Effects of Surfactant Subtractions on Preterm Rabbit Lung Function

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Abstract
Surfactant isolated from adult rabbits was separated into large aggregate forms (LA) and small aggregate forms (SA) by centrifugation at 40 000 X g. LA contain SP-A and the surfactant lipophilic proteins SP-B and SP-C and are surface-active in vitro, whereas SA lack the surfactant proteins and have poor surface properties. Premature rabbits were treated with LA or SA and ventilated to evaluate the effects of LA and SA in vivo. There were dose-response effects of LA at doses between 10 and 50 mg total lipid/kg: dynamic compliances increased from 0.4 to 0.8 mL/cm H2O/kg and pressure-volume curves improved significantly, whereas SA did not improve any of the measurements at any dose. Organic solvent extracts of SA made up into LA also did not improve in vivo function. When 1.5% SP-B and SP-C isolated from calf surfactant was added to organic solvent extracts of SA, the surfactant had good in vitro surface properties and increased maximum lung volumes. However, this surfactant did not improve dynamic compliances or lung stability on pressurevolume curves. Because the lipids from SA seemed to limit the compliance response, we tried to identify differences in lipids from LA and SA. Phospholipids from SA reconstituted with SP-BC did not function well in vivo, whereas phospholipids from LA with SP-BC were similar to LA surfactant. The neutral lipid fractions from LA or SA did not contribute very much to or inhibit function. Fatty acid composition of the phospholipids and phosphatidylcholine from LA and SA were not remarkably different. We conclude that subtle compositional differences in the phospholipids or difficulties with reconstriction of the lipids with SP-BC prevents in vivo function of SA surfactant.