraci M, et al: Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 1999;159:1925-1932.
7. Chen YF, Oparil S: Endothelial dysfunction in the pulmonary vascular bed. Am J Med Sci 2000;320:223-232.
8. Giaid A, Saleh D: Reduced expression of endothelial nitric oxide synthetase in the lungs of patients with pulmonary hypertension N Engl J Med 1995;333:214-221.
9. Giaid A, Yanagisawa M, Langleben D, et al: Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993;328:1732-1739.
10. Tilton RG, Brock TA, Dixon RAF: Therapeutic potential of endothelin receptor antagonists and nitric oxide donors in pulmonary hypertension. Expert Opin Invest Drugs 2001;10:1291-1308.
11. McLaughlin V: Medical management of primary pulmonary hypertension. Expert Opin Pharmacother 2002;3:159-165.
12. Tuder RM, Cool CD, Yeager M, et al: The pathobiology of pulmonary hypertension: endothelium. Clin Chest Med 2001;22:405-418.
13. Tuder RM, Zaiman AL: Prostacyclin analogs as the brakes for pulmonary artery smoth muscle cell proliferation. Am J Respir Cell Mol Biol 2002;26:171-174.
14. Tuder RM, Chacon M, Alger L, et al: Expression of angiogenesis related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis. J Pathol 2001;195:367-374.
15. Cool CD, Rai PR, Yeager ME, et al: Expression of human herpesvirus 8 in primary pulmonary hypertension. N Engl J Med 2003;349:1107-1109.
16. Christman B, McPherson C, Newmann J, et al: An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 1992;327:70-75.
17. De Backer LM, Smedema J-P, Carlier SG: Current management of primary pulmonary hypertension. Biodrugs 2001;15:801-817.
18. McLaughlin V, Shillington A, Rich S: Survival in primary pulmonary hypertension. The impact of epoprostenol therapy. Circulation 2002;106:1477-1482.
19. Riley MS, Porszasz J, Engelen MP, Shapiro SM, Brangage BH, Wassermann K: Responses to constant work rate bicycle ergometry exercise in primary pulmonary hypertension: the effect of inhaled nitric oxide. J Am Coll Cardiol 2000;36:547-556.
20. Krasuski RA, Warner JJ, Wang A, Shapiro SM, Brandage BH, Wassermann K: Inhaled nitric oxide selectively dilates pulmonary vasculature in adult patients with pulmonary hypertension, irrespective of etiology. J Am Coll Cardiol 2000;36:2204-2211.
21. Abrams D, Schulze-Neick I, Magee AG: Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Heart 2000;84:E4.
22. Prasad S, Wilkinson J, Gatzoulis MA: Sildenafil in primary pulmonary hypertension. N Engl J Med 2000;343:1342.
23. Tuder RM, Groves B, Badesch DB, Voelkel MF: Exuberant endothelial cell growth and elements in inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 1994;144:275-285.
24. Tuder R: Plexiform lesions in primary pulmonary hypertension may represent an abnormal form of angiogenesis. Crit Care Med 1994;15:207-214.
25. Yi ES, Kim H, Ahn H, Strother J, et al: Distribution of obstructive intimai lesions and their cellular phenotype in chronic pulmonary hypertension. Am J Respir Crit Care Med 2000;162:1577-1586.
26. Hoeper MM, Galie N, Simonneau G, Rubin LJ: New treatments of pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:1209-1216.
27. Naruiya S, Sugimoto Y, Ushikubi F: Prostanoid receptors: structures, properties and function. Physiol Rev 1999;79:1193-1226.
28. Rich S, McLaughlin V: The effects of chronic prostacyclin on cardiac output and symptoms in primary pulmonary hypertension. J Am Coll Cardiol 1999;34:1184-1187.
29. D'Acquisito F, Sautebin L, Iuvone T, Di Rosa M, Carnuccio R: Prostaglandins prevent inducible nitric oxide synthetase protein expression by inhibiting nuclear factor-kB activation in J774 macrophages. FEBS Lett 1998;440:76-80.
