Inactivation of exogenous surfactant by pulmonary edema fluid

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 10 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 at 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.