Advertisement

Pharmacological Treatment of Pulmonary Hypertension

  • Mary P. Mullen
  • David L. Wessel
Chapter
  • 1.1k Downloads

Elevated pulmonary arterial pressure arises from three well-characterized vascular changes: vasoconstriction, thrombus formation, or proliferation of smooth muscle and/or endothelial cells in the pulmonary vessels. Thus, pulmonary hypertension is associated with conditions causing chronic vasoconstriction, thrombosis, or abnormalities of vessel function.

Keywords

Nitric Oxide Nitric Oxide Pulmonary Hypertension Congenital Heart Disease Pulmonary Arterial Hypertension 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Farber HW, Loscalzo J. Pulmonary arterial hypertension. New England Journal of Medicine 351(16):1655–1665, 2004.PubMedGoogle Scholar
  2. 2.
    Hassoun PM, Thappa V, Landman MJ, Fanburg BL. Endothelin 1: mitogenic activity on pulmonary artery smooth muscle cells and release from hypoxic endothelial cells. Proceedings of the Society for Experimental Biology & Medicine 1992;165–170.Google Scholar
  3. 3.
    Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327:524–526.PubMedGoogle Scholar
  4. 4.
    Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A 1987; 84:9265–9269.PubMedGoogle Scholar
  5. 5.
    Heath D, Edwards JE. The pathology of hypertensive pulmonary vascular disease: a description of six grades of structural changes in the pulmonary arteries with special attention to congenital cardiac septal defects. Circulation 1958; 18:533–547.PubMedGoogle Scholar
  6. 6.
    Celermajer DS, Cullen S, Deanfield JE. Impairment of endothelium-dependent pulmonary artery relaxation in children with congenital heart disease and abnormal pulmonary hemodynamics. Circulation 1993; 87:440–446.PubMedGoogle Scholar
  7. 7.
    Haworth SG. Normal pulmonary vascular development and its disturbance in congenital heart disease. 1981.Google Scholar
  8. 8.
    Adatia I, Barrow SE, Stratton PD, Miall-Allen VM, Ritter JM, Phil D, et al. Thromboxane A2 and prostacyclin biosynthesis in children and adolescents with pulmonary vascular disease. Circulation 1993; 88[part 1]:2117–2122.Google Scholar
  9. 9.
    Adatia I, Haworth SG. Circulating endothelin in children with congenital heart disease. Br Heart J 1993; 69:233–236.PubMedGoogle Scholar
  10. 10.
    Adatia I, Barrow SE, Stratton PD, Ritter JM, Haworth SG. Effect of intracardiac repair on thromboxane A2 and prostaglandin biosynthesis in children with left to right shunt. Br Heart J 1994; 72:452–456.PubMedGoogle Scholar
  11. 11.
    Canter J, Summar ML, Smith HB, et al. Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: A validated genetic association study. Mitochondrion 2007; 7(3):204–210.PubMedGoogle Scholar
  12. 12.
    Wessel DL. Current and future strategies in the treatment of childhood pulmonary hypertension. Prog Ped Cardiol 2001; 12:289.Google Scholar
  13. 13.
    Hopkins RA, Bull C, Haworth SG, De Leval MR, Stark J. Pulmonary hypertensive crises following surgery for congenital heart defects in young children. European Journal of Cardio-Thoracic Surgery 1991; 5(12):628–634.PubMedGoogle Scholar
  14. 14.
    Lindberg L, Olsson AK, Jogi P, Jonmarker C. How common is severe pulmonary hypertension after pediatric cardiac surgery? The Journal Of Thoracic And Cardiovascular Surgery 2002; 123:1155–1163.PubMedGoogle Scholar
  15. 15.
    Schulze-Neick I, Li J, Penny DJ, Redington AN. Pulmonary vascular resistance after cardiopulmonary bypass in infants: effect on postoperative recovery. The Journal Of Thoracic And Cardiovascular Surgery 2001; 121:1033–1039.PubMedGoogle Scholar
  16. 16.
    Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288:373–376.PubMedGoogle Scholar
  17. 17.
    Ignarro LJ, Buga GM, Woods KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci 1987; 84:9265–9269.PubMedGoogle Scholar
  18. 18.
    Palmer RMJ, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988; 333:664–666.PubMedGoogle Scholar
  19. 19.
    Day R, Lynch J, Shaddy R, Orsmond G. Pulmonary vasodilatory effects of 12 and 60 parts per million inhaled nitric oxide in children with ventricular septal defect. Am J Cardiol 1995; 75:196–198.PubMedGoogle Scholar
  20. 20.
    Adatia I, Perry S, Landzberg M, Moore P, Thompson JE, Wessel DL. Inhaled nitric oxide and hemodynamic evaluation of patients with pulmonary hypertension before transplantation. J Am Coll Cardiol 1995; 25:1656–1664.PubMedGoogle Scholar
  21. 21.
    Atz AM, Adatia I, Jonas RA, Wessel DL. Inhaled nitric oxide in children with pulmonary hypertension and congenital mitral stenosis. Am J Cardiol 1996; 77:316–319.PubMedGoogle Scholar
  22. 22.
    Wessel DL, Adatia I, Giglia TM, Thompson JE, Kulik TJ. Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass. Circulation 1993; 88:2128–2138.PubMedGoogle Scholar
  23. 23.
    Roberts JD, Jr., Lang P, Bigatello LM, Vlahakes GJ, Zapol WM. Inhaled nitric oxide in congenital heart disease. Circulation 1993; 87:447–453.PubMedGoogle Scholar
  24. 24.
    Adatia I, Lillehei C, Arnold JH, Thompson JE, Palazzo R, Fackler JC, et al. Inhaled nitric oxide in the treatment of postoperative graft dysfunction after lung transplantation. Annals of Thoracic Surgery 1994; 57(5):1311–1318.PubMedGoogle Scholar
  25. 25.
    Roberts JD, Polaner DM, Lang P, Zapol WM. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992; 340:818–819.PubMedGoogle Scholar
  26. 26.
    Kinsella JP, Neish SR, Ivy DD, Shaffer E, Abman SH. Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide. J Pediatr 1993; 123:103–108.PubMedGoogle Scholar
  27. 27.
    Finer NN, Etches PC, Kamstra B, Tierney AJ, Peliowski A, Ryan CA. Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: dose response. J Pediatr 1994; 124:302–308.PubMedGoogle Scholar
  28. 28.
    Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM. Inhaled nitric oxide for the adult respiratory distress syndrome. New England Journal of Medicine 1993; 328:399–405.PubMedGoogle Scholar
  29. 29.
    Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 1989; 2:997–1000.PubMedGoogle Scholar
  30. 30.
    Cremona G, Dinh-Xuan AT, Higenbottam TW. Endothelium-derived relaxing factor and the pulmonary circulation. Lung 1991; 169:185–202.PubMedGoogle Scholar
  31. 31.
    Turner-Gomes SO, Andrew M, Coles J, Trusler GA, Williams WG, Rabinovitch M. Abnormalities in von Willebrand factor and antithrombin III after cardiopulmonary bypass operations for congenital heart disease. Journal of Thoracic & Cardiovascular Surgery 1992; 103(1):87–97.Google Scholar
  32. 32.
    Kirshbom MP, Jacobs TM, Tsui SLSDRL, Schwinn AD, Ungerleider MR, Gaynor WJ. Effects of cardiopulmonary bypass and circulatory arrest on endothelium-dependent vasodilatation in the lung. J Thorac Cardiovasc Surg 1996; 111:1248–1256.PubMedGoogle Scholar
  33. 33.
    Koul B, Willen H, Sjöberg T, Wetterberg T, Kugelberg J, Steen S. Pulmonary sequelae of prolonged total venoarterial bypass: Evaluation with a new experimental model. Ann Thorac Surg 1991; 51:794–799.PubMedGoogle Scholar
  34. 34.
