Abstract
Laboratory evidence has recently confirmed clinical reports suggesting that the surfactant system is abnormal in congenital diaphragmatic hernia (CDH). Autopsy series show that, although both lungs are affected by the maldevelopment, the ipsilateral lung is more severely affected. The aim of this study was to examine the surfactant status in each lung in a lamb model of CDH. The lamb CDH model was created on the left side at 80 d of gestation and delivered near term. Subsequently, the lungs were removed and separated from each other. Bronchoalveolar lavage and type II pneumocyte isolations were performed on each side separately. Lavage analyses showed decreased phospholipid (0.12 versus 0.42 mg/g), per cent phosphatidylcholine(51% versus 79%) surfactant-associated protein A (0.20versus 2.68 mg/g), and surfactant-associated protein-B (0.35versus 2.21 mg/g) in CDH lungs compared with control lungs. However, no differences were seen between the ipsilateral and contralateral lungs of either CDH or control groups. This was in contrast to the phosphatidylcholine biosynthetic abilities of type II cells isolated from CDH lungs, which were not only lower than those from control lungs (0.15 versus 0.40 nmol/106 cells/h), but were also significantly worse in the ipsilateral CDH lung compared with the contralateral CDH lung (0.10 versus 0.20 nmol/106 cells/h). Further studies utilizing radiolabeled exogenous surfactant injected in the lower contralateral lung indicate that discrepancies between the presence of type II cell function differences between lungs, and the lack of biochemical differences between the two lungs in CDH, may be due to in utero mixing of lung fluid.
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Abbreviations
- CDH:
-
congenital diaphragmatic hernia
- BAL:
-
bronchoalveolar lavage
- DPPC:
-
dipalmitoylphosphatidylcholine
- PC:
-
phosphatidylcholine
- MEM:
-
minimal essential medium
- SP:
-
surfactant-associated protein
References
Adzick NS, Harrison MR, Cutwater KM, Davies P, Glick PL, De Lorimier AA, Reid L 1985 Correction of congenital diaphragmatic hernia in utero. IV. An early gestational fetal lamb model for pulmonary vascular morphometric analysis. J Pediatr Surg 20: 673–680
Hislop A, Reid L 1976 Persistent hypoplasia of the lung after repair of congenital diaphragmatic hernia. Thorax 31: 450–455
Levin DL 1978 Morphologic analysis of the pulmonary vascular bed in congenital left-sided diaphragmatic hernia. J Pediatr 92: 805–809
Adzick NS, Harrison MR, Glick PL, Nakamaya DK, Manning FA, De Lorimier AA 1985 Diaphragmatic hernia in the fetus: prenatal diagnosis and outcome in 94 cases. J Pediatr Surg 20: 357–361
Pringle KC, Turner JW, Schofield JC, Soper JT 1984 Creation and repair of diaphragmatic hernia: lung development and morphology. J Pediatr Surg 19: 131–140
Blackburn WR, Logsdon P, Alexander JA 1977 Congenital diaphragmatic hernia: studies of lung composition and structure. Am Rev Respir Dis 115S: 275
Wigglesworth JS, Desia R, Guerrini P 1981 Fetal lung hypoplasia: biochemical and structural variations and their possible significance. Arch Dis Child 56: 606–615
Glick PL, Stannard VA, Leach CL, Rossman J, Hosada Y, Cooney DR, Allen JA, Holm BA 1992 Pathophysiology of congenital diaphragmatic hernia. II. The fetal lamb model is surfactant deficient. J Pediatr Surg 27: 382–388
Suen HC, Catlin EA, Ryan DP, Wain JC, Donahoe PK 1993 Biochemical immaturity of lungs in congenital diaphragmatic hernia. J Pediatr Surg 28: 471–477
Finkelstein JN, Shapiro DL 1982 Isolation of type II alveolar epithelial cells using low protease concentrations. Lung 160: 85–98
