Abstract 1919 Poster Session IV, Tuesday, 5/4 (poster 335)

Leakage of proteins into the alveolar space can inhibit surfactant function and worsen respiratory failure in preterm infants. Surface balance studies in our lab showed remarkable surface activity of a synthetic peptide based on the N-terminal domain of human surfactant protein B (SP-B1-25) mixed into to a palmitic acid containing phospholipid dispersion (PL). We tested the inhibition resistance of this and other synthetic surfactant preparations in ventilated surfactant-deficient rats and preterm rabbits: PL, PL + 3% SP-B1-25 (B1-25), PL + 3% full-length SP-B1-78 (B), PL + 1% palmitoylated SP-C1-34 (C), PL + 3% SP-B1-25 + 1% SP-C1-34 (B1-25+C), PL + 3% SP-B1-78+ 1% SP-C34 (B+C), and Survanta. Adult rats were ventilated with 100% oxygen, a tidal volume of 7.5 mL/kg, and a rate of 60/min, and lavaged with saline until the PaO2 dropped below 100 torr, at which time they were treated with 10 mg/kg of human fibrinogen, followed 15 min later by 100 mg/kg of one of the experimental surfactants. After 2 h of ventilation, the rats were killed, pressure volume curves performed, and their lung re-lavaged. The rats treated with B1-25+C, B+C, and B1-25-surfactant maintained highest oxygenation and dynamic compliance values throughout the experiment and had lung volumes on the postmortem pressure-volume curves. Preterm rabbits born at 27 days of gestation were intubated, ventilated with a tidal volume of 10 mL/kg, and treated with 100 mg/kg of surfactant at birth 2 mL/kg of 1:1 diluted fresh frozen plasma (∼50 mg protein/kg) intratracheally at 15 min of age. Preterm rabbits treated with B1-25+C, B+C, and B1-25-surfactant maintained the highest dynamic compliance and lung volume after plasma instillation. These data show that the N-terminal domain of SP-B plays an important role in the resistance of surfactant against inhibition by plasma proteins.

Supported by NIH grant HL55534.