    Beghetti M, Silkoff PE, Caramori M, Holtby HM, Slutsky AS, Adatia I. Decreased exhaled nitric oxide may be a marker of cardiopulmonary bypass-induced injury. Ann Thorac Surg 1998; 66:532–534.PubMedGoogle Scholar
  35. 35.
    Rimar S, Gillis CN. Pulmonary vasodilation by inhaled nitric oxide after endothelial injury. Journal of Applied Physiology 1992; 73(5):2179–2183.PubMedGoogle Scholar
  36. 36.
    Hillier SC, Graham JA, Hanger CC, Wagner WW, Jr. Inhaled nitric oxide reverses hypoxic vasoconstriction in <100 micron canine pulmonary microvessels. Anesth Analg 1995; 80:S187.Google Scholar
  37. 37.
    Roos CM, Rich GF, Uncles DR, Daugherty MO, Frank DU. Sites of vasodilation by inhaled nitric oxide vs. sodium nitroprusside in endothelin-constricted isolated rat lungs. Journal of Applied Physiology 1994; 77(1):51–57.PubMedGoogle Scholar
  38. 38.
    Gao Y, Zhou H, Raj JU. Endothelium-derived nitric oxide plays a larger role in pulmonary veins than in arteries of newborn lambs. Circ Res 1995; 76:559–565.PubMedGoogle Scholar
  39. 39.
    Mikiyasu S, Shimouchi A, Kawaguchi AT, Ninomiya I. Inhaled nitric oxide: diameter response patterns in feline small pulmonary arteries and veins. Am J Physiol 1996; 270:H974–H980.Google Scholar
  40. 40.
    Rimar S, Gillis CN. Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung. Journal of Applied Physiology 1995; 78(5):1745–1749.PubMedGoogle Scholar
  41. 41.
    Benzing A, Geiger K. Inhaled nitric oxide lowers pulmonary capillary pressure and changes longitudinal distribution of pulmonary vascular resistance in patients with acute lung injury. Acta Anaesthesiol Scand 1994; 38:640–645.PubMedGoogle Scholar
  42. 42.
    Wheller J, George BL, Mulder DG, Jarmakani JM. Diagnosis and management of postoperative pulmonary hypertensive crisis. Circulation 1979; 60:1640–1644.PubMedGoogle Scholar
  43. 43.
    Del Nido PJ, Williams WG, Villamater J, Benson LN, Coles JG, Bohn D, et al. Changes in pericardial surface pressure during pulmonary hypertensive crises after cardiac surgery. Circulation 1987; 76[suppl III]:93.Google Scholar
  44. 44.
    Journois D, Pouard P, Mauriat P, Malhère T, Vouhe P, Safran D. Inhaled nitric oxide as a therapy for pulmonary hypertension after operations for congenital heart defects. J Thorac Cardiovasc Surg 1994; 107:1129–1135.PubMedGoogle Scholar
  45. 45.
    Journois D, Baufreton C, Mauriat P, Pouard P, Vouh P, Safran D. Effects of inhaled nitric oxide administration on early postoperative mortality in patients operated for correction of atrioventricular canal defects. Chest 2005; 128:3537–3544.PubMedGoogle Scholar
  46. 46.
    Schaffer R, Berdat P, Stolle B, Pfammatter JP, Stocker F, Carrel T. Surgery of the complete atrioventricular canal: relationship between age at operation, mitral regurgitation, size of the ventricular septum defect, additional malformations and early postoperative outcome. Cardiology 1999; 91:231–235.PubMedGoogle Scholar
  47. 47.
    Bizzarro M, Gross I. Inhaled nitric oxide for the postoperative management of pulmonary hypertension in infants and children with congenital heart disease. Cochrane Database Of Systematic Reviews 2005;CD005055.Google Scholar
  48. 48.
