What Happens to Treatment Doses of Surfactant?

  • A. Jobe
  • A. Pettenazzo
  • S. Seidner
  • M. Ikegami
Conference paper

Abstract

To start this discussion of what happens to treatment doses of surfactant, perhaps the conclusion should be stated first: we know very little about the fate of exogenously administered surfactants. Almost all the data available are from animal models and there is no quantitative information from the human. To further complicate the issue, multiple variables relating to the surfactant tested and the animal or human receiving the surfactant probably change overall clearance measurements. The pathways responsible for clearance also may change under different conditions. Some of the variables that have some experimental foundation are listed in Table 1. Each investigator has used different surfactants at different doses that have been resuspended in different water based vehicles for administration [10, 43–45, 53]. The aggregate sizes and lipid structures will differ based on the calcium, surfactant protein, and suspension techniques selected [39]. Total phosphatidylcholine or saturated phosphatidylcholine have been studied almost exclusively, and other components of surfactant may have different fates [53]. It is clear that catabolic rates change with lung development, as do macrophage numbers and the distributions of other cell types in the lungs. Surfactant treatments will be used clinically only for lung immaturity or in lung injury. The severity of lung immaturity probably influences surfactant clearance rates [26]. In the adult lung, the type of injury will no doubt affect the fate of exogenous surfactants [3, 4, 37]. A primarily epithelial injury with type II cell damage will change surfactant catabolism differently than will an endothelial injury with complicating alveolar edema. Mechanical ventilation in the developing or adult lung may also change surfactant clearance kinetics [11]. Also the health of the lung in terms of basic metabolic and healing processes will be influenced by nutritional status [5]. The results to be summarized in this review relate primarily to healthy lungs in animals as very little information is available that is directly applicable to the injured lung.

Keywords

Lamellar Body Adult Rabbit Natural Surfactant Exogenous Surfactant Surfactant Treatment 
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References

