Developing artificial surfactant containing membrane-fusing substance and application for meconium aspiration syndrome

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In rats with experimental meconium aspiration syndrome, administration of porcine surfactant (200 mg/kg) improved the PaO_2 from 100 mmHg to 300 mmHg, but the effect was only transient. Supplementation of dextran to surfactant or lung lavage significantly (P<0.05) strengthened the therapeutic effects; the PaO_2 was maintained at about 300 mraHg for 180 min. In rats with experimental acute respiratory distress syndrome caused by acidified milk, inhalation of aerosolized surfactant for 30 min increased the PaO_2 from 90 mmHg to 300 mmHg, but the PaO_2 soon decreased to below 100 mmHg. However, inhalation of aerosolized dextran maintained the PaO_2 at about 300 mmHg. These results indicated hat dextran significantly improves therapeutic effects of surfactant replacement.A synthetic peptide similar to surfactant protein C (SP-C) was developed, and used to prepare synthetic surfactant (SS). The minimum and maximum (γmax) surface tension of SS was about 2 mN/m and 40 mN/m, respectively. The γmax was significantly higher than that of porcine surfactant. Addition of dextran to SS reduced the γmax to about 30 mN/m (NS. vs. porcine surfactant). Tidal volume (TV) of immature newborn rabbits receiving SS (about 10 ml/kg) was significantly better than that receiving phospholipids only. Addtion of dextran to SS impveed the tidal volume to 15 ml/kg, which was still less than procine surfactant. In analyses of SP-C derived from patients with pulmonary alveolar proteinosis, dimeric SP-C yielded larger TV than monomeric form SP-C in immature newborn rabbits, and the TV was not significantly different from that receiving normal SP-C. Addition of dextran to synthetic surfactant or using dimeric SP-C warrants further experiment to develop synthetic surfactant.