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Published on: February 25, 2015
Effect of a neutrophil elastase inhibitor on ventilator-induced lung injury in rats
Do-Hyung Kim1, Jae Ho Chung1, Bong Soo Son1
11 Department of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Pusan, Korea ; 2 Division of Pulmonology, Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea.
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)×10(4) vs. (7.67±1.41)×10(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)×10(4) vs. (3.89±1.05)×10(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.