  1. 1.
    Baritussio A, Carraro R, Bellina L, Rossi A, Bruni R, Pettenazzo A, Enzi G (1985) Turnover of phospholipids isolated from fractions of lung lavage fluid. J Appl Physiol 59: 1055–1060PubMedGoogle Scholar
  2. 2.
    Baritussio A, Magoon MW, Goerke J, Clements JA (1981) Precursor-product relationship between rabbit type II cell lamellar bodies and alveolar surface active material. Surfactant turnover time. Biochim Biophys Acta 666: 382–393PubMedGoogle Scholar
  3. 3.
    Berggren P, Lachmann B, Curstedt T, Grossmann G, Robertson B (1986) Gas exchange and lung morphology after surfactant replacement in experimental adult respiratory distress syndrome induced by repeated lung lavage. Acta Anaesthesiol Scand 30: 321–328PubMedCrossRefGoogle Scholar
  4. 4.
    Berry D, Ikegami M, Jobe A (1986) Respiratory distress and surfactant inhibition following vagotomy in rabbits. J Appl Physiol 61: 1741–1748PubMedGoogle Scholar
  5. 5.
    Brown LAS, Bliss AS, Longmore WJ (1984) Effect of nutritional status on the lung surfactant system: Food deprivation and caloric restriction. Exp Lung Res 6: 133–147PubMedCrossRefGoogle Scholar
  6. 6.
    Chander A, Reicherter J, Fisher AB (1987) Degradation of dipalmitoyl phosphatidylcholine by isolated rat granular pneumocytes and reutilization for surfactant synthesis. J Clin Invest 79: 1133–1138PubMedCrossRefGoogle Scholar
  7. 7.
    Chevalier G, Collet AJ (1972) In vivo incorporation of choline 3H, leucine-3H and galactose-3H in alveolar type II pneumocytes in relation to surfactant synthesis. A quantitative radioautographic study in mouse by electron microscopy. Anat Rec 174: 289–310PubMedCrossRefGoogle Scholar
  8. 8.
    Davis PA, Gunther RA, Cross CE (1987) Clearance of instilled surfactant lipid from the lungs of unanesthetized sheep: lipids are differentially transported by nonlymphatic pathways. J Lab Clin Med 109: 191–200PubMedGoogle Scholar
  9. 9.
    Desai R, Tetley TD, Curtis CG, Powell GM, Richards RJ (1978) Studies on the fate of pulmonary surfactant in the lung. Biochem J 176: 455–462PubMedGoogle Scholar
  10. 10.
    Egan EA, Notter RH, Kwong MS, Shapiro DL (1983) Natural and artificial lung surfactant replacement therapy in premature lambs. J Appl Physiol 55: 875–883PubMedGoogle Scholar
  11. 11.
    Ennema JJ, Reijngoud D-J, Wildevuur CHRH, Egberts J (1984) Effects of artificial ventilation on surfactant phospholipid metabolism in rabbits. Respir Physiol 58: 15–28PubMedCrossRefGoogle Scholar
  12. 12.
    Fisher AB, Dodia C, Chander A (1987) Degradation and reutilization of alveolar phosphatidylcholine by rat lungs. J Appl Physiol 62: 2295–2299PubMedCrossRefGoogle Scholar
  13. 13.
    Geiger K, Gallagher ML, Hedley-Whyte J (1975) Cellular distribution and clearance of aerosolized dipalmitoyl lecithin. J Appl Physiol 39: 759–766PubMedGoogle Scholar
  14. 14.
    Glatz T, Ikegami M, Jobe A (1982) Metabolism of exogenously administered natural surfactant in the newborn lamb. Pediatr Res 16: 711–715PubMedCrossRefGoogle Scholar
  15. 15.
    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, and the relationship to severity of respiratory failure. Pediatr Res 20: 1228–1235PubMedCrossRefGoogle Scholar
  16. 16.
    Hallman M, Epstein BL, Gluck L (1981) Analysis of labeling and clearance of lung surfactant phospholipids in rabbit. Evidence of bi-directional surfactant flux between lamellar bodies and alveolar lavage. J Clin Invest 68: 742–751PubMedCrossRefGoogle Scholar
  17. 17.
    Heath MF, Jacobson W (1984) Developmental changes in enzyme activities in fetal and neonatal rabbit lung. Cytidylyltransferase, cholinephosphotransferase, phospholipases At and A2, ß-galactosidase, and 3-glucuronidase. Pediatr Res 18: 395–401PubMedCrossRefGoogle Scholar
