A leukocyte elastase inhibitor reduces thrombin-induced pulmonary oedema in the rat: Mechanisms of action

被引:3
作者
Ahn, CM
Sandler, H
Saldeen, T
机构
[1] Uppsala Univ, Dept Forens Med, S-75137 Uppsala, Sweden
[2] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea
关键词
leukocyte elastase inhibitor; ICI 200,355; thrombin; microembolism; rat; pulmonary oedema; myeloperoxidase; adult respiratory distress syndrome;
D O I
10.1006/pupt.1998.9999
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effect of a selective leukocyte elastase inhibitor, ICI 200,355, on thrombin-induced pulmonary oedema was studied in rats. Thrombin administration produced an increase in lung weight (P<0.05), wet weight/ dry weight ratio (P<0.05), and relative lung water content (P<0.05). The lung weight increase nas reduced by the elastase inhibitor in doses of 2000, 200 and 20 mu g/kg per h (P<0.05), but not by 2 mu g/kg per h. A dose of 20 mu g/ kg per h seems to be optimal, since 10-fold and 100-fold increases in dose did not further improve the effect. Free elastase activity in lung tissue was higher after thrombin infusion than in controls, but was not depleted by the elastase inhibitor in vivo (P<0.05). This elastase activity in the lung was, however, inhibited by the elastase inhibitor in vitro, indicating that the inhibitor can block extracellular, but not intracellular elastase activity. Thrombin infusion resulted in a significant decrease in plasma elastase inhibitory capacity (P<0.05), which was depleted by the elastase inhibitor (20 mu g/kg per h) (P<0.05). Myeloperoxidase activity was significantly increased in lung tissue after thrombin infusion (P<0.05). Lung myeloperoxidase activity 5 min after thrombin infusion was not affected by the elastase inhibitor, but the inhibitor induced a further increase in myeloperoxidase as seen 90 min after thrombin infusion, indicating that the effect of this inhibitor on pulmonary oedema is not due to reduction of leukocyte infiltration in the lungs, but may partly be exerted by prevention of neutrophil destruction. (C) 1998 Academic Press.
引用
收藏
页码:291 / 299
页数:9
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