Abstract
Premature rabbit neonates (gestational age 27 days) were treated at birth with natural surfactant purified from chloroform extracts of porcine lung lipids either by acetone precipitation (Surfactant CK, n=10) or liquid gel chromatography (Curosurf, n=22). Another group of animals received artificial surfactant “reconstituted” from isolated low molecular weight (≤15 K) apoproteins and synthetic dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) (Aposurf, n=10). The phospholipid concentrations of the preparations were adjusted to provide the same individual dose of DPPC for each group of treated animals (3 or 4 mg). In comparison with untreated controls from the same litters, there was a 4–7-fold enhancement of lungthorax compliance in all groups of surfactant-treated animals during a 3-h period of artificial ventilation. The average initial (20 min) compliance value was lower in the Aposurf-treated group than in animals receiving natural surfactant preparations, but the difference between the groups gradually diminished and was no longer statistically significant during the 2nd and 3rd h of artificial ventilation. Judged from the fall in tidal volume during ventilation with a short expiration phase (0.17 instead of 0.75s), the apoprotein-based artificial surfactant was also less effective in stabilizing the lungs. A similar conclusion could be drawn from data on alveolar expansion in histological sections, evaluated by automated image analysis. Alveolar volume density was improved only moderately in the Aposurf-treated group (0.24 vs. 0.14; P=0.05), whereas the expected, prominent increase in this parameter was observed in both groups of natural surfactant-treated animals (0.48–0.62 vs. 0.14; P<0.001). We conclude that a physiologically active artificial surfactant can be prepared from the smaller (≤15 K) apoproteins, DPPC and DPPG; the in vivo effects of this preparation were clearly beneficial, yet inferior to those obtained with the same dose of natural surfactant.
Similar content being viewed by others
Abbreviations
- DPPC:
-
dipalmitoylphosphatidylcholine
- DPPG:
-
dipalmitoylphosphatidylglycerol
- RDS:
-
respiratory distress syndrome
- Vv :
-
volume density
- CV:
-
coefficient of variation
- dVT :
-
tidal volume reduction
- K:
-
kilodalton(s)
References
Bangham AD, Morley CJ, Phillips MC (1979) The physical properties of an effective lung surfactant. Biochim Biophys Acta 573: 552–556
Clements JA (1977) Functions of the alveolar lining. Am Rev Respir Dis 115: 67–71
Enhörning G, Grossmann G, Robertson B (1973) Tracheal deposition of surfactant before the first breath. Am Rev Respir Dis 107: 921–927
Grossmann G, Nilsson R, Robertson B (1986) Scanning electron microscopy of epithelial lesions induced by artificial ventilation of the immature neonatal lung: the prophylactic effect of surfactant replacement. Eur J Pediatr 145: 361–367
Ikegami M, Jobe A, Jacobs H, Lam R (1984) A protein from the airways of premature lambs that inhibits surfactant function. J Appl Physiol 57: 1134–1142
Ikegami M, Jobe A, Berry D (1986) A protein that inhibits surfactant in respiratory distress syndrome. Biol Neonate 50: 121–129
Ikegami M, Berry D, ElKady T, Pettenazzo A, Seidner S, Jobe A (1987) Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits. J Clin Invest 79: 1371–1378
Jacobs H, Jobe A, Ikegami M, Conaway D (1983) The significancer of reutilization of surfactant phosphatidylcholine. J Biol Chem 258: 4156–4165
Jacobs HC, Ikegami M, Jobe AH, Berry D, Jones S (1985) Reutilization of surfactant phosphatidylcholine in adult rabbits. Biochim Biophys Acta 837: 77–84
Kobayashi T, Grossmann G, Robertson B, Ueda T (1984) Effects of artificial and natural surfactant supplementation in immature newborn rabbits. J Jpn Med Soc Biol Interface 15: 125–131
Lachmann B, Grossmann G, Freyse J, Robertson B (1981) Lungthorax compliance in the artificially ventilated premature rabbit neonate in relation to variations in inspiration: expiration ratio. Pediatr Res 15: 833–838
Lachmann B, Grossmann G, Nilsson R, Robertson B (1981) Effect of supplementary surfactant on in vivo lung mechanics in the preterm rabbit neonate. Eur J Pediatr 136: 173–179
Lachmann B, Berggren P, Curstedt T, Grossmann G, Robertson B (1982) Combined effects of surfactant substitution and prolongation of inspiration phase in artificially ventilated premature newborn rabbits. Pediatr Res 16: 921–927
Nilsson R (1982) The artificially ventilated preterm rabbit neonate as experimental model of hyaline membrane disease. Acta Anaesthesiol Scand 26: 89–103
Nilsson R, Grossmann G, Robertson B (1978) Lung surfactant and the pathogenesis of neonatal bronchiolar lesions induced by artificial ventilation. Pediatr Res 12: 249–255
Nilsson R, Grossmann G, Robertson B (1980) Bronchiolar epithelial lesions induced in the premature rabbit neonate by short periods of artificial ventilation. Acta Pathol Microbiol Scand [A] 88: 359–367
Nilsson R, Grossmann G, Robertson B (1980) Pathogenesis of neonatal lung lesions induced by artificial ventilation: evidence against the role of barotrauma. Respiration 40: 218–225
Nohara K, Berggren P, Curstedt T, Grossmann G, Nilsson R, Robertson B (1986) Correlations between physical and physiological properties of various preparations of lung surfactant. Eur J Respir Dis 69: 321–335
Rigaut J-P, Robertson B (1986) Quantitative evaluation of neonatal lung expansion with automated image analysis. Pediatr Pathol 6: 11–24
Robertson B, Berry D, Curstedt T, Grossmann G, Ikegami M, Jacobs H, Jobe A, Jones S (1985) Leakage of protein in the immature rabbit lung: effect of surfactant replacement. Respir Physiol 61: 265–276
Robertson B, Noack G, Bevilacqua G, Berggren P, Cosmi EV, Curstedt T, Grossmann G (1986) Surfactant replacement in severe neonatal respiratory distress syndrome. In: Vignali M, Cosmi EV, Luerti M (eds) Diagnosis and treatment of fetal lung immaturity. Masson, Milan, pp 193–197
Suzuki Y, Nakai E, Ohkawa K (1982) Experimental studies on the pulmonary surfactant. Reconstitution of surface-active material. J Lipid Res 23: 53–61
Suzuki Y, Curstedt T, Grossmann G, Kobayashi T, Nilsson R, Nohara K, Robertson B (1986) The role of the low-molecular weight (≤15000 daltons) apoproteins of pulmonary surfactant. Eur J Respir Dis 69: 336–345
Takahashi A, Fujiwara T (1986) Proteolipid of bovine lung surfactant: its role in surfactant function. Biochem Biophys Res Commun 135: 527–532
Whitsett JA, Ohning BL, Ross G, Meuth J, Weaver T, Holm BA, Shapiro DL, Notter RH (1986) Hydrophobic surfactant-associated protein in whole lung surfactant and its importance for biophysical activity in lung surfactant extracts used for replacement therapy. Pediatr Res 20: 460–467
Yu S-H, Possmayer F (1986) Reconstitution of surfactant activity by using the 6 kDa apoprotein associated with pulmonary surfactant. Biochem J 236: 85–89
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Robertson, B., Curstedt, T., Grossmann, G. et al. Prolonged ventilation of the premature newborn rabbit after treatment with natural or apoprotein-based artificial surfactant. Eur J Pediatr 147, 168–173 (1988). https://doi.org/10.1007/BF00442216
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00442216