Abstract
Because minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing bronchopulmonary dysplasia, using stable isotopes, radioactive isotopes, and direct pool size measurements. Eight ventilated premature baboons received 2H-DPPC (dipalmitoyl phosphatidylcholine) on d 5 of life, and radioactive 14C-DPPC with a treatment dose of surfactant on d 8. After 14 d, lung pool sizes of saturated phosphatidylcholine were measured. Half-life of 2H-DPPC (d 5) in tracheal aspirates was 28 ± 4 h (mean ± SEM). Half-life of radioactive DPPC (d 8) was 35 ± 4 h. Saturated phosphatidylcholine pool size measured with stable isotopes on d 5 was 129 ± 14 μmol/kg, and 123 ± 11 μmol/kg on d 14 at autopsy. Half-lives were comparable to those obtained at d 0 and d 6 in our previous baboon studies. We conclude that surfactant metabolism does not change during the early development of bronchopulmonary dysplasia, more specifically, the metabolism of exogenous surfactant on d 8 is similar to that on the day of birth. Surfactant pool size is low at birth, increases after surfactant therapy, and is kept constant during the first 2 wk of life by endogenous surfactant synthesis. Measurements with stable isotopes are comparable to measurements with radioactive tracers and measurements at autopsy.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- RDS:
-
respiratory distress syndrome
- BPD:
-
bronchopulmonary dysplasia
- GA:
-
gestational age
- DPPC:
-
dipalmitoyl phosphatidylcholine
- Sat PC:
-
saturated phosphatidylcholine
- PG:
-
phosphatidylglycerol
- Sp:
-
sphingomyelin
References
Jobe AH 1993 Pulmonary surfactant therapy. N Engl J Med 328: 861–868
Jobe AH 1988 The role of surfactant in neonatal adaptation. Semin Perinatol 12: 113–123
Jobe AH 1988 Metabolism of endogenous surfactant exogenous surfactants for replacement therapy. Semin Perinatol 12: 231–244
Jobe AH, Ikegami M 1998 Surfactant acute lung injury. Proc Assoc Am Physicians 110: 489–495
Bland RD, Coalson JJ 2000 Chronic Lung Disease in Early Infancy. Marcel Dekker, New York
Bancalari E, del Moral T 2001 Bronchopulmonary dysplasia surfactant. Biol Neonate 80( suppl 1): 7–13
Clement A, Masliah J, Housset B, Just J, Garcia J, Grimfeld A, Tournier G 1987 Decreased phosphatidyl choline content in bronchoalveolar lavage fluids of children with bronchopulmonary dysplasia: a preliminary investigation. Pediatr Pulmonol 3: 67–70
Hallman M, Merritt TA, Akino T, Bry K 1991 Surfactant protein a, phosphatidylcholine, surfactant inhibitors in epithelial lining fluid. Correlation with surface activity, severity of respiratory distress syndrome, outcome in small premature infants. Am Rev Respir Dis 144: 1376–1384
Pandit PB, Dunn MS, Kelly EN, Perlman M 1995 Surfactant replacement in neonates with early chronic lung disease. Pediatrics 95: 851–854
Coalson JJ, Seidner S, deLemos RA 2000 Animal models of chronic lung injury. In: Bland RD, Coalson JJ (eds) Chronic Lung Disease in Early Infancy. Marcel Dekker, New York, pp 927–956
Seidner SR, Jobe AH, Coalson JJ, Ikegami M 1998 Abnormal surfactant metabolism function in preterm ventilated baboons. Am J Respir Crit Care Med 158: 1982–1989
Awasthi S, Coalson JJ, Crouch E, Yang F, King RJ 1999 Surfactant proteins a d in premature baboons with chronic lung injury (bronchopulmonary dysplasia). Evidence for an inhibition of secretion. Am J Respir Crit Care Med 160: 942–949
Bunt JE, Zimmermann LJI, Wattimena JLD, Beek v RH, Sauer PJJ, Carnielli VP 1998 Endogenous surfactant turnover in preterm infants measured with stable isotopes. Am J Respir Crit Care Med 157: 810–814
Torresin M, Zimmermann LJ, Cogo PE, Cavicchioli P, Badon T, Giordano G, Zacchello F, Sauer PJ, Carnielli VP 2000 Exogenous surfactant kinetics in infant respiratory distress syndrome: a novel method with stable isotopes. Am J Respir Crit Care Med 161: 1584–1589
Adams FH, Fujiwara T, Emmanouilides GC, Raiha N 1970 Lung phospholipids of human fetuses infants with without hyaline membrane disease. J Pediatr 77: 833–841
