Effect of Ono-EI-600 elastase inhibitor on high-tidal-volume-induced lung injury in rats.
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 (V(T)) group (H group: n = 10) receiving peak inspiratory pressure (PIP) 30 cmH(2)O for 240 min; high V(T) with drug group (HD group: n = 10) receiving the same ventilation settings as H group and also intravenous infusion 10 mg x kg(-1) x h(-1) of Ono-EI-600 during the protocol; the lower V(T) group (L group: n = 5) receiving PIP 10 cmH(2)O for 240 min; and control group (C group: n = 5) receiving the same ventilation as L group for 30 min. 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 V(T) ventilation.
Fujita
Yasuki
Y
Intensive Care Unit, Osaka University Hospital, Osaka, Japan.
Fujino
Yuji
Y
Maeda
Yoshiko
Y
Uchiyama
Akinori
A
Mashimo
Takashi
T
Nishimura
Masaji
M
D000818:Animals; D001784:Blood Gas Analysis; D016207:Cytokines / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D008297:Male; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000009:adverse effects*; D013449:Sulfonamides / Q000494:pharmacology*; D013990:Tidal Volume / Q000502:physiology*
D016207:Cytokines; D011480:Protease Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D010196:Pancreatic Elastase; D005998:Glycine