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

Introduction

The acute respiratory distress syndrome (ARDS) is charactcrized by diffuse injury to the endothelial and epithelial surfaces of the lung leading to severe respiratory failure. Alterations in the surfactant system and activation of the contact system of coagulation are major contributors to the pathophysiology of ARDS. C1-inhibitor (C1-INH) is the main inhibitor of contact activation and the only known inhibitor of classical pathway complement activation. The aim of this study was to investigate the effects of C1-inhibitor administration and rSP-C surfactant application on oxygenation and lung histology in an ARDS-model.

Methods

Thirty-six male Sprague Dawley rats were subjected to repetitive lung lavage with isotonic saline solution. Three experimental groups and two control groups were studied: Group 1 and 2 served as controls without any treatment. Animals of group 1 were sacrificed 60 min after the last lavage procedure (p.l.). Animals of group 3-5 received 200 U /kg body weight (b.w.) Cl-INH (Centeon, Germany) intravenously (group 3), 25 mg/kg b.w. rSP-C Surfactant (Byk Gulden, Germany) intratracheally (group 4) or both (group 5) at 60 min p.l. Blood gases were determined 120, 150, 180 and 210 min p.l. All animals of group 2-5 were sacrificed at 210 min p.l. and the lungs were excised for histological examination. Hyaline membrane formation, distribution and severity of intraalveolar neutrophil (PMN) accumulation and the severity of intraalveolar and perivascular hemorrhage were graded semiquantitatively using a scale from 0 to 4+.

Results

At 210min p.l. pO₂ values of group 4 (456 ± 74 mmHg) and group 5 (387 ± 155 mmHg) were significantly higher than in group 3 (120 ± 103 mmHg) or in controls (63 ± 12 mmHg). Hyaline membrane formation was significantly reduced in group 4 and 5. The grading for PMN infiltration was significantly lower in animals who received C1-INH (group 3 = 2.0, group 5 = 2.3) than in controls (group 2 = 2.7) or in animals treated with surfactant only (group 4 = 3.3). The severity of intraalveolar hemorrhage and edema were significantly reduced in group 3 and highest in group 4.

Conclusion

Surfactant application was effective in improving pO₂ which was related to the reduction of hyaline membrane formation. C1-INH administration had no significant effect on pO₂ and hyaline membrane formation but was effective in reducing PMN infiltration, intraalveolar hemorrhage and edema formation.