Bunt JE, Carnielli VP, Seidner SR, Ikegami M, Darcos Wattimena JL, Sauer PJ, Jobe AH, Zimmermann LJ 1999 Metabolism of endogenous surfactant in premature baboons effect of prenatal corticosteroids. Am J Respir Crit Care Med 160: 1481–1485
IJsselstijn H, Zimmermann LJI, Bunt JEH, de Jongste JC, Tibboel D 1998 Prospective evaluation of surfactant composition in bronchoalveolar lavage fluid of infants with congenital diaphragmatic hernia of age-matched controls. Crit Care Med 26: 573–580
Wolfe RR 1992 Radioactive and Stable Isotope Tracers in Biomedicine. Principles and Practice of Kinetic Analysis. Wiley-Liss, New York
Northway WH, Rosan RC, Porter DY 1967 Pulmonary disease following respiratory therapy of hyaline-membrane disease: bronchopulmonary dysplasia. N Engl J Med 276: 357–368
Jobe AJ 1999 The new BPD: An arrest of lung development. Pediatr Res 46: 641–643
Coalson JJ, Winter VT, Siler-Khodr T, Yoder BA 1999 Neonatal chronic lung disease in extremely immature baboons. Am J Respir Crit Care Med 160: 1333–1346
Seidner SR, Jobe AH, Ikegami M 2000 Surfactant metabolism following late surfactant treatment doses during BPD development in preterm baboons. Pediatr Res 47: 376A( abstr)
Ohashi T, Pinkerton K, Ikegami M, Jobe AH 1994 Changes in alveolar surface area, surfactant protein a, saturated phosphatidylcholine with postnatal rat lung growth. Pediatr Res 35: 685–689
Jackson JC, Palmer S, Truog WE, Standaert TA, Murphy JH, Hodson WA 1986 Surfactant quantity composition during recovery from hyaline membrane disease. Pediatr Res 20: 1243–1247
Michna J, Jobe AH, Ikegami M 1999 Positive end-expiratory pressure preserves surfactant function in preterm lambs. Am J Respir Crit Care Med 160: 634–639
Jobe AH, Newnham JP, Willet KE, Moss TJ, Gore Ervin M, Padbury JF, Sly P, Ikegami M 2000 Endotoxin-induced lung maturation in preterm lambs is not mediated by cortisol. Am J Respir Crit Care Med 162: 1656–1661
Hallman M, Merritt TA, Pohjavuori M, Gluck L 1986 Effect of surfactant substitution on lung effluent phospholipids in respiratory distress syndrome: evaluation of surfactant phospholipid turnover, pool size, the relationship to severity of respiratory failure. Pediatr Res 20: 1228–1235
Griese M, Dietrich P, Reinhardt D 1995 Pharmacokinetics of bovine surfactant in neonatal respiratory distress syndrome. Am J Respir Crit Care Med 152: 1050–1054
Ikegami M, Jobe AH, Yamada T, Priestly A, Ruffini L, Rider E, Seidner SR 1989 Surfactant metabolism in surfactant-treated preterm ventilated lambs. J Appl Physiol 67: 429–437
Glatz T, Ikegami M, Jobe AH 1982 Metabolism of exogenously administered natural surfactant in the newborn lamb. Pediatr Res 16: 711–715
Bunt JE, Carnielli VP, Janssen DJ, Wattimena JL, Hop WC, Sauer PJ, Zimmermann LJ 2000 Treatment with exogenous surfactant stimulates endogenous surfactant synthesis in premature infants with respiratory distress syndrome. Crit Care Med 28: 3383–3388
Kramer BW, Ikegami M, Jobe AH 2000 Surfactant phospholipid catabolic rate is pool size dependent in mice. Am J Physiol Lung Cell Mol Physiol 279: L842–L848
Acknowledgements
The authors thank Wim van den Berg (Internal Medicine II, Erasmus University Rotterdam, The Netherlands), Jan Erik Bunt (Department of Pediatrics, Sophia Children's Hospital Rotterdam, The Netherlands) for excellent support and technical advice, Esther Wit and Lars de Zeeuw (medical students, Erasmus University, Rotterdam, The Netherlands) for technical assistance, and the BPD Resource Center at the Southwest Foundation for Biomedical Research.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by grants from the Sophia Foundation for Medical Research (SSWO 245), Rotterdam, The Netherlands, and the National Institute of Child Health, HL 52635 (The Southwest Foundation for Biomedical Research BPD Resource Center).
Rights and permissions
About this article
Cite this article
Janssen, D., Carnielli, V., Cogo, P. et al. Surfactant Phosphatidylcholine Half-life and Pool Size Measurements in Premature Baboons Developing Bronchopulmonary Dysplasia. Pediatr Res 52, 724–729 (2002). https://doi.org/10.1203/00006450-200211000-00019
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-200211000-00019