  18. 18.
    Ikegami M, Jobe A, Glatz T (1981) Surface activity following natural surfactant treatment in premature lambs. J Appl Physiol 51: 306–312PubMedGoogle Scholar
  19. 19.
    Ikegami M, Jobe A, Nathanielsz PW (1981) The labeling of pulmonary surfactant phosphatidylcholine in newborn and adult sheep. Exp Lung Res 2: 197–206PubMedCrossRefGoogle Scholar
  20. 20.
    Jackson SC, Palmer S, Standaert TA, Murphy J, Truog WE, Woodrum DE, Hodson WA (1984) Developmental changes of surface active material in newborn nonhuman primates. Am Rev Respir Dis 129: A204Google Scholar
  21. 21.
    Jacobs H, Jobe A, Ikegami M, Conaway D (1983) The significance of reutilization of surfactant phosphatidylcholine. J Biol Chem 258: 4159–4165PubMedGoogle Scholar
  22. 22.
    Jacobs HC, Ikegami M, Jobe AH, Berry DD, Jones S (1985) Reutilization of surfactant phosphatidylcholine in adult rabbits. Biochim Biophys Acta 837: 77–84PubMedGoogle Scholar
  23. 23.
    Jacobs H, Jobe A, Ikegami M, Jones S (1982) Surfactant phosphatidylcholine source, fluxes, and turnover times in 3-day-old, 10-day-old, and adult rabbits. J Biol Chem 257: 1805–1810PubMedGoogle Scholar
  24. 24.
    Jacobs H, Jobe A, Ikegami M, Jones S (1985) Accumulation of alveolar surfactant following delivery and ventilation of premature lambs. Exp Lung Res 8: 125–140PubMedCrossRefGoogle Scholar
  25. 25.
    Jacobs H, Jobe A, Ikegami M, Miller D, Jones S (1984) Reutilization of phosphatidylcholine analogues by the pulmonary surfactant system. The lack of specificity. Biochim Biophys Acta 793: 300–309Google Scholar
  26. 26.
    Jobe A (1985) Difference in surfactant between the developing and adult lung. J Jpn Med Soc Biol Interface 16: 9–18Google Scholar
  27. 27.
    Jobe A, Gluck L (1979) The labeling of lung phosphatidylcholine in premature rabbits. Pediatr Res 13: 635–640PubMedCrossRefGoogle Scholar
  28. 28.
    Jobe A, Ikegami M (1984) The prematurely delivered lamb as a model for studies of neonatal adaptation. In: Nathanielsz PW (ed) Animal models in fetal medicine. Perinatology, Ithaca NY, pp 1–30Google Scholar
  29. 29.
    Jobe A, Ikegami M, Jacobs H (1981) Changes in the amount of lung and airway phosphatidylcholine in 0.5–12.5-day-old rabbits. Biochim Biophys Acta 664: 182–187PubMedGoogle Scholar
  30. 30.
    Jobe A, Ikegami M, Jacobs H, Jones S (1983) Surfactant pool sizes and severity of RDS in prematurely delivered lambs. Am Rev Respir Dis 127: 751–755PubMedGoogle Scholar
  31. 31.
    Jobe A, Ikegami M, Sarton-Miller I, Barajas L (1980) Surfactant metabolism of newborn lamb lungs in vivo. J Appl Physiol 49: 1091–1098PubMedGoogle Scholar
  32. 32.
    Jobe A, Ikegami M, Sarton-Miller I, Jones S, Yu G (1981) Characterization of phospholipids and localization of some phospholipid synthetic and subcellular marker enzymes in subcellular fractions from rabbit lung. Biochim Biophys Acta 666: 47–57PubMedGoogle Scholar
  33. 33.
    Jobe AH, Jacobs HC (1984) Catabolism of pulmonary surfactant. In: Robertson B, Van Golde LMG, Batenburg JJ (eds) Pulmonary surfactant. Elsevier Science, Amsterdam, pp 271–293Google Scholar
  34. 34.
    Jobe A, Kirkpatrick E, Gluck L (1978) Lecithin appearance and apparent biologic half-life in term newborn rabbit lung. Pediatr Res 12: 669–675PubMedCrossRefGoogle Scholar
  35. 34.
    Jobe A, Kirkpatrick E, Gluck L (1978) Lecithin appearance and apparent biologic half-life in term newborn rabbit lung. Pediatr Res 12: 669–675PubMedCrossRefGoogle Scholar
  36. 36.
    Magoon MW, Wright JR, Baritussio A, Williams MC, Goerke J, Benson BJ, Hamilton RL, Clements JA (1983) Subfractionation of lung surfactant. Implications for metabolism and surface activity. Biochim Biophys Acta 750: 18–31PubMedGoogle Scholar