30. Rubin L, Mendoza J, Hood M, et al: Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Ann Intern Med 1990;112:485-491.
31. Barst R, Rubin L, McGoon M, Caldwell EJ, Long WA, Levy PS: Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994;121:409-415.
32. Barst R, Rubin L, Long W, et al: A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996;334:296-301.
33. McLaughlin V, Genthner D, Panella MM, Rich S: Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 1998;338:273-277.
34. Shapiro S, Ouditz R, Cao T, et al: Primary pulmonary hypertension: improved long-term effects and survival with continuous intravenous epoprostenol infusion. J Am Coll Cardiol 1997;30:343-349.
35. McLaughlin V, Genthner D, Panella M, Hess DM, Rich S: Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension: a case series. Ann Intern Med 1999;190:130:740-743.
36. Badesch DB, Tapson VP, McGoon MD, et al: Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. Ann Intern Med 2000;132:425-432.
37. Humbert M, Sanchez O, Fartoukh M, et al: Short-term and long-term epoprostenol (prostacyclin therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study. Eur Respir J 1999;13:1351-1356.
38. Hoeper MM: Pulmonary hypertension in collagen vascular disease. Eur Respir J 2002;19:571-576.
39. Krowka MJ, Frantz RP, McGoon MD, et al: Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): a study of 15 patients with moderate to severe portopulmonary hypertension. Hepatology 1999;30:641-648.
40. Rosenzweig E, Kerstein D, Barst R: Long-term prostacyclin for pulmonary hypertension with associated congenital defects. Circulation 1999;99:1858-1865.
41. Robbins IM, Gaine SP, Schilz P, et al: Epoprostenol for treatment of pulmonary hypertension in patients with systemic lupus erythematosus Chest 2000;117:14-18.
42. Aguilar RV, Farber HW: Epoprostenol (prostacyclin9 therapy in HIV-associated pulmonary hypertension. Am J Respir Crit Care Med 2000;162:1846-1850.
43. Kuo PC, Johnson LB, Plotkin JS, et al: Continuous intravenous infusions of epoprostenol for the treatment of portopulmonary hypertension. Transplantation 1997;63:604-606.
44. Clapp LH, Finney P, Turcato S, et al: Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human artery. Am J Resp Cell Mol Biol 2002;26:194-201.
45. Striker H, Domenighetti G, Fiori G Mombelli G: Sustained improvement of performance and haemodynamics with long-term aerosolized prostacyclin therapy in severe pulmonary hypertension. Schweiz Med Wochenschr 1999;129:923-927.
46. Parameswaran K, Purcell I, Farrer M, Holland C, Taylor IK, Keany NP: Acute effects of nebulised epoprostenol in pulmonary hypertension due to systemic sclerosis. Respir Med 1999;93:75-78.
47. Olschewski H, Ghofrani HA, Schmehl T, et al: Inhaled iloprost to treat severe pulmonary hypertension: an uncontrolled trial. Ann Intern Med 2000;132:435-443.
48. Galie N, Manus A, Branzi A: Prostanoids for pulmonary arterial hypertension. Am J Respir Med 2003;2:123-137.
49. Olschewski H, Walmrath D, Schermuly R, et al: Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann Intern Med 1996;124:820-824.
50. Higenbottam TW, Butt AY, Dinh-Xaun AT, et al: Treatment of pulmonary hypertension with continuous infusion of a prostacyclin analog, iloprost. Heart 1998;79:175-179.
51. Hoeper MM, Schwarze M, Ehlerding S, et al: Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analog. N Engl J Med 2000;342:1866-1870.
52. Hoeper MM, Olschewski HA, Ghofrani HA, et al: A comparison of the acute nemo-dynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. J Am Coll Cardiol 2000;35:176-182.
53. Olschewski HA, Simonneau G, Galie N, et al: Inhaled Iloprost for severe pulmonary hypertension. N Engl J Med 2002;347:322-329.
54. Grant SM, Goa KL: Iloprost: a review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic potential in peripheral vascular disease, myocardial ischemia and extracorporeal circulation procedures. Drugs 1992;43:889-924.
