Pathophysiology, diagnosis, and management of pulmonary hypertension in infants and children

Journal of Intensive Care Medicine

Volumn 11, Issue 2, 1996, Pages 90-107

  Baff, Jeanne M ^a   Gordon, John B ^a,b  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MARYLAND MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMRINONE; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; CALCIUM CHANNEL BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; NITROPRUSSIDE SODIUM; PROSTACYCLIN; PROSTAGLANDIN E1; SALBUTAMOL; TOLAZOLINE; VASODILATOR AGENT;

ANIMAL MODEL; BLOOD VESSEL REACTIVITY; CHILD; CHILDHOOD DISEASE; CLINICAL TRIAL; CONGENITAL HEART DISEASE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DISEASE SEVERITY; ECHOCARDIOGRAPHY; ELECTROCARDIOGRAPHY; GASTROINTESTINAL HEMORRHAGE; HEART CATHETERIZATION; HUMAN; INFANT; INHALATIONAL DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; LUNG ARTERY; LUNG BIOPSY; LUNG VASCULAR RESISTANCE; LUNG VENTILATION; MULTICENTER STUDY; NEWBORN; NONHUMAN; ORAL DRUG ADMINISTRATION; PAIN; PHOTOSENSITIVITY; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RANDOMIZED CONTROLLED TRIAL; REVIEW;

EID: 0029869825     PISSN: 08850666     EISSN: None     Source Type: Journal    
DOI: 10.1177/088506669601100203     Document Type: Review

References (199)

1. Marshall BE, Marshall C. Pulmonary hypertension. In: Crystal RG, West JB, eds. The lung. New York: Raven, 1991:1177-1188
2. Pongpanich B, Ritter DG, Ongley PA. Hemodynamic findings in children without significant heart disease. Mayo Clin Proc. 1969;44:13-24
3. Krovetz LJ, Goldbloom S. Normal standards for cardiovascular data II. Pressure and vascular resistances. Johns Hopkins Med J 1972;130:187-95
4. Gordon JB. Developmental physiology of the pulmonary circulation. In: Stidham GL, Weigle CGM, eds. Pediatric critical care clinical review series - part 2. New York, NY: Society for Critical Care Medicine, 1993: 1-14
5. Soifer SJ. Pulmonary hypertension: physiologic or pathologic disease. Crit Care Med 1993;21:S370-374
6. West JB. Ventilation/blood flow and gas exchange, ed 3. Osney Mead, Oxford: Blackwell Scientific, 1977:1-113
7. Rudolph AM. High pulmonary vascular resistance after birth. Clin Pediatr 1980;19:585-590
8. Cassin S, Dawes GS, Mott JC, et al. The vascular resistance of the fetal and newly ventilated lung of the lamb. J Physiol [Lond] 1964;171:61-79
9. Campbell AGM, Cockburn F, Dawes GS, Milligan JE. Pulmonary vasoconstriction in asphyxia during cross-circulation between twin foetal lambs. J Physiol [Lond] 1967; 192:111-121
10. Heymann MA, Rudolph AM, Nies AS, Melmon KL. Bradykinin production associated with oxygenation of the fetal lamb. Circ Res 1969;25:521-533
11. Murphy JD, Vawter GF, Reid LM. Pulmonary vascular disease in fatal meconium aspiration. J Pediatr 1984;104: 758-762
12. Cassin S. Role of prostaglandins, thromboxanes, and leukotrienes in the control of the pulmonary circulation in the fetus and newborn. Semin Perinatol 1987;11:53-63
13. Tod ML, Yoshimura K, Rubin LJ. Indomethacin prevents ventilation-induced decreases in pulmonary vascular resistance of the middle region in fetal lambs. Pediatr Res 1991;29:449-454
14. McQueston JA, Cornfield DN, McMurtry IF, Abman SH. Effects of oxygen and exogenous L-arginine on EDRF activity in fetal pulmonary circulation. Am J Physiol 1993;264: H865-871
15. Cornfield DN, Chatfield BA, McQueston JA, et al. Effects of birth-related stimuli on L-arginine-dependent pulmonary vasodilation in ovine fetus. Am J Physiol 1992;262: H1474-1481
16. Cornfield DN, McQueston JA, McMurtry IF, et al. Role of ATP-sensitive potassium channels in ovine fetal pulmonary vascular tone. Am J Physiol 1992;263:H1363-1368
17. Moore PK, Velvis H, Fineman JR, et al. EDRF inhibition attenuates the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs. J Appl Physiol 1992;73: 2151-2157
