ABSTRACT. Modified natural porcine surfactant was mixed with edema fluid sampled from the airways of hyperoxia-exposed adult rabbits. By varying the concentration of surfactant lipids (10, 25, and 50 mg/mL) and edema fluid proteins (0-280 mg/mL), we obtained a series of preparations with protein to surfactant lipid weight ratios ranging from 0 to 11.2. The surfactant activity of these various mixtures was analyzed with a pulsating bubble (at a lipid concentration of 1 0 mg/mL) or in experiments on immature newborn rabbits (at lipid concentrations of 25 or 50 mg/mL). For the latter purpose, animals were delivered at a gestational age of 27 d and ventilated with a standardized sequence of insufflation pressures after receiving 0.1 mL of the surfactant-edema sample into the airways a t birth. Nearly complete in vitro inhibition of surfactant (markedly delayed film adsorption and a minimum surface tension of 23 mN/m during pulsation) was observed at a protein to surfactant lipid ratio of 4.5. Under in vivo conditions, nearly complete surfactant inhibition (tidal volumes reduced to less than 20% of the values for littermates ventilated with the same pressure after receiving surfactant without admixture of edema fluid) was documented at a protein to surfactant lipid ratio of 11.2. Our data suggest that the functional properties of an immature neonatal lung, in which serum proteins tend to leak into the airspaces after the onset of ventilation, depend on the stoichiometric relation between surfactant lipids and inhibitory proteins in the lung liquid. (Pediatr Res 29: 353-356, 1991) Abbreviations P/L, protein to surfactant lipid Surfactant CK, modified natural porcine surfactant Respiratory distress syndrome of the premature newborn infant is the result of at least two pathophysiologic mechanisms. One is a deficiency of lung surfactant phospholipids and associated proteins, the other is a leakage of serum proteins into the airspaces (1). These two factors are intertwined, inasmuch as ventilation of surfactant-deficient lungs causes epithelial disrup-

The surfactant-associated proteins SP-B (8.7 kD) and SP-C (4.2 kD) are hydrophobic polypeptides that accelerate the adsorption of the surfactant lipids to an air-liquid interface (1-5). These proteins seem to be essential components of "natural" surfactant preparations for replacement therapy (I). Because the rapid adsorption of lung surfactant is a prerequisite of normal respiratory adaptation in the neonatal period (6,7), we wondered whether selective blocking of one of these proteins in the mature neonatal lung would lead to pulmonary maladaptation or to structural and functional abnormalities similar to those charac-

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Hydrochloric acid (0.1 N, 5.0 ml.kg-1 in total) was administered intratracheally to 28 adult rabbits anesthetized with pentobarbital and mechanically ventilated with pure oxygen. When the PaO2 decreased to 14.1 +/- 2.8 kPa (mean +/- s.d.), the PaCO2 increased to 8.9 +/- 2.5 kPa, and the minute ventilation (VE) decreased to 51 +/- 8% of the baseline value, animals were divided into 4 groups. The deteriorated values did not improve in the non-treated (control) animals, whereas the animals treated with lung lavage and surfactant replacement showed a significant increase in PaO2 to 35.1 +/- 12.2 kPa, and maintained lower PaCO2 and larger VE than the controls. These parameters showed no significant improvement with surfactant replacement alone, and deteriorated further with lung lavage alone. The minimum surface tension (gamma min) of the edema fluid that accumulated in the airways after acid administration was 22.5 +/- 1.7 mN.m-1, and was not lowered by adding surfactant preparation (10 mg.ml-1) whose original gamma min was less than 2 mN.m-1. We concluded that surfactant inhibition by edema fluid was a cause of respiratory failure, and that lung lavage followed by surfactant replacement might be of therapeutic value for acid aspiration.

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