METABOLISM OF EXOGENOUSLY ADMINISTERED SURFACTANT IN THE ACUTELY INJURED LUNGS OF ADULT-RABBITS

Acute lung injury was induced in adult rabbits with a subcutaneous injection of N-nitro-so-N-methylurethane (NNNMU). Clearance of saturated phosphatidylcholine (Sat.PC) from a treatment dose of exogenous surfactant (100 mg/kg) in the injured lungs of these rabbits was similar to normal, control rabbits when measured 24 h after treatment. However, total Sat.PC pool sizes in both the alveolar wash and total lung at this time point were significantly lower for the injured lungs than for the control lungs (p < 0.05), implying altered endogenous surfactant metabolism in response to surfactant treatment in the injured animals. Although both injured and control animals had comparable ratios of small to large surfactant aggregates, as measured by differential centrifugation of alveolar wash 5 min after treatment, by 24 h this ratio had increased 5-fold in the control animals and remained unchanged in the injured animals. This indicated diminished conversion of large surfactant aggregates to the smaller forms in lung injury. In vivo functional studies of these aggregates were performed by intratracheal injection into surfactant-deficient preterm rabbits. Large aggregates from normal adult rabbits given surfactant had superior functional properties than did the surfactant used for treatment alone, which in turn was better than large aggregates isolated from NNNMU-injured rabbits treated with surfactant. This indicates that the alveolar environment influenced the function of the exogenously administered surfactant differently in normal and injured rabbits. We conclude that although the net clearance of a large dose of exogenous surfactant was the same for NNNMU-injured rabbit lungs and normal rabbit lungs, the effects of this material on alveolar surfactant metabolism were different. These effects may be important when considering treatment of acute lung injury with exogenous surfactant.