18. Haworth SG, Hislop AA. Adaptation of the pulmonary circulation to extra-uterine life in pigs and its relevance to the human infant. Cardiovasc Res 1981;15:108-119
19. Haworth SG, Hislop AA. Normal structural and functional adaptation to extrauterine life. J Pediatr 1981;98:915-918
20. Haworth SG. Pulmonary vascular remodeling in neonatal pulmonary hypertension. Chest 1988;93:133S-138S
21. Haworth SG, Hall SM, Chew M, Allen KM. Thinning of fetal pulmonary arterial wall and postnatal remodelling: ultrastructural studies on the respiratory unit arteries of the pig. Virch Arch [A] 1987;411:161-171
22. Allen K, Haworth SG. Human postnatal pulmonary arterial remodeling. Lab Invest 1988;59:702-709
23. Haworth SG, Hislop AA. Pulmonary vascular development: normal values of peripheral vascular structure. Am J Cardiol 1983;52:578-583
24. Michel RP, Gordon JB, Chu K. Development of the pulmonary vasculature in newborn lambs: structure-function relationships. J Appl Physiol 1991;70:1255-1264
25. Reid L. The lung: its growth and remodeling in health and disease. Am J Roentgenol 1977;129:777-788
26. Reeves JT, Leathers JE. Circulatory changes following birth of the calf and the effect of hypoxia. Circ Res 1964;15: 343-354
27. Custer JR, Hales CA. Influence of alveolar oxygen on pulmonary vasoconstriction in newborn lambs versus sheep. Am Rev Respir Dis 1985;132:326-331
28. Fike CD, Hansen TN. Hypoxic vasoconstriction increases with postnatal age in lungs from newborn rabbits. Circ Res 1987;60:297-303
29. Fike CD, Kaplowitz MR. Developmental differences in vascular responses to hypoxia in lungs of rabbits. J Appl Physiol 1994;77:507-516
30. Gordon JB, Tod ML, Wetzel RC, et al. Age-dependent effects of indomethacin on hypoxic vasoconstriction in neonatal lamb lungs. Pediatr Res 1988;23:580-584
31. Gordon JB, Hortop J, Hakim TS. Developmental effects of hypoxia and indomethacin on distribution of vascular resistances in lamb lungs. Pediatr Res 1989;26:325-329
32. Owen-Thomas JB, Reeves JT. Hypoxia and pulmonary artery pressure in the rabbit. J Physiol (Lond) 1969;201: 665-672
33. Belik J, Halayko A, Rao K, Stephens NL. Pulmonary vascular smooth muscle: biochemical and mechanical developmental changes. J Appl Physiol 1991;71:1129-1135
34. Rendas A, Branthwaite M, Lennox S, Reid L. Response of the pulmonary circulation to acute hypoxia in the growing pig. J Appl Physiol 1982;52:811-814
35. Rabinovitch M, Gamble W, Nadas AS, et al. Rat pulmonary circulation after chronic hypoxia: hemodynamic and structural features. Am J Physiol 1979;236:H818-H827
36. Newman JH, Souhrada JF, Reeves JT, et al. Postnatal changes in response of canine neonatal pulmonary arteries to histamine. Am J Physiol 1979;237:H76-H82
37. Redding GJ, McMurtry IF, Reeves JT. Effects of meclofenamate on pulmonary vascular resistance correlate with postnatal age in young piglets. Pediatr Res 1984;18:579-583
38. Gordon JB, Clément De Cléty S, Chu K. Development changes in effects of histamine on segmental pulmonary vascular resistances. J Appl Physiol 1991;71:150-158
39. Martinez F, Tod ML, Gordon JB. Effects of baseline resistance on developmental changes in responses to endothelium-dependent and -independent vasodilators in lamb lungs. Am Rev Respir Dis 1993;147:A417
40. w-nitro-L-arginine on total and segmental vascular resistances in developing lamb lungs. J Appl Physiol 1993;75:76-85
41. Steinhorn RH, Morin FC III, Gugino SF, et al. Developmental differences in endothelium-dependent responses in isolated ovine pulmonary arteries and veins. Am J Physiol 1993;264:H2162-H2167
42. w-nitro-L-arginine attenuates endothelium-dependent pulmonary vasodilation in lambs. Am J Physiol 1991;260:H1299-H1306
43. Burrows FA, Klinck JR, Rabinovitch M, Bohn DJ. Pulmonary hypertension in children: perioperative management. Can Anaesth Soc J 1986;33:606-628