55. Olschewski H, Ghofrani HA, Walmrath D, et al: Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am J Respir Crit Care Med 1999;160:600-607.
56. Wensel R, Opitz CF, Ewert R, Bruch L, Kleber FX: Effects of iloprost inhalation on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension. Circulation 2000;101:2388-2392.
57. Machherndl S, Kneussl M, Baumgartner H, et al: Long-term treatment of pulmonary hypertension with aerosolized iloprost. Eur Respir J 2001;17:8-13.
58. Ewert R, Opitz C, Wensel R, et al: Iloprost as inhalative or intravenous long-term treatment of patients with primary pulmonary hypertension. Z Kardiol 2000;89:987-999.
59. Melian EB, Goa KL: Beraprost: a review of its pharmacological and therapeutic efficacy in the treatment of peripheral arterial disease and pulmonary arterial hypertension. Drugs 2002;62:107-133.
60. Ichida F, Uese K, Hamamichi Y, et al: Chronic effects of oral prostacyclin analogue on thromboxane A2 and prostacyclin metabolites in pulmonary hypertension. Acta Paediatr Jpn 1998;40:14-19.
61. Saji T, Ozawa Y, Nakayama T, et al: Short- and long-term effects of the new oral prostacyclin analogue, beraprost sodium, in patients with severe pulmonary hypertension. J Cardiol 1996;27:197-205.
62. Vizza CD, Sciomer S, Morelli S, et al: Long term treatment of pulmonary arterial hypertension with beraprost, an oral prostacyclin analogue. Heart 2001;86:603-604.
63. Nagaya N, Shimizu Y, Satoh T, et al: Oral beraprost sodium improves exercise capacity and ventilatory efficiency an patients with primary or thomboembolic pulmonary hypertension. Heart 2002;87:340-345.
64. Nagaya N, Uematsu M, Okano Y, et al: Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension. J Am Coll Cardiol 1999;34: 1188-1192.
65. Galie N, Humbert M, Vachiery JL, et al: Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: A randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 2002;39:1496-1502.
66. Barst RJ, McGoon M, McLaughlin V, et al: Beraprost therapy for pulmonary arterial hypertension. Am J Coll Cardiol 2003;41:2119-2125.
67. Abe Y, Tatsumi K, Sugito K, et al: Effects of inhaled prostacyclin analogue on chronic hypoxic pulmonary hypertension. J Cardiovasc Pharmacol 2001;37:239-251.
68. Steffen PP, de la Mata M: The effects of 15AU8I, a chemically stable prostacyclin analog on the cardiovascular and renin-angiotensin Systems of anesthetized dogs. Prostaglandins Leukot Essent Fatty Acids 1991;43:277-286.
69. Hamilton G, Saba T, Corris P, et al: Improvement of exercise tolerance due to uniprost in patients with pulmonary arterial hypertension is related to baseline performance. Am J Respir Crit Care Med 2001;163:A540.
70. Galie N, Manes A, Branzi A: Medical therapy of pulmonary hypertension: the prostacyclins. Clin Chest Med 2001;22:529-537.
71. Fink AN, Frishman WH, Azizad M, Agarwal Y: Use of prostacyclin and its analogues in the treatment of cardiovascular disease. Heart Dis 1999;1:29-40.
72. Chattaraj SC: Treprostinul sodium: pharmacia. Curr Opin Drugs 2002;3:582-586.
73. Horn EM, Barst RJ: Treprostinil therapy for pulmonary artery hypertension. Expert Opin Invest Drugs 2002;11:1615-1622.
74. Simmoneau G, Barst RJ, Galie N, et al: Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind randomized controlled trial. Am J Crit Care Med 2002;165:800-804.
75. Kirchengast M, Luz M: Endothelin receptor antagonists: clinical realities and future directions. J Cardiovasc Pharmacol 2005;45:182-192.
76. Yanagisawa MH, Kurihara H, Kimura S, et al: A novel vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988;332:411-415.
