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

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. Randomized, controlled experimental study in an animal research laboratory. 36 adult male Sprague-Dawley rats. 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. 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. 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.