Pulmonary surfactant function following endotoxin: effects of exogenous surfactant treatment.

Abstract

In a porcine model of endotoxin-induced adult respiratory distress syndrome (ARDS) we tested the hypothesis that the severity of lung injury would vary with the concentration of endotoxin and that reestablishment of normal surfactant function with exogenous surfactant would vary with the severity of lung injury. The therapeutic effects of exogenous surfactant treatment on pulmonary surfactant function have varied greatly in animal models of ARDS. This has created discrepancies in the literature that may be due in part to a difference in the severity of the pulmonary lesion. Yorkshire pigs were anesthetized, placed on a ventilator, and surgically prepared for hemodynamic and lung function measurements. Pigs received either 25 (25LPS) or 50 (50LPS) micrograms/kg of Escherichia coli lipopolysaccharide (LPS) followed by exogenous surfactant (SURF, 100 mg/kg) instillation, and were randomized into five groups: Control = sham LPS (n = 4); 25LPS (n = 6); 50LPS (n = 6); 25LPS + SURF (n = 5); and 50LPS + SURF (n = 6). Treatments were followed by histological and surfactant function evaluation. Histological evaluation showed the hallmarks of ARDS. Pulmonary surfactant function assessed by surfaced tension minimum (Ymin) was significantly (P < .05) elevated in both the 25LPS (20.2 +/- 2, dyne/cm) and 50LPS (19 +/- 3, dyne/cm) groups as compared with the Control group (10 +/- 1, dyne/cm). Exogenous surfactant reduced Ymin in the 25LPS + SURF group (9 +/- 2 dyne/cm, p < .05 vs. 25LPS) but not in the 50LPS + SURF group (20 +/- 1 dyne/cm, p < .05 vs. Control and 25LPS + SURF). Surfactant treatment was more effective in reestablishing normal surfactant function in animals subjected to a low dose of endotoxin, compared with animals receiving a higher dose.