Effect of Ono-EI-600 elastase inhibitor on high-tidal-volume-induced lung injury in rats

Abstract

We tested the effect of Ono-EI-600, an elastase inhibitor that suppresses cytokine release, on ventilator-induced lung injury in a rat model. After Wistar rats (aged 8-11 weeks) were anesthetized and tracheostomized, they were randomly assigned to four groups: high tidal volume (VT) group (H group: n = 10) receiving peak inspiratory pressure (PIP) 30cmH2O for 240min; high VT with drug group (HD group: n = 10) receiving the same ventilation settings as H group and also intravenous infusion 10mg·kg-1·h-1 of Ono-EI-600 during the protocol; the lower VT group (L group: n = 5) receiving PIP 10cmH2O for 240min; and control group (C group: n = 5) receiving the same ventilation as L group for 30min. The cytokine levels (IL-6 and CINC-1) in the bronchoalveolar lavage fluid (BALF) of the H group were significantly higher than those of the C and L groups (P < 0.05). However, for the H and HD groups, no differences were found in arterial blood gas data, cytokine levels in BALF, and histological injury scores. Our experiment provided no evidence that elastase inhibitor Ono-EI-600 protects against lung injury induced by high VT ventilation. © JSA 2006.