44. Perkin RM, Anas NG. Pulmonary hypertension in pediatric patients. J Pediatr 1984;105:511-522
45. Rabinovitch M. New developments in the pathogenesis of pulmonary hypertension in the newborn and child. Acta Paediatr Jpn 1989;31:631-640
46. Rabinovitch M. Pulmonary hypertension. In: Adams FH, Emmanioulides GC, Riemenschneider TA, eels. Heart disease in infants, children and adolescents. Baltimore, MD: Williams & Wilkens, 1989:856-886
47. Hall SM, Haworth SG. Onset and evolution of pulmonary vascular disease in young children: abnormal postnatal remodelling studied in lung biopsies. J Pathol 1992;166: 183-193
48. Shrivastava S, Tandon R. Severity of rheumatic mitral stenosis in children. Int J Cardiol 1991;30:163-167
49. Paridon SM. Consequences of chronic hypoxemia and pulmonary vascular disease. In: Carson A, Bricker JT, McNamara DG, eds. The science and practice of pediatric cardiology. Philadelphia, PA: Lea and Febiger, 1990: 1996-2006
50. Zapol WM, Jones R. Vascular components of ARDS. Am Rev Respir Dis 1987;136:471-474
51. Zapol WM, Snider MT. Pulmonary hypertension in severe acute respiratory failure. N Engl J Med 1977;296:476-480
52. Rabinovitch M. Problems of pulmonary hypertension in children with congenital cardiac defects. Chest 1988;93: 119S-126S
53. Cutaia M, Rounds S. Hypoxic pulmonary vasoconstriction. Chest 1990;97:706-718
54. Fishman AP. Pulmonary circulation. In: Fishman AP, ed. The respiratory system: circulation and nonrespiratory functions, ed 2. Bethesda, MD: American Physiological Society, 1985:93-166
55. Bergofsky EH, Haas F, Porcelli R. Determination of the sensitive vascular sites from which hypoxia and hypercapnia elicit rises in pulmonaiy arterial pressure. Microcirculation 1968;27:1420-1425
56. Archer SL, McMurtry IF, Weir EK. Mechanisms of acute hypoxic and hyperoxic changes in pulmonary vascular reactivity. In: Weir EK, Reeves JT, eds. Pulmonary vascular physiology and pathophysiology. New York, NY: Marcel Dekker, 1989:241-290
57. Post JM, Hume JR, Archer SL, Weir EK. Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am J Physiol 1992;262:C882-C890
58. Cornfield DN, Stevens T, McMurtry IF, et al. Acute hypoxia causes membrane depolarization and calcium influx in fetal pulmonary artery smooth muscle cells. Am J Physiol 1994;266:L469-L475
59. Yuan X-J, Goldman WF, Tod ML, et al. Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes. J Appl Physiol 1993;264: L116-L123
60. McMurtry IF, Stanbrook HS, Rounds S. The mechanism of hypoxic pulmonary vasoconstriction: a working hypothesis. Invest Radiol 1982;77-88
61. Dawson CA. Role of pulmonary vasomotion in physiology of the lung. Physiol Rev 1984;64:544-616
62. Madden JA, Dawson CA, Harder DR. Hypoxia-induced activation in small isolated pulmonary arteries from the cat. J Appl Physiol 1985;59:113-118
63. Madden JA, Vadula MS, Kurup VP. Effects of hypoxia and other vasoactive agents on pulmonary and cerebral artery smooth muscle cells. Am J Physiol 1992;263:L384-L393
64. Hakim TS, Michel RP, Minami H, Chang HK. Site of pulmonary hypoxic vasoconstriction studied with arterial and venous occlusion. J Appl Physiol 1982;1298:1302
65. Fike CD, Gordon JB, Kaplowitz MR. Micropipette and vascular occlusion pressures in isolated lungs of newborn lambs. J Appl Physiol 1993;75:1854-1860
66. Fike CD, Kaplowitz MR. Pulmonary venous pressure increases during alveolar hypoxia in isolated lungs of newborn pigs. J Appl Physiol 1992;73:552-556
67. 2, from isolated rat lung during vasoconstriction. Circ Res 1981;48:207-213
68. u-nitro-L-arginine and pulmonary vascular pressure-flow relationship in conscious dogs. Am J Physiol 1992;262:H1331-H1337
69. Archer SL, Tolins JP, Raij L, Weir EK. Hypoxic pulmonary vasoconstriction is enhanced by inhibition of the synthesis of an endothelium derived relaxing factor. Biochem Biophys Res Commun 1989;164:1198-1205
