Phosphodiesterase type 4 inhibitor prevents acute lung injury induced by cardiopulmonary bypass in a rat model

被引:20
作者
Hamamoto, M
Suga, M
Nakatani, T