    Dyar O, Young JD, Xiong L, Howell S, Johns E. Dose-response relationship for inhaled nitric oxide in experimental pulmonary hypertension in sheep. Br J Anaesth 1993; 71:702–708.PubMedGoogle Scholar
  49. 49.
    Sitbon O, Brenot F, Denjean A, Bergeron A, Parent F, Azarian R, et al. Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension. A dose-response study and comparison with prostacyclin. American Journal of Respiratory & Critical Care Medicine 1995; 151(2 Pt 1):384–389.Google Scholar
  50. 50.
    Gerlach H, Rossaint D, Pappert D, Falke KJ. Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome. Euro J Clin Invest 1993; 23:499–502.Google Scholar
  51. 51.
    Puybasset L, Rouby JJ, Mourgeon E, Stewart TE, Cluzel P, Arthaud M, et al. Inhaled nitric oxide in acute respiratory failure: dose-response curves. Int Care Med 1994; 20:319–327.Google Scholar
  52. 52.
    Lonnqvist PA, Jonsson B, Winberg P, Frostell CG. Inhaled nitric oxide in infants with developing or established chronic lung disease. Acta Paediatr 1995; 84:1188–1192.PubMedGoogle Scholar
  53. 53.
    DeMarco V, Skimming JW, Ellis TM, Cassin S. Nitric oxide inhalation: effects on the ovine neonatal pulmonary and systemic circulations. Reproduction, Fertility & Development 1996; 8:431–438.Google Scholar
  54. 54.
    Rich GF, Roos CM, Anderson SM, Urich DC, Daugherty MO, Johns RA. Inhaled nitric oxide: dose response and the effects of blood in the isolated rat lung. Journal of Applied Physiology 1993; 75(3):1278–1284.PubMedGoogle Scholar
  55. 55.
    Berger JI, Gibson RL, Redding GJ, Standaert TA, Clarke WR, Truog WE. Effect of inhaled nitric oxide during group B streptococcal sepsis in piglets. Am Rev Respir Dis 1993; 147:1080–1086.PubMedGoogle Scholar
  56. 56.
    Maruyama K, Kobayasi H, Taguchi O, Chikusa H, Muneyuki M. Higher does of inhaled nitric oxide might be less effective in improving oxygenation in a patient with interstitial pulmonary fibrosis. Anesth Analg 1995; 81:210–211.PubMedGoogle Scholar
  57. 57.
    Buhrer C, Merker G, Falke K, Versmold H, Obladen M. Dose-response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: a preliminary report. Pediatric Pulmonology 1995; 19:291–298.PubMedGoogle Scholar
  58. 58.
    Demirakca S, Dotsch J, Knothe C, Magsaam J, Reiter HL, Bauer J, et al. Inhaled nitric oxide in neonatal and pediatric acute respiratory distress syndrome: Dose response, prolonged inhalation, and weaning. Crit Care Med 1996; 24:1913–1919.PubMedGoogle Scholar
  59. 59.
    Young JD, Sear JW, Valvini EM. Kinetics of methaemoglobin and serum nitrogen oxide production during inhalation of nitric oxide in volunteers. Br J Anaesth 1996; 76:652–656.PubMedGoogle Scholar
  60. 60.
    Rimar S, Gillis CN. Selective pulmonary vasodilation by inhaled nitric oxide is due to hemoglobin inactivation. Circulation 1993; 88:2884–2887.PubMedGoogle Scholar
  61. 61.
    Hallman M, Bry K, Lappalainen U. A mechanism of nitric oxide-induced surfactant dysfunction. J Appl Physiol 1996; 80:2035–2043.PubMedGoogle Scholar
  62. 62.
    Semigran MJ, Cockrill BA, Kacmarek R, Thompson BT, Zapol WM, Dec GW, et al. Hemodynamic effects of inhaled nitric oxide in heart failure. J Am Coll Cardiol 1994; 24:982–988.PubMedGoogle Scholar
  63. 63.
