Effect of a neutrophil elastase inhibitor on ventilator-induced lung injury in rats

Objective: We hypothesized that pretreatment with sivelestat therapy could attenuate ventilator-induced lung injury (VILI) and lung inflammation in a rat model. Methods: The neutrophil elastase inhibitor was administered intraperitoneally 30 min before and at the initiation of ventilation. The rats were categorized as (I) sham group; (II) VILI group; (III) sivelestat group; (IV) early sivelestat group. Wet-to-dry weight ratio, bronchoalveolar lavage fluid (BALF) neutrophil and protein, tissue malondialdehyde (MDA) and histologic VILI scores were investigated. Results: The ratio of wet-to-dry weight, BALF neutrophil and protein, tissue MDA and VILI scores were significantly increased in the VILI group compared to the sham group [3.85 +/- 0.32 vs. 9.05 +/- 1.02, P<0.001; (0.89 +/- 0.93) x10(4) vs. (7.67 +/- 1.41) x10(4) cells/ mL, P<0.001; 2.34 +/- 0.47 vs. 23.01 +/- 3.96 mg/mL, P<0.001; 14.43 +/- 1.01 vs. 36.56 +/- 5.45 nmol/mg protein, P<0.001; 3.78 +/- 0.67 vs. 7.00 +/- 1.41, P<0.001]. This increase was attenuated in the early sivelestat group compared with the sivelestat group [wet- to- dry ratio: 6.76 +/- 2.01 vs. 7.39 +/- 0.32, P= 0.032; BALF neutrophil: (5.56 +/- 1.13) x10(4) vs. (3.89 +/- 1.05) x10(4) cells/mL, P= 0.021; BALF protein: 15.57 +/- 2.32 vs. 18.38 +/- 2.00 mg/mL, P= 0.024; tissue MDA: 29.16 +/- 3.01 vs. 26.31 +/- 2.58, P= 0.049; VILI scores: 6.33 +/- 1.41 vs. 5.00 +/- 0.50, P= 0.024]. Conclusions: Pretreatment with a neutrophil elastase inhibitor attenuates VILI in a rat model.