  37. 37.
    Matalon S, Holm BA, Notter RH (1987) Mitigation of pulmonary hyperoxic injury by administration of exogenous surfactant. J Appl Physiol 62: 756–761PubMedGoogle Scholar
  38. 38.
    Nichols BA (1976) Normal rabbit alveolar macrophages. I. The phagocytosis of tubular myelin. J Exp Med 144: 906–919PubMedCrossRefGoogle Scholar
  39. 39.
    Notter RH, Egan EA, Kwong MS, Holm BA, Shapiro DL (1985) Lung surfactant replacement in premature lambs with extracted lipids from bovine lung lavage: effects of dose, dispersion technique, and gestational age. Pediatr Res 19: 569–577PubMedCrossRefGoogle Scholar
  40. 40.
    Oguchi K, Ikegami M, Jacobs J, Jobe A (1985) Clearance of large amounts of natural surfactant and DPPC from lungs of 3-day-old rabbits following tracheal injection. Exp Lung Res 9: 221–235PubMedCrossRefGoogle Scholar
  41. 41.
    Oyarzun MJ, Clements JA, Baritussio A (1980) Ventilation enhances pulmonary alveolar clearance of radioactive dipalmitoylphosphatidylcholine in liposomes. Am Rev Respir Dis 121: 709–721PubMedGoogle Scholar
  42. 42.
    Paul GW, Hassett RJ, Reiss OK (1977) Formation of lung surfactant films from intact lamellar bodies. Proc Natl Acad Sci USA 74: 3617–3620PubMedCrossRefGoogle Scholar
  43. 43.
    Pettenazzo A, Ikegami M, Seidner S, Jobe A (1988) Clearance of surfactant phosphatidylcholine from adult rabbit lungs. J Appl Physiol 64: 120–127PubMedGoogle Scholar
  44. 44.
    Pettenazzo A, Jobe A, Ikegami M, Seidner S (1988) Clearance of treatment doses of surfactant. Effect of lipid extraction and aggregate sizes. Biol Neonate 53: 23–31PubMedCrossRefGoogle Scholar
  45. 45.
    Pettenazzo A, Oguchi K, Seidner S, Ikegami M, Berry D, Jobe A (1986) Clearance of natural surfactant phosphatidylcholine from 3-day-old rabbit lungs: effects of dose and species. Pediatr Res 20: 1139–1142PubMedCrossRefGoogle Scholar
  46. 46.
    Seidner SR, Ikegami M, Pettenazzo A, Ruffini L, Jobe A (1987) Clearance of surfactant phosphatidylcholine from the lungs of preterm ventilated rabbits. Pediatr Res 21: 465AGoogle Scholar
  47. 47.
    Solimano A, Bryan C, Jobe A, Ikegami M, Jacobs H (1985) Effects of high-frequency and conventional ventilation on the premature lamb lung. J Appl Physiol 59: 1571–1577PubMedGoogle Scholar
  48. 48.
    Tarpey MM, O’Brodovich HM, Young SL (1983) Role of lymphatics in removal of sheep lung surfactant lipid. J Appl Physiol 54: 984–988PubMedGoogle Scholar
  49. 49.
    Wilkinson A, Jenkins PA, Jeffrey JA (1985) Two controlled trials of dry artificial surfactant: early effects and later outcome in babies with surfactant deficiency. Lancet: 287–291Google Scholar
  50. 50.
    Williams MC (1984) Uptake of lectins by pulmonary alveolar type II cells: subsequent deposition into lamellar bodies. Proc Natl Acad Sci USA 81: 6383–6387PubMedCrossRefGoogle Scholar
  51. 51.
    Williams MC (1987) Vesicles within vesicles: what role do multivesicular bodies play in alveolar type II cells. Am Rev Respir Dis 135: 744–746PubMedGoogle Scholar
  52. 52.
    Wright JR, Benson BJ, Williams MC, Goerke J, Clements JA (1984) Protein composition of rabbit alveolar surfactant subfractions. Biochim Biophys Acta 791: 320–332PubMedCrossRefGoogle Scholar
  53. 53.
    Wright JR, Wager RE, Hamilton RL, Huang M, Clements JA (1986) Uptake of lung surfactant subfractions into lamellar bodies of adult rabbit lungs. J Appl Physiol 60: 817–825PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • A. Jobe
  • A. Pettenazzo
  • S. Seidner
  • M. Ikegami

There are no affiliations available

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