    Loh E, Stamler JS, Hare JM, Loscalzo J, Colucci WS. Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction. Circulation 1994; 90:2780–2785.PubMedGoogle Scholar
  64. 64.
    Bocchi EA, Bacal F, Auler Junior JO, Carmone MJ, Bellotti G, Pileggi F. Inhaled nitric oxide leading to pulmonary edema in stable severe heart failure. Am J Cardiol 1994; 74:70–72.PubMedGoogle Scholar
  65. 65.
    Hare JM, Shernan SK, Body SC, Graydon E, Colucci WS, Couper GS. Influence of inhaled nitric oxide on systemic flow and ventricular filling pressure in patients receiving mechanical circulatory assistance. Circulation 1997; 95:2250–2253.PubMedGoogle Scholar
  66. 66.
    Atz AM, Adatia I, Wessel DL. Rebound pulmonary hypertension after inhalation of nitric oxide. Ann Thorac Surg 1996; 62:1759–1764.PubMedGoogle Scholar
  67. 67.
    Francoise M, Gouyon JB, Mercier JC. Hemodynamic and oxygenation changes induced by the discontinuation of low-dose inhalational nitric oxide in newborn infants. Int Care Med 1996; 22:477–481.Google Scholar
  68. 68.
    Miller OI, Tang SF, Keech A, Celermajer DS. Rebound pulmonary hypertension on withdrawal from inhaled nitric oxide. Lancet 1995; 346:51–52.PubMedGoogle Scholar
  69. 69.
    Lavoie A, Hall JB, Olson DM, Wylam ME. Life-threatening effects of discontinuing inhaled nitric oxide in severe respiratory failure. Am J Respir Crit Care Med 1996; 153:1985–1987.PubMedGoogle Scholar
  70. 70.
    Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology 1999; 91(1):307–310.PubMedGoogle Scholar
  71. 71.
    Tweddell JS, Hoffman GM, Fedderly RT, Berger S, Thomas JP Jr, Ghanayem NS, et al. Phenoxybenzamine improves systemic oxygen delivery after the Norwood procedure. The Annals of Thoracic Surgery 1999; 67:161.PubMedGoogle Scholar
  72. 72.
    Bando K, Turrentine MW, Sharp TG, Sekine Y, Aufiero TX, Sun K, et al. Pulmonary hypertension after operations for congenital heart disease: analysis of risk factors and management. The Journal Of Thoracic And Cardiovascular Surgery 1996; 112:1600.PubMedGoogle Scholar
  73. 73.
    Kiran U, Makhija N, Das SN, Bhan A, Airan B. Combination of phenoxybenzamine and nitroglycerin: effective control of pulmonary artery pressures in children undergoing cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia 2005; 19:274–275.PubMedGoogle Scholar
  74. 74.
    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.PubMedGoogle Scholar
  75. 75.
    Olschewski H, Walmrath D, Schermuly R, Ghofrani HA, Grimminger F, Seeger W. Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann Intern Med 1996; 124:820–824.PubMedGoogle Scholar
  76. 76.
    Zobel G, Dacar D, Rodl S, Friehs I. Inhaled nitric oxide versus inhaled prostacyclin and intravenous versus inhaled prostacyclin in acute respiratory failure with pulmonary hypertension in piglets. Pediatr Res 1995; 38:198–204.PubMedGoogle Scholar
  77. 77.
    Zwissler B, Welte M, Messmer K. Effects of inhaled prostacyclin as compared with inhaled nitric oxide on right ventricular performance in hypoxic pulmonary vasoconstriction. Journal Of Cardiothoracic And Vascular Anesthesia 1995; 9:283–289.PubMedGoogle Scholar
  78. 78.
    Goldman AP, Delius RE, Deanfield JE, Macrae DJ. Nitric oxide is superior to prostacyclin for pulmonary hypertension after cardiac operations. Annals of Thoracic Surgery 1995; 60(2):300–305.PubMedGoogle Scholar
  79. 79.