77. Rich SR, McLaughlin W: Endothelin receptor blockers in cardiovascular disease. Circulation 2003;108:2184-2190.
78. Hocher B, Thone-Reineke C, Raschak M, Neumayer HH: The paracrine endothelin system: pathophysiology and implications in clinical medicine. Eur J Clin Chem Clin Biochem 1997;35:175-189.
79. Rakugi H, Tabuchi Y, Nakamaru M, et al: Evidence for endothelin-1 release from resistance vessels of rats in response to hypoxia. Biochem Biophys Res Commun 1990;169:973-977.
80. Cunningham ME, Muribal M, Bala RJ, et al: Endothelin-1 and endothelin-4 stimulate monocyte production of cytokines. Crit Care Med 1997;25:958-964.
81. Zouki C, Baron C, Fournier A, Filep JG: Endothelin-1 enhances neutrophil adhesion to human coronary artery endothelial cells: role of ET(A) receptors and platelet-activating factor. Br J Pharmacol 1999 127:969-979.
82. Park SH, Saleh D, Giad A, Michel RP: Increased endothelin-1 in bleomycin-induced pulmonary fibrosis and the effect on an endothelin receptor antagonist. Am J Resp Crit Care Med 1997;156:600-608.
83. Yoshida K, Yasujima M, Kohzuki M, et al: Endothelin- 1 augments pressor response to angiotensin II infusion in rats. Hypertension 1992; 20:292-297.
84. MacLean MR: Endothelin-1: A mediator of pulmonary hypertension? Pulm Pharmacol Ther 1998;11:125-132.
85. Love MP, Haynes WG, Gray GA, et al: Vasodilator effects of endothelin-converting enzyme inhibition and endothelin ETA receptor blockade in chronic heart failure patients treated with ACE inhibitors. Circulation 1996;94:2131-2137.
86. Nootens M, Kaufmann E, Rector T, et al: Neurohormonal activation in patients with right ventricular failure from pulmonary hypertension: relation to hemodynamic variables and endothelin levels. J Am Coll Cardiol 1995;26:1581-1585.
87. Yamane K, Kasiwagi H, Suzuki N, et al: Elevated plasma levels of endothelin-1 in systemic sclerosis. Arthritis Rheum 1991;34:243-244.
88. Bauer M, Wilkens H, Langer F, et al: Selective upregulation of endothelin B receptor gene expression in severe pulmonary hypertension. Circulation 2002;105:1034-1036.
89. McCulloch KM, Docherty CC, Morecroft I, et al: Endothelin B receptor-mediated contraction in human pulmonary resistance arteries. Br J Pharmacol 1996;119:1125-1130.
90. Chen SJ, Chen YF, Meng QC, et al: Endothelin-receptor antagonist bosentan prevents and reverses hypoxic pulmonary hypertension in rats. J Appl Physiol 1995;79:2122-2131.
91. B receptors. Br J Pharmacol 1995;115:227-236.
92. Williamson DJ, Wallman LL, Jones R, et al: Hemodynamic effects of bosentan, and endothelin receptor antagonist, in patients with pulmonary hypertension. Circulation 2000;102:411-418.
93. Channick RN, Simonneau G, Sitbon O, et al: Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary hypertension: a randomized placebo-controlled study. Lancet 2001;358:1119-1123.
94. Sitbon O, Badesch DB, Cannik RN, et al: Effects of the dual endothelin receptor antagonist bosentgan in patients with pulmonary arterial hypertension: a 1 year follow up. Chest 2003;124:247-254.
95. Rubin LJ, Badesch DB, Barst RJ, et al: Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346:896-903.
96. Kenyon KW, Nappi JM: Bosentan for the treatment of pulmonary arterial hypertension. Ann Pharmacother 2003;37:1055-1062.
97. Murphey LM, Hood EH: Bosentan and warfarin interaction. Ann Pharmacother 2003;37:1028-1031.
98. Barst RJ, Ivi 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.
99. Liefeldt L, van Giersbergen PL, Dingemanse J, et al: Treatment of secondary pulmonary hypertension with bosentan and its pharmacokinetic monitoring in ESRD. Am J Kidney Dis 2004;43:923-926.
