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Prolonged ventilation of the premature newborn rabbit after treatment with natural or apoprotein-based artificial surfactant

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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.

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Abbreviations

DPPC:

dipalmitoylphosphatidylcholine

DPPG:

dipalmitoylphosphatidylglycerol

RDS:

respiratory distress syndrome

Vv :

volume density

CV:

coefficient of variation

dVT :

tidal volume reduction

K:

kilodalton(s)

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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

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