    Carroll CL, Backer CL, Mavroudis C, Cook K, Goodman DM. Inhaled prostacyclin following surgical repair of congenital heart disease—a pilot study. Journal Of Cardiac Surgery 2005; 20:436–439.PubMedGoogle Scholar
  80. 80.
    Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, et al. Inhaled iloprost for severe pulmonary hypertension. New England Journal of Medicine 2002; 347(5):322–329.PubMedGoogle Scholar
  81. 81.
    Max M, Rossaint R. Inhaled prostacyclin in the treatment of pulmonary hypertension. European Journal of Pediatrics 1999; 158:S23–S26.PubMedGoogle Scholar
  82. 82.
    Hoeper MM, Schwarze M, Ehlerding S, Adler-Schuermeyer A, Spiekerkoetter E, Niedermeyer J, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. New England Journal of Medicine 2000; 342:1866–1870.PubMedGoogle Scholar
  83. 83.
    Rimensberger PC, Spahr-Schopfer I, Berner M, Jaeggi E, Kalangos A, Friedli B, et al. Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease: vasodilator capacity and cellular mechanisms. Circulation 2001; 103:544–548.PubMedGoogle Scholar
  84. 84.
    Hoeper MM, Spiekerkoetter E, Westerkamp V, Gatzke R, Fabel H. Intravenous iloprost for treatment failure of aerosolised iloprost in pulmonary arterial hypertension. The European Respiratory Journal: Official Journal Of The European Society For Clinical Respiratory Physiology 2002; 20:339–343.Google Scholar
  85. 85.
    Parker TA, Ivy DD, Kinsella JP, Torielli F, Ruyle SZ, Thilo EH, et al. Combined therapy with inhaled nitirc oxide and intravenous prostacyclin in an infant with alveolar-capillary dysplasia. American Journal Of Respiratory And Critical Care Medicine 1997; 155:743–746.PubMedGoogle Scholar
  86. 86.
    Schranz D, Huth R, Wippermann CF, Ritzerfeld S, Schmitt FX, Oelert H. Nitric oxide and prostacyclin lower suprasystemic pulmonary hypertension after cardiopulmonary bypass. European Journal of Pediatrics 1993; 152:793–796.PubMedGoogle Scholar
  87. 87.
    Ivy DD, Kinsella JP, Wolfe RR, Abman SH. Atrial natriuretic peptide and nitric oxide in children with pulmonary hypertension after surgical repair of congenital heart disease. Am J Cardiol 1996; 77:102–105.PubMedGoogle Scholar
  88. 88.
    Kinsella JP, Torielli F, Ziegler JW, Ivy DD, Abman SH. Dipyrimadole augmentation of response to nitric oxide. Lancet 1995; 346:647–648.PubMedGoogle Scholar
  89. 89.
    Fullerton DA, Jaggers J, Piedalue F, Grover FL, McIntyre RC. Effective control of refractory pulmonary hypertension after cardiac operations. J Thorac Cardiovasc Surg 1997; 113:363–368.PubMedGoogle Scholar
  90. 90.
    Cohen AH, Hanson K, Morris K, Fouty B, McMurtry IF, Clarke W, et al. Inhibition of cyclic 3.-5–guanosine monophosphate-specific phosphodiesterase selectively vasodilates the pulmonary circulation in chronically hypoxic rats. J Clin Invest 1996; 97:172–179.PubMedGoogle Scholar
  91. 91.
    Gatecel C, Mebazaa A, Kong R, Guinard N, Kermarrec N, Mateo J, et al. Inhaled nitric oxide improves hepatic tissue oxygenation in right ventricular failure: value of venous oxygen saturation monitoring. Anesth 1995; 82:588–590.Google Scholar
  92. 92.