100. Yigla M, Nakhoul F, Sabag A, Tov N, Gorevich B, et al: Pulmonary hypertension in patients with end-stage renal disease. Chest 2003;123:1577-1582.
101. Barst RJ, Rich S, Widlitz A, et al: Clinical efficacy of sitaxsentan, an oral endothelin: a receptor antagonist, in patients with pulmonary arterial hypertension. Chest 2002;121:1860-1868.
102. A antagonist improves cardiopulmonary hemodynamics in pulmonary arterial hypertension (PAH). Am J Respir Crit Care Med 2003;167:A273.
103. Schermuly RT, Roehl A, Weissmann R, et al: Subthreshold doses of specific phosphodiesterase type 3 and 4 inhibitors enhance the pulmonary vasodilatory response to nebulized prostacyclin with improvement in gas exchange. J Pharmacol Exp Ther 2000;292:512-520.
104. Ichinose F, Erana-Garcia J, Hromi J, et al: Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension. Crit Care Med 2001;29:1000-1005.
105. Kleinsasser A, Loeckinger A, Hoermann C, et al: Sildenafil modulates haemodynamics and pulmonary gas exchange. Am J Respir Crit Care Med 2001;163:339-343.
106. Weinmann J, Ulrich R, Hromi J, et al: Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension. Anesthesiology 2000;92:1702-1712.
107. Travadi JN, Patole SK: Phospodiesterase inhibitors for persistent pulmonary hypertension of the newborn: a review. Pediatr Pulmonol 2003;36:529-535.
108. Bhatia S, Frantz RP, Seversen CJ, et al: Immediate and long-term hemodynamic and clinical effects of sildenafil in patients with pulmonary arterial hypertension receiving vasodilator therapy. Mayo Clin Proc 2003;78:1207-1213.
109. Cheitlin MD, Hutter AM, Brindis RG, et al: Use of sildenafil (Viagra) in patients with cardiovascular disease. Circulation 1999;99:168-177.
110. Ghofrani HA, Rose F, Schermuly RT, et al: Oral sildenafil as long-term adjuvant to inhaled iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol 2003;42:158-164.
111. Cooke JP: A novel mechanism for pulmonary arterial hypertension? Circulation 2003;108:1420-1421.
112. Hasuda T, Satoh T, Shimouki A, et al: Improvement in exercise capacity with nitric oxide inhalation in patients with precapillary pulmonary hypertension. Circulation 2000;101:2066-2070.
113. Sitbon O, Brenot F, Denjean A, et al: Inhaled nitric oxide as screening vasodilator in primary pulmonary hypertension: a dose-response study and comparison with prostacyclin. Am J Respir Crit Care Med 1995;151:384-389.
114. Parker DDI, Doran A, Parker D, Kinsella JP, Abman SH: Acute hemodynamic effects and home therapy using a novel pulsed nasal nitric oxide delivery system in children and young adults with pulmonary hypertension. Am J Cardiol 2003;92:886-890.
115. Champion HC, Bivalacqua TJ, Greenberg SS, et al: Adenoviral gene transfer of endothelial nitric-oxide synthetase (eNOS) partially restores normal pulmonary arterial pressure in eNOS-deficient mice. Proc Natl Acad Sci USA 2002;99:13248-13253.
116. Wagner F, Dandel M, Günther G, et al: Nitric oxide inhalation in the treatment of right ventricular dysfunction following left ventricular assist device implantation. Circulation 1997;9:II-291-296.
117. Wessel DL, Adiata I, Giglia TM, et al: Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass. Circulation 1993;88:2128-2138.
118. Moncada S, Higgs A: The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002-2012.
119. Mehta S, Stewart DJ, Langleben D, et al: Short term pulmonary vasodilation with L-arginine in pulmonary hypertension. Circulation 1995;92:1539-1545.
120. Boerger RH, Mugge A, Bode-Boerger SM, et al: Differential systemic and pulmonary hemodynamic effects of L-arginine in patients with coronary artery disease or primary pulmonary hypertension. Int J Clin Pharmacol Ther 1996;34:323-328.
