Am. J. Respir. Crit. Care Med., Volume 158, Number 3, September 1998, 840-845

Aerosolized Surfactant Improves Pulmonary Function in Endotoxin-induced Lung Injury

CHARLES LUTZ, DAVID CARNEY, CHRISTINE FINCK, ANTHONY PICONE, LOUIS A. GATTO, ANDREW PASKANIK, EDWARD LANGENBACK, and GARY NIEMAN

SUNY Health Science Center at Syracuse, Department of Surgery, Syracuse, New York; SUNY Health Science Center at Stony Brook, Stony Brook, New York; and SUNY College at Cortland, Department of Biological Sciences, Cortland, New York

Surfactant dysfunction is a primary pathophysiologic component in patients with adult respiratory distress syndrome (ARDS). In this study we tested the efficacy of aerosolized surfactant (Sf ) replacement in a severe lung injury model of endotoxin-induced ARDS. Twenty-one certified healthy pigs were anesthetized, surgically prepared for measurement of hemodynamic and lung function, then randomized into one of four groups: (1) control (n = 5), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 6), infused with Escherichia coli LPS (100 µg/kg) without positive end- expiratory pressure (PEEP) and ventilated with a nonhumidified gas mixture of 50% N₂O and 50% O₂; (3) LPS + PEEP (n = 4), infused with LPS, placed on PEEP (7.5 cm H₂O), and ventilated with a humidified gas mixture; and (4) LPS + PEEP + Sf (n = 6), infused with LPS, placed on PEEP, and ventilated with aerosolized Sf (Infasurf, ONY, Inc.). All animals were studied for 6 h. Arterial PO₂ significantly decreased in both the LPS and LPS + PEEP groups (LPS + PEEP = 74 ± 19 mm Hg; LPS = 74 ± 19 mm Hg, p < 0.05) while venous admixture ( S/ T) increased in these groups (LPS + PEEP = 43.3 ± 3.9%; LPS = 47.7 ± 11%, p < 0.05) as compared with the control group. PEEP + Sf reduced the fall in PO₂ (142 ± 20 mm Hg) and rise in S/ T (15.1 ± 3.6%) caused by LPS. Delayed induction of PEEP (2 h following LPS) did not significantly improve any parameter over the LPS group without PEEP in this ARDS model. LPS without PEEP (3.4 ± 0.2 cells/6,400 µm²) caused a marked increase in the total number of sequestered leukocytes in the pulmonary parenchyma as compared with the control group (1.3 ± 0.1 cells/6,400 µm²). LPS + PEEP + Sf (2.3 ± 0.2 cells/6,400 µm²) significantly decreased while LPS + PEEP significantly increased (4.0 ± 0.2 cells/6,400 µm²) the total number of sequestered leukocytes as compared with the LPS without PEEP group. In summary, aerosolized surfactant replacement decreased leukocyte sequestration and improved oxygenation in our porcine model of endotoxin-induced lung injury.

This article has been cited by other articles:

				T. A. Russo, Z. Wang, B. A. Davidson, S. A. Genagon, J. M. Beanan, R. Olson, B. A. Holm, P. R. Knight 3rd, P. R. Chess, and R. H. Notter Surfactant dysfunction and lung injury due to the E. coli virulence factor hemolysin in a rat pneumonia model Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L632 - L643. [Abstract] [Full Text] [PDF]

				L. A. Augusto, J. Li, M. Synguelakis, J. Johansson, and R. Chaby Structural Basis for Interactions between Lung Surfactant Protein C and Bacterial Lipopolysaccharide J. Biol. Chem., June 21, 2002; 277(26): 23484 - 23492. [Abstract] [Full Text] [PDF]

				L. Augusto, K. Le Blay, G. Auger, D. Blanot, and R. Chaby Interaction of bacterial lipopolysaccharide with mouse surfactant protein C inserted into lipid vesicles Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L776 - L785. [Abstract] [Full Text] [PDF]

				M. A. KANDLER, K. von der HARDT, E. SCHOOF, J. DOTSCH, and W. RASCHER Persistent Improvement of Gas Exchange and Lung Mechanics by Aerosolized Perfluorocarbon Am. J. Respir. Crit. Care Med., July 1, 2001; 164(1): 31 - 35. [Abstract] [Full Text] [PDF]

				J. K. Wright, F. N. Nwariaku, J. Clark, J. C. Falck, T. Rogers, and R. H. Turnage Effect of Diabetes Mellitus on Endotoxin-Induced Lung Injury Arch Surg, December 1, 1999; 134(12): 1354 - 1359. [Abstract] [Full Text] [PDF]