    Yahagi N, Kumon K, Nakatani T, Matsui J, Sasako Y, Isobe F, et al. Inhaled nitric oxide for the management of acute right ventricular failure in patients with a left ventricular assist system. Artif Organs 1995; 19:557–558.PubMedGoogle Scholar
  93. 93.
    Humpl T, Reyes JT, Holtby H, Stephens D, Adatia I. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation 2005; 111:3274–3280.PubMedGoogle Scholar
  94. 94.
    Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesth 1999; 91:307–310.Google Scholar
  95. 95.
    Atz AM, Lefler AK, Fairbrother DL, Uber WE, Bradley SM. Sildenafil augments the effect of inhaled nitric oxide for postoperative pulmonary hypertensive crises. The Journal Of Thoracic And Cardiovascular Surgery 2002; 124:628–629.PubMedGoogle Scholar
  96. 96.
    Namachivayam P, Theilen U, Butt WW, Cooper SM, Penny DJ, Shekerdemian LS. Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. American Journal Of Respiratory And Critical Care Medicine 2006; 174:1042–1047.PubMedGoogle Scholar
  97. 97.
    Channick RN, Rubin LJ. Combination therapy for pulmonary hypertension: a glimpse into the future? [comment]. Critical Care Medicine 2000; 28(3):896–897.PubMedGoogle Scholar
  98. 98.
    D’Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Annals of Internal Medicine 1991; 115(5):343–349.PubMedGoogle Scholar
  99. 99.
    Yung D, Widlitz AC, Rosenzweig EB, Kerstein D, Maislin G, Barst RJ. Outcomes in children with idiopathic pulmonary arterial hypertension. Circulation 2004; 110(6):660–665.PubMedGoogle Scholar
  100. 100.
    Badesch DB, Abman SH, Ahearn GS, Barst RJ, McCrory DC, Simonneau G, et al. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126(1 Suppl):35S–62S.PubMedGoogle Scholar
  101. 101.
    Fuster V, Steele PM, Edwards WD, Gersh BJ, McGoon MD, Frye RL. Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 1984; 70(4):580–587.PubMedGoogle Scholar
  102. 102.
    Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. New England Journal of Medicine 1992; 327:76–81.PubMedGoogle Scholar
  103. 103.
    Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for primary pulmonary hypertension in children. Circulation 1999; 99:1197–1208.PubMedGoogle Scholar
  104. 104.
    Sandoval J, Bauerle O, Gomez A, Palomar A, Martinez Guerra ML, Furuya ME. Primary pulmonary hypertension in children: clinical characterization and survival. Journal of the American College of Cardiology 1995; 25(2):466–474.PubMedGoogle Scholar
  105. 105.
    Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF, 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.PubMedGoogle Scholar
  106. 106.
    Barst RJ, Ivy D, Dingemanse J, Widlitz A, Schmitt K, Doran A, et al. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clinical Pharmacology & Therapeutics 2003; 73(4):372–382.Google Scholar
  107. 107.
    Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. The New England Journal of Medicine 2005; 353:2148–2157.PubMedGoogle Scholar
  108. 108.
    Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. [Review] [97 refs]. New England Journal of Medicine 2004; 351(14):1425–1436.PubMedGoogle Scholar
  109. 109.
    Saygili A, Canter B, Iriz E, Kula S, Tunao lu FS, Olguntürk R, Ozdo an ME. Use of sildenafil with inhaled nitric oxide in the management of severe pulmonary hypertension. J Cardiothorac Vasc Anesth 2004; 18:775–776.PubMedGoogle Scholar
  110. 110.
    Zhao L, Mason NA, Morrell NW, Kojonazarov B, Sadykov A, Maripov A, et al. Sildenafil inhibits hypoxia-induced pulmonary hypertension. Circulation 2001; 104(4):424–428.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2008

Authors and Affiliations

  • Mary P. Mullen
    • 1
  • David L. Wessel
    • 1
  1. 1.Department of Cardiac Intensive CareChildren's Hospital BostonBostonUSA

Personalised recommendations