ASPIRATION-INDUCED LUNG INJURY - ROLE OF COMPLEMENT

Objectives: To examine the role of complement in the development of ac id aspiration-induced lung injury in the rat. It was postulated that i nhibition or depletion of complement attenuates aspiration-induced lun g injury. Design: Controlled animal trial. Setting: Animal Laboratory, Jefferson Medical College, Philadelphia, PA. Subjects: Anesthetized r ats. Interventions: Aspiration was induced by the intratracheal admini stration of 0.2 mL of 0.1 N hydrochloric acid (n = 7) and lung injury was evaluated by determining water content, myeloperoxidase activity, protein concentration, and leukocyte count in bronchoalveolar lavage f luid, Muscle Po-2 was directly measured using a thin-film chamber oxyg en sensor and serum tumor necrosis factor-a was assayed by enzyme-link ed immunosorbent assay. The effect of complement inhibition by recombi nant human soluble complement receptor type 1 (n = 8) or complement de pletion by cobra venom factor (n = 7) on lung injury was evaluated. Me asurements and Main Results: Acid aspiration induced pulmonary leukose questration, edema, and a microvascular permeability defect, along wit h tissue hypoxia. Pretreatment with soluble complement receptor type 1 (complement inhibition) or cobra venom factor (complement depletion) significantly reduced lung edema (-61 +/- 7%; p < .05), eliminated pro tein accumulation in bronchoalveolar lavage fluid (p < .01), and impro ved (p < .05) tissue oxygenation. In contrast, there was no effect of soluble complement receptor type 1 or of cobra venom factor on leukose questration. Conclusions: Acid aspiration induces lung injury through a complement-dependent mechanism that leads to microvascular permeabil ity defects. Therefore, the possibility that complement inhibitors may have a salutary effect in humans with aspiration-induced lung injury should be investigated.