70. Dinh-Xuan AT, Higenbottam TW, Clelland CA, et al. Impairment of pulmonary endothelium-dependent relaxation in patients with Eisenmenger's syndrome. Br J Pharmacol 1989;99:9-10
71. Dinh-Xuan AT, Higenbottam TW, Clelland CA, et al. Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease. N Engl J Med 1991;324:1539-1547
72. Adatia I, Harrow SE, Stratum P, et al. Abnormalities in the biosynthesis of thromboxane A2 and prostacyclin in children with cyanotic congenital heart disease. Br Heart J 1993;69:179-182
73. Druml W, Steltzer H, Waldhäsl W, et al. Endothelin-1 in adult respiratory distress syndrome. Am Rev Respir Dis 1993;148:1169-1173
74. Tod ML, Tseng CM, Rubin LJ. The role of eicosanoids in the pulmonary circulation. Clin Sci 1992;3:77-83
75. Macartney FJ, Panday J, Scott O. Cor pulmonale as a result of chronic nasopharyngeal obstruction due to hypertrophied tonsils and adenoids. Arch Dis Child 1969;44:585-592
76. Salvaterra CG, Rubin LJ. Investigation and management of pulmonary hypertension in chronic obstructive pulmonary disease. Am Rev Respir Dis 1993;148:1414-1417
77. Goodman G, Perkin RM, Anas NG, et al. Pulmonary hypertension in infants with bronchopulmonary dysplasia. J Pediatr 1988;112:67-72
78. Abman SH, Wolfe RR, Accurso FJ, et al. Pulmonary vascular response to oxygen in infants with severe bronchopulmonary dysplasia. Pediatrics 1985;75:80-84
79. Bush A, Busst CM, Knight WB, et al. Changes in pulmonary circulation in severe bronchopulmonary dysplasia. Arch Dis Child 1990;65:739-745
80. Heath D, Williams D, Rios-Dalenz J, et al. Small pulmonary arterial vessels of Aymara Indians from the Bolivian Andes. Histopathology 1990;16:565-571
81. Shaul PW, Farrar MA, Zellers TM. Oxygen modulates endothelium-derived relaxing factor production in fetal pulmonary arteries. Am J Physiol 1992;262:H355-H364
82. Shaul PW, Farrar MA, Magness RR. Oxygen modulation of pulmonary arterial prostacyclin synthesis is developmentally regulated. Am J Physiol 1993;265:H621-H628
83. Shaul PW, Wells LB. Oxygen modulates nitric oxide production selectively in fetal pulmonary endothelial cells. Am J Respir Cell Mol Biol 1994;11:432-438
84. Johns RA, Linden JM, Peach MJ. Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia. Circ Res 1989;65:1508-1515
85. Adnot S, Raffestin B, Eddahibi S, et al. Loss of endothelium-dependent relaxant activity in the pulmonary circulation of rats exposed to chronic hypoxia. J Clin Invest 1991; 87:155-162
86. Barnes PJ. Endothelins and pulmonary diseases. J Appl Physiol 1994;77:1051-1059
87. Stenmark KR, Aldashev AA, Orton EC, et al. Cellular adaption during chronic neonatal hypoxic pulmonary hypertension. Am J Physiol 1991;261:97-104
88. Morin FC III, Stenmark KR. Persistent pulmonary hypertension of the newborn. Am J Respir Crit Care Med 1995;151:2010-2032
89. Tiefenbrunn LJ, Riemenschneider TA. Persistent pulmonary hypertension of the newborn. Am Heart J 1986;111:564-572
90. Stenmark KR, Orton EC, Reeves JT, et al. Vascular remodeling in neonatal pulmonary hypertension. Chest 1988; 93:127S-132S
91. Stenmark KR, Abman SH, Accurso FJ. Ftiologic mechanisms in persistent pulmonary hypertension of the newborn. In: Weir EK, Reeves JT, eds. Pulmonary vascular physiology and pathophysiology. New York, NY: Marcel Dekker, 1989:355-402
92. Fike CD, Kaplowitz MR. Effect of chronic hypoxia on pulmonary vascular pressures in isolated lungs of newborn pigs. J Appl Physiol 1994;77:2853-2862
93. Goldberg SJ, Levy RA, Siassi B, Betten J. The effects of maternal hypoxia and hyperoxia upon the neonatal pulmonary vasculature. Pediatrics 1971;48:528-533
94. Rabinovitch M, Konstam MA, Gamble WJ, et al. Changes in pulmonary blood flow affect vascular response to chronic hypoxia in rats. Circ Res 1983;52:432-441
95. Morin FC III. Ligating the ductus arteriosus before birth causes persistent pulmonary hypertension in the newborn lamb. Pediatr Res 1989;25:245-250
