PULMONARY SURFACTANT FUNCTION FOLLOWING ENDOTOXIN - EFFECTS OF EXOGENOUS SURFACTANT TREATMENT

In a porcine model of endotoxin-induced adult respiratory distress syn drome (ARDS) we tested the hypothesis that the severity of lung injury would vary with the concentration of endotoxin and that reestablishme nt 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 gre atly in animal models of ARDS. This has created discrepancies in the l iterature that may be due in part to a difference in the severity of t he pulmonary lesion, Yorkshire pigs were anesthetized, placed on a ven tilator, and surgically prepared for hemodynamic and lung function mea surements. Rigs received either 25 (25LPS) or 50 (5OLPS) mu g/kg of Es cherichia coil lipopolysaccharide (LPS) followed by exogenous surfacta nt (SURF, 100 mg/kg) instillation, and were randomized into five group s: Control = sham LPS (n = 4); 25LPS (n = 6); 50LPS (n = 6); 25LPS + S URF (n = 5); and 50LPS + SURF (n = 6). Treatments were followed by his tological and surfactant function evaluation. Histological evaluation showed the hallmarks of ARDS. Pulmonary surfactant function assessed b y surface tension minimum (y(min)) 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). Exogen ous surfactant reduced y(min) in the 25LPS + SURF group (9+/-2 dyne/cm , p <.05 vs. 25LPS) but not in the 50LPS + SURF group (20 +/- 1 dyne/c m,p <.05 vs. Control and 25LPS + SURF). Surfactant treatment was more effective in reestablishing normal surfactant function in animals subj ected to a low dose of endotoxin, compared with animals receiving a hi gher dose.