Effects of C1 inhibitor and r-SP-C surfactant on oxygenation and histology in rats with lavage-induced acute lung injury.

OBJECTIVE: To assess the effects of C1 inhibitor (INH) administration and r-SP-C surfactant application on oxygenation and lung histology in an acute respiratory distress syndrome model. DESIGN AND SETTING: Randomized, controlled experimental study in an animal research laboratory. MATERIAL: 36 adult male Sprague-Dawley rats. INTERVENTIONS: Animals were subjected to repetitive lung lavage. Four experimental groups and two control groups were studied: groups 1 and 2 served as controls. Animals of groups 3-6 received 200 U/kg body weight C1-INH (group 3), 25 mg/kg r-SP-C surfactant (group 4) or both (group 5) at 60 min postlavage (pl). Animals of group 6 were treated with 200 U/kg C1-INH1 at 10 min pl. Animals of group 1 were killed 60 min (min) pl, animals of groups 2-6 were killed at 210 min pl. Thereafter the lungs were excised for histological examination. MEASUREMENTS AND RESULTS: Hyaline membrane formation, intra-alveolar neutrophil (PMN) accumulation and intra-alveolar/perivascular haemorrhage were graded semiquantitatively (0-4). Blood gases were determined 120, 150, 180 and 210 min pl. At 210 min pl pO(2) in group 4 (456+/-74 mmHg) and group 5 (387+/-155 mmHg) was significantly higher than in controls (72+/-29 mmHg) or after C1-INH monotherapy (group 3: 120+/-103, group 6: 63+/-12 mmHg). PMN infiltration after C1-INH monotherapy was significantly less severe than in controls. The combination of r-SP-C surfactant and C1-INH led to significantly lower PMN infiltration than surfactant monotherapy. CONCLUSION: In this lavage-induced acute respiratory distress syndrome model the administration of C1-INH might be followed by a higher clinical efficacy of exogenously supplied recombinant SP-C surfactant.

Pulmonary surfactant: functions, abnormalities and therapeutic options.

The first successful clinical pilot studies of surfactant replacement were published about 20 years ago as a logical extension of experimental studies showing beneficial effects in pre-term animals. The efficacy of this therapy for immature new-borns has been confirmed in various controlled trials and surfactant therapy is now part of the routine management of the infant respiratory distress syndrome. During the last decade there has been growing insight into the functional role of surfactant components and the mechanisms by which exogenous surfactant exerts its therapeutic effects on lung mechanics, gas exchange and host defence. Of particular interest in this context is the essential role that surfactant-associated proteins play in the surface tension-limiting ability of surfactant, as well as their contribution to pulmonary defence. Indications for surfactant replacement have widened in recent years and promising results have been obtained for adult conditions such as the acute respiratory distress syndrome (ARDS), pneumonia, chronic obstructive and allergic lung diseases. This review outlines the complexity of the surfactant system and describes its basic biophysics, physiology and biochemistry. Problems related to the development of exogenous surfactant preparations, the exploration of clinical targets for surfactant therapy and pathophysiological mechanisms interfering with surfactant function in various forms of lung disease will be discussed.