96. Harker LC, Kirkpatrick SK, Friedman WF, Bloor CM. Effects of indomethacin on fetal rat lungs: a possible cause of persistent fetal circulation (PFC). Pediatr Res 1981;15: 147-151
97. Turner GR, Levin DL. Prostaglandin synthesis inhibition in persistent pulmonary hypertension of the newborn. Clin Perinatol 1984;11:581-589
98. Levin DL, Fixler DE, Morriss FC, Tyson J. Morphologic-analysis of the pulmonary vascular bed in infants exposed in utero to prostaglandin synthetase inhibitors. J Pediatr 1978;92:478-483
99. Geggel RL, Reid LM. The structural basis of PPHN. Clin Perinatol 1984;2:525-549
100. Dobyns EL, Wescott JY, Kennaugh JM, et al. Eicosanoids decrease with successful extracorporeal membrane oxygenation therapy in neonatal pulmonary hypertension. Am J Respir Crit Care Med 1994;149:873-880
101. 4 in neonates with hypoxemia and pulmonary hypertension. N Engl J Med 1983;309:77-80
102. Hasegawa N, Oshima M, Kawakami H, Hirano H. Changes in pulmonary tissue of patients with congenital heart disease and Down syndrome: a morphological and histochemical study. Acta Paediatr Jpn 1990;32:60-66
103. Clapp S, Perry BL, Farooki ZQ, et al. Down's syndrome, complete atrioventricular canal, and pulmonary vascular obstructive disease. J Thorac Cardiovasc Surg 1990;100: 115-121
104. Chi TPL, Krovetz LJ. The pulmonary vascular bed in children with down syndrome. J Pediatr 1993;86:533-538
105. Cooney TP, Thurlbeck WM. Pulmonary hypoplasia in down's syndrome. N Engl J Med 1982;307:1170-1173
106. Rich S. Primary pulmonary hypertension. Mt Sinai J Med 1990;57:63-74
107. Houde C, Bohn DJ, Freedom RM, Rabinovitch M. Profile of paediatric patients with pulmonary hypertension judged by responsiveness to vasodilators. Br Heart J 1993;70: 461-468
108. Palevsky HI, Fishman AP. The management of primary pulmonary hypertension. JAMA 1991;265:1014-1020
109. Pascual JM, Prakash UB. Development of pulmonary hypertension after placement of a ventriculoatrial shunt. Mayo Clin Proc 1993;68:1177-1182
110. O'Sullivan J, Chatuverdi R, Bennett MK, Hunter S. Protein S deficiency: early presentation and pulmonary hypertension. Arch Dis Child 1992;67:960-961
111. Rider LG, Clarke WR, Rutledge J. Pulmonary hypertension in a seventeen-year-old boy. J Pediatr 1992;120:149-159
112. Moser KM, Bloor CM. Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. Chest 1993;103:685-692
113. Burchenal JEB, Loscalzo J. Endothelial dysfunction and pulmonary hypertension. Primary Cardiol 1994;20:28-32
114. Barst RJ. Pharmacologically induced pulmonary vasodilatation in children and young adults with primary pulmonary hypertension. Chest 1986;89:497-503
115. Hageman JR, Adams MA, Gardner TH. Persistent pulmonary hypertension of the newborn. Am J Dis Child 1984; 138:592-595
116. Fox WW, Duara S. Persistent pulmonary hypertension in the neonate: diagnosis and management. J Pediatr 1983; 103:505-514
117. Rabinovitch M, Haworth SG, Castaneda AR, et al. Lung biopsy in congenital heart disease: a morphometric approach to pulmonary vascular disease. Circulation 1978; 58:1107-1122
118. Hughes JD, Rubin LJ. Primary pulmonary hypertension. An analysis of 28 cases and a review of the literature. Medicine 1986;65:56-72
119. Burghuber OC, Brunner CH, Schenk P, Weissel M. Pulsed Doppler echocardiography to assess pulmonary artery hypertension in chronic obstructive pulmonary disease. Monaldi Arch Chest Dis 1993;48:121-125
120. Ostrzega E, Maddahi J, Homma H, et al. Quantification of left ventricular myocardial mass in humans by nuclear magnetic resonance imaging. Am Heart J 1980;117:444-452
121. Bouchard A, Higgins CB, Byrd BF, et al. Magnetic resonance imaging in pulmonary arterial hypertension. Am J Cardiol 1985;56:938-942
122. Didier D, Higgins CB. Estimation of pulmonary vascular resistance by MRI in patients with congenital cardiovascular shunt lesions. Am J Roentgenol 1986;146:919-924
123. Caputo GR, Kondo C, Masui T, et al. Right and left lung perfusion: in vitro and in vivo validation with oblique-angle, velocity-encoded cine MR imaging. Radiology 1991;180:693-698
124. Kondo C, Caputo GR, Masui T, et al. Pulmonary hypertension: pulmonary flow quantification and flow profile analysis with velocity-encoded cine MR imaging. Radiology 1992;183:751-758
125. Vogel JHK, Grover RF, Jamieson G, Blount SG. Long-term physiologic observation in patients with ventricular septal defect and increased pulmonary vascular resistance. Adv Cardiol 1974;11:108-122
126. Brammel HL, Vogel JHK, Pryor R, Blount SG. The eisenmenger syndrome: a clinical and physiologic reappraisal. Am J Cardiol 1971;28:679-692
127. Roberts JD Jr, Lang P, Bigatello LM, et al. Inhaled nitric oxide in congenital heart disease. Circulation 1993;87:447-453
128. Bush A, Busst CM, Haworth SG, et al. Correlations of lung morphology, pulmonary vascular resistance, and outcome in children with congenital heart disease. Br Heart J 1988;59:480-485
129. Keane JF, Lock JE. Special studies: exercise, drug studies, and myocardialbiopsy. In: Lock JE, Keane JF, Fellows KE, eds. Diagnostic and interventional catheterization in congenital heart disease. Boston, MA: Martinus Nijhoff, 1987;145-153
130. Heath D, Edwards JE. The pathology of hypertensive pulmonary vascular disease. Circulation 1958;18:533-547
131. Bifano E, Kavey RE, Pergolizzi J, et al. The cardiopulmonary effects of calcium infusion in infants with persistent pulmonary hypertension of the newborn. Pediatr Res 1989;25: 262-265
132. Bush A, Busst CM, Knight WB, Shinebourne EA. Cardiovascular effects of tolazoline and ranitidine. Arch Dis Child 1987;62:241-246
133. Gordon JB, Clément De Cléty S, Chu K. Developmental changes in vascular responses to histamine in normoxic and hypoxic lamb lungs. J Appl Physiol 1991;70:323-330
134. Goetzman BW, Milstein JM. Pulmonary vascular histamine receptors in newborn and young lambs. J Appl Physiol 1980;49:380-385
135. 2 stimulation. Dev Pharmacol Ther 1990;14:180-186
136. Hickey PR, Retzack SM. Acute right ventricular failure after pulmonary hypertensive responses to airway instrumentation: effect of fentanyl dose. Anesthesiology 1993;78: 372-376
137. Anand KJS, Hickey PR. Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl J Med 1992;326:1-56
138. Peake MD, Harabin AL, Brennan AJ, Sylvester JT. Steady-state vascular responses to graded hypoxia in isolated lungs of five species. J Appl Physiol 1981;51:1214-1219
139. 2. Prostaglandins 1981;21:491-503
140. Wetzel RC, Gordon JB, Gregoty TJ, et al. High-frequency ventilation attenuation of hypoxic pulmonary vasoconstriction. Am Rev Respir Dis 1985;132:99-103
141. Lindenberg JA, Goetzman BW, Milstein JM, Bennett SH. Normocarbic hyperventilation fails to induce pulmonary vasodilation. Pediatr Pulmonol 1986;2:194-197
142. Fike CD, Hansen TN. The effect of alkalosis on hypoxia-induced pulmonary vasoconstriction in lungs of newborn rabbits. Pediatr Res 1989;25:383-388
143. Schreiber MD, Heymann MA, Soifer SJ. Increased arterial pH, not decreased PaCO2, attenuates hypoxia-induced pulmonary vasoconstriction in newborn lambs. Pediatr Res 1986;20:113-117
144. Morin FC III. Hyperventilation, alkalosis, prostaglandins, and pulmonary circulation of the newborn. J Appl Physiol 1986;61:2088-2094
145. 2 on pulmonary and systemic hemodynamics after surgery in children with congenital heart disease and pulmonary hypertension. J Pediatr 1988;113:474-479
146. Hammerman C, Yousefzadeh D, Choi JH, Bui KC. Persistent pulmonary hypertension of the newborn. Clin Perinatol 1989;16:137-156
147. Hammerman C, Aramburo MJ. Effects of hyperventilation on prostacyclin formation and on pulmonary vasodilation after group b b-hemolytic streptocci-induced pulmonary hypertension. Pediatr Res 1991;29:282-287
148. Yamaguchi T, O'Brien RF, Hanson WL, et al. Prostacyclin contributes to inhibition of hypoxic pulmonary vasoconstriction by alkalosis. Prostaglandins 1989;38:53-63
149. Fineman JR, Wong J, Soifer SJ. Hyperoxia and alkalosis produce pulmonary vasodilation independent of endothelium-derived nitric oxide in newborn lambs. Pediatr Res 1993;33:341-346
150. Wung JT, James LS, Kilchevsky E, James E. Management of infants with severe respiratory failure and persistence of the fetal circulation, without hyperventilation. Pediatrics 1985;76:488-494
151. Gordon JB, Martinez FR, Keller PA, et al. Differing effects of acute and prolonged alkalosis on hypoxic pulmonary vasoconstriction. Am Rev Respir Dis 1993;148:1651-1656
152. Raffestin B, McMurtry IF. Effects of intracellular pH on hypoxic vasoconstriction in rat lungs. J Appl Physiol 1987;63:2524-2531
153. Berner M, Jaccard C, Oberhänsli I, et al. Hemodynamic effects of amrinone in children after cardiac surgery. Intensive Care Med 1990;16:85-88
154. Robinson BW, Gelband H, Mas MS. Selective pulmonary and systemic vasodilator effects of amrinone in children: new therapeutic implications. J Am Coll Cardiol 1993; 21:1461-1465
155. Stevenson DK, Kasting DS, Darnall RA, et al. Refractory hypoxemia associated with neonatal pulmonary disease: the use and limitations of tolazoline. J Pediatr 1979;95: 595-599
156. Drummond WH, Gregory GA, Heymann MA, Phibbs RA. The independent effects of hyperventilation, tolazoline, and dopamine on infants with persistent pulmonary hypertension. J Pediatr 1981;98:603-611
157. Bush A, Busst CM, Knight WB, Shinebourne EA. Comparison of the haemodynamic effects of epoprostenol (prostacyclin) and tolazoline. Br Heart J 1988;60:141-148
158. Rubin LJ, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Ann Intern Med 1990;112: 485-491
159. 1 treatment of pulmonary hypertension. Am Rev Respir Dis 1987;136: 773-776
160. Bush A, Busst C, Booth K, et al. Does prostacyclin enhance the selective pulmonary vasodilator effect of oxygen in children with congenital heart disease. Circulation 1986; 74:135-144
161. Weir EK, Ruhin LJ, Ayres SM, et al. The acute administration of vasodilators in primary pulmonary hypertension. Am Rev Respir Dis 1989;140:1623-1630
162. Rubin LJ, Groves BM, Reeves JT, et al. Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation 1982;66:334-338
163. 1 and epoprostenol (prostacyclin) in infants after heart surgery. Br Heart J 1991;66:175-178
164. 1 and nitroprusside on pulmonary vascular resistance in children after open-heart surgery. Ann Thorac Surg 1981;32:563-570
165. 2 on perinatal circulation. Am J Physiol 1981;240:H755-H760
166. 2 on pulmonary arterial pressure and oxygenation in newborn infants with persistent pulmonary hypertension. J Pediatr 1988;112:774-777
167. Furchgott RF, Zawadski JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscles in acetylcholine. Nature 1980a;288:373-376
168. Moncada S. The first Robert Furchgott Lecture: from endothelium-dependent relaxation to the L-arginine: NO pathway. Blood Vessels 1990;27:208-217
169. Frostell C, Fratacci MD, Wain JC, et al. Inhaled nitric oxide. Circulation 1991;83:2038-2047
170. Pepke-Zaha J, Higenbottam TW, Dinh-Xuan AT, et al. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 1991;338: 1173-1174
171. Rossaint R, Falke KJ, López FA, et al. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med 1993;328:399-405
172. Zapol WM, Rimar S, Gillis N, et al. Nitric oxide and the lung. Am J Respir Crit Care Med 1994;149:1375-1380
173. Tibballs J. Clinical applications of gaseous nitric oxide. Anesth Intensive Care 1993;21:866-871
174. Kinsella JP, Neish SR, Ivy DD, et al. 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
175. Kinsella JP, Toews WH, Henry D, Abman SH. Selective and sustained pulmonary vasodilation with inhalational nitric oxide therapy in a child with idiopathic pulmonary hypertension. J Pediatr 1993;122:803-806
176. Wessel DL. Inhaled nitric oxide for the treatment of pulmonary hypertension before and after cardiopulmonary bypass. Crit Care Med 1993;21:S344-S345
177. Journois D, Pouard P, Mauriat P, et al. Inhaled nitric oxide as a therapy for pulmonary hypertension after operations for congenital heart defects. J Thorac Cardiovasc Surg 1994;107:1129-1135
178. Wessel DL, Adatia I, Thompson JE, Hickey PK. Delivery and monitoring of inhaled nitric oxide in patients with pulmonary hypertension. Crit Care Med 1994;22:930-938
179. Nagao T, Vanhoutte PM. Endothelium-derived hyperpolarizing factor and endothelium-dependent relaxations. Am J Respir Cell Mol Biol 1993;8:1-6
180. Gordon JB, O'Donnell DC, Tod ML. Sites of inhaled nitric oxide-induced vasodilation during hypoxia and U46619 infusion in isolated lamb lungs. Pediatr Res 1994; 35:392A
181. 2 aerosol versus nitric oxide for selective pulmonary vasodilation in hypoxic pulmonary vasoconstriction. Fur Surg Res 1993; 25:329-340
182. Anderson ME, Burnette TM, Geiser DR, Janjindamai W. Magnesium attenuates pulmonary hypertension due to hypoxia and group B streptococci. J Appl Physiol 1994; 77:751-756
183. 2 in the evaluation and treatment of children with pulmonary hypertension secondary to congenital heart defects. Circulation 1994;90:1287-1293
184. Abman SH, Groothius JR. Pathophysiology and treatment of bronchopulmonary dysplasia. Current issues (review). Pediatr Clin North Am 1994;149:767-775
185. Sime F, Peñaloza D, Ruiz L. Bradycardia, increased cardiac output, and reversal of pulmonary hypertension in altitude natives living at sea level. Br Heart J 1971;33:647-657
186. Kay JM, Suyama KL, Keane PM. Effect of intermittent normoxia on muscularization of pulmonary arterioles induced by chronic hypoxia in rats. Am Rev Respir Dis 1981;123: 454-458
187. Herget J, Suggett AJ, Leach E, Barer GR. Resolution of pulmonary hypertension and other features induced by chronic hypoxia in rats during complete and intermittent normoxia. Thorax 1978;33:468-473
188. Hampl V, Herget J. Perinatal hypoxia increases hypoxic pulmonary vasoconstriction in adult rats recovering from chronic exposure to hypoxia. Am Rev Respir Dis 1990;142: 619-624
189. Davis DA, Russo P. Successful treatment of acute postoperative pulmonary hypertension with nifedipine. Ann Thorac Surg 199253:148-150
190. Brownlee JR, Beekman RH, Rosenthal A. Acute hemodynamic effects of nifedipine in infants with bronchopulmonary dysplasia and pulmonary hypertension. Pediatr Res 1988;24:186-190
191. Webster MWI, Neutze JM, Calder AL. Acute hemodynamic effects of converting enzyme inhibition in children with intracardiac shunts. Pediatr Cardiol 1992;13:129-135
192. Rich S, Brundage BH. High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation 1987;76:135-141
193. Rich S, Kaufman E, Levy PS. Effect of high doses of calcium channel blockers on survival in primary pulmonary hypertension. N Engl J Med 1992;327:76-81
194. Koyama T, Horimoto M. Pulmonary microcirculatory response to localized hypercapnia. J Appl Physiol 1982;53: 1556-1564
195. Jones DK, Higenbottam TW, Wallwork J. Treatment of primary pulmonary hypertension with intravenous epoprostenol (prostacyclin). Br Heart J 1987;57:270-278
196. Rubin LJ, Long WA, et al. Randomized prospective study of prostacyclin in primary pulmonary hypertension. Am Rev Respir Dis 1993:147:A538
197. Kerstein D, Levy PS, Hsu DT, et al. Blade balloon atrial septostomy in patients with severe primary pulmonary hypertension. Circulation 1995;91:2028-2035
198. Reitz BA, Wallwork JL, Hunt SA, et al. Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease. N Engl J Med 1982;306:557-564
199. Pasque MK, Kaiser LR, Dresler CM, et al. Single lung transplantation for pulmonary hypertension. Technical aspects and immediate hemodynamic results. J Thorac Cardiovasc Surg 1992;103:475-481