Bos AP, Tibbeol D, Hazebroek FW, Molnaar JC, Lachmann B, Gommers D 1991 Surfactant replacement therapy in high-risk congenital diaphragmatic hernia. Lancet 338: 1279
Glick PL, Leach CL, Egan EA, Morin FC, Robinson LK, Brody A, Lele AS, McDonnell M, Holm BA, Besner GE, Rodgers BT, Msall M, Karp MP, Allen JE, Jewett TC, Cooney DR 1992 Pathophysiology of congenital diaphragmatic hernia. III. Exogenous surfactant therapy for the high-risk neonate with CDH. J Pediatr Surg 27: 866–869
Wilcox DT, Glick PL, Rossman J, Morin FC, Holm BA 1994 Pathophysiology of congenital diaphragmatic hernia. V. Exogenous surfactant therapy improves gas exchange and pulmonary mechanics in the lamb congenital diaphragmatic hernia model. J Pediatr 124: 289–293
Bligh EG, Dyer WJ 1959 A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37: 911–917
Chen PS, Toribara TY, Huber W 1956 Microdetermination of phosphorous. Anal Chem 28: 1756–1758
Touchstone JC, Chen JC, Beaver KM 1980 Improved separation of phospholipids in thin layer chromatography. Lipids 15: 61–62
Pruyhuber GS, Hull WM, Fink I, McMahoan MJ, Whitsett JA 1991 Ontogeny of surfactant proteins A and B in human amniotic fluid as indices of fetal lung maturation. Pediatr Res 30: 597–605
Lowry DH, Rosebrough NJ, Farr AL, Randall RJ 1951 Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Laemmli UK 1970 Cleavage of structural proteins during assembly of the head of bacteriophage T4. Nature 227: 680–685
Matthews DE, V Farewell (eds) 1985 Using and Understanding Medical Statistics. S Kager, Basel, Switzerland
Harrison MR, Jester JA, Ross NA 1980 Correction of congenital diaphragmatic hernia in utero. I. The model: intrathoracic balloon procedures fatal pulmonary hypoplasia. Surgery 88: 174–181
Notter RH, Finkelstein JN 1984 Pulmonary surfactant: an interdisciplinary approach. J Appl Physiol 57: 1613–1624
Hawgood S, Schiffer K 1991 Structures and properties of the surfactant associated proteins. Annu Rev Physiol 53: 375–394
Holm BA, Matalon S 1989 Role of pulmonary surfactant in the development and treatment of adult respiratory distress syndrome. Anesth Analg 69: 805–818
Wilcox DT, Glick PL, Karamanoukian H, Holm BA 1994 Pathophysiology of congenital diaphragmatic hernia. IX. Correlation of surfactant maturation with fetal cortisol and triiodothyronine concentration. J Pediatr Surg 29: 825–827
Egan EA, Dillon WP, Zorn W 1984 Fetal lung liquid absorption and alveolar epithelial solute permeability in surfactant deficient, breathing fetal lambs. Pediatr Res 18: 566–570
Zimmerman LJ, Iisselstijn H, Scheffers EC, Sauer PJJ, Batenburg JJ, Tibboil D 1994 Decreased activity of phosphocholine cytidyltransferase in type II pneumocytes from rats with congenital diaphragmatic hernia. Pediatr Res 35: 359
Acknowledgements
The authors thank Jon Rossman, Terri Jones, Cindy Maloney, and June Sokolowski for their technical assistance. We also thank Drs. Jeffery Whitsett and William Hull for surfactant protein analyses.
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Supported in part by the Women and Children's Health and Research Foundation, American Lung Association, National Institutes of Health Grants HL 36543 and HL 45170, and U.S. Surgical Corp., Norwalk, CT.
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Wilcox, D., Glick, P., Karamanoukian, H. et al. Contributions by Individual Lungs to the Surfactant Status in Congenital Diaphragmatic Hernia. Pediatr Res 41, 686–691 (1997). https://doi.org/10.1203/00006450-199705000-00014
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DOI: https://doi.org/10.1203/00006450-199705000-00014
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