Restoration of lung pressure-volume characteristics with various phospholipids.

Abstract

Summary: The surfactant depleted adult rat lung model previously reported by us was used to determine the ability of certain phospholipids (PL), either singly or in combination, to restore the lung pressure-volume (PV) characteristics to normal. Seventy-one adult rats were used for this study. Before depletion of surfactant, a PV curve was obtained and the mean percent total lung capacity (% TLC) at 5 cm H2O on the deflation limb was 53.8. Maximal removal of surfactant was done by repeated lung washings, and a second PV curve was obtained (mean % TLC was 9.2). Various PL suspensions were prepared by sonication of dipalmitoyl lecithin and another PL in saline at a molar ratio of 9:1. The final concentration was 5 mg DPL/ml. Each suspension was instilled directly into the trachea and the lung was ventilated for 5 min at a rate of 40/min, a volume of 7 ml, PEEP of 5 cm H2O, and an inspiration to total cycle ratio of 0.4. A third PV curve was then done. For all PV curves, the percent of original TLC at 5 cm H2O was calculated. The % TLC at 5 cm H2O after treatment with phospholipid suspensions, showed: DPL/unsaturated phosphatidyl glycerol (u-PG), 37.2; DPL/unsaturated phosphatidyl inositol (u-PI), 28.3; DPL, 25.8; DPL/unsaturated phosphatidyl serine (u-PS), 25.7; DPL/unsaturated lecithin (u-Lecithin), 24.1; DPL/dipalmitoyl phosphatidyl glycerol (DPPG), 7.7; and an analog of DPL from the University of Rhode Island (URI analog), 20.1. Although six of the seven suspensions possessed varying ability to restore the PV characteristics toward normal, none was as effective as natural surfactant which gave a mean of 46.8.Speculation: Of the seven phospholipid mixtures, DPL/u-PG produced the most improvement in lung stability. Furthermore, surface tension measurements of DPL/u-PG showed normal surface activity. This suggests that DPL in combination with u-PG might afford a basis for development of a synthetic surfactant for treatment of respiratory distress syndrome (RDS).