121. Nagaya N, Uematsu M, Oya H, et al: Short term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. Am J Respir Crit Care Med 2001;163:887-891.
122. Hoeper MM, Taha N, Bekjarova A, Gatzke R, Spiekerkotter E: Bosentan treatment in patients with primary pulmonary hypertension receiving nonparenteral prostanoids. Eur Respir J 2003;22:330-334.
123. Ueno M, Miyauchi T, Sakai S Goto K, Yamaguchi I: Endothelin-A-receptor antagonist and oral prostacyclin analog are comparable effective in ameliorating pulmonary hypertension and right-ventricular hypertrophy in rats. J Cardiovasc Pharmacol 2000;36(5 suppl 1):S305-S310.
124. Ueno M, Miyauchi T, Sakai S, et al: A combination of oral endothelin-A-receptor antagonist and oral prostacyclin analogue is superior to each drug alone in ameliorating pulmonary hypertension in rats. J Am Coll Cardiol 2002;40:175-181.
125. Wilkens H, Guth A, Konig JF, et al: Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation 2001;104:1218-1222.
126. Ghofrani HA, Wiedemann R, Rose F, et al: Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 2002;136:515-522.
127. Channick RN, Sitbon O, Barst JB, Manes A, Rubin LJ: Endothelin receptor antagonists in pulmonary arterial hypertension. J Am Coll Cardiol 2004;43/12(suppl S):62S-67S.
128. Garcia HFJ, Ocana MC, Mateos RL, et al: Combined treatment with intravenous prostacyclin and sildenafil in patients with pulmonary hypertension: report of cases. Med Clin (Barc) 2004;122:64-66.
129. Ghofrani HA, Rose F, Schermuly RT, et al: Amplification of the pulmonary vasodilatory response to inhaled iloprost by subthreshold phosphodiesterase types 3 and 4 inhibition in severe pulmonary hypertension. Crit Care Med 2002;30:2489-2492.
130. Ghofrani HA, Rose F, Schermuly RT, et al: Oral sildenafil as long-term adjuvant therapy to inhaled iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol 2003;42:158-164.
131. Ziesche R, Petkov V, Wittmann K, et al: Treatment with epoprostenol reverts nitric oxide non-responsiveness in patients with primary pulmonary hypertension. Heart 2000;83:406-409.
132. Ghofrani HA, Pepke-zaba J, Barbera JA, et al: Nitric oxide pathway and phosphodiesterase inhibition in pulmonary arterial hypertension. J Am Coll Cardiol 2004;43(suppl S):68S-72S.
133. Ichida F, Uese K, Tsubata S, et al: Additive effect of beraprost on pulmonary vasodilation by inhaled nitric oxide in children with pulmonary hypertension. Am J Cardiol 1997;80:662-664.
134. Rimsberger PC, Spahr-Schöpfer I, Berner M, et al: Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease: vasodilator capacity and cellular mechanism. Circulation 2001;103:544-548.
135. Ng C, Franklin O, Vaidya M, Pierce C, Petos A: Adenosine infusion for the management of persistent pulmonary hypertension of the newborn. Pediatr Crit Care Med 2004;5:10-13.
136. Ewert R, Wensel C, Opitz C, et al: Prognosis in patients with primary pulmonary hypertension awaiting lung transplantation. Transplant Proc 2001;33:3574-3575.
137. Dandel M, Kemper Y, Weng Y, et al: Primary pulmonary hypertension: survival benefits of therapy with prostacyclin analogues and transplantation. Transplant Proc 2003;35:2117-2120.
138. Dandel M, Hetzer R: Clinical value of prostacyclin and ist analogs in the management of pulmonary arterial hypertension. Curr Vasc Pharmacol 2003;1:171-181.
139. Galie N, Seeger W, Naeije R, Simmoneau G, Rubin LJ: Comparative analysis of clinical trials and evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol 2004;43(suppl S):81S-88S.
140. Badesch DB, McLaughlin VV, Delcroix M, et al: Prostanoid therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2004;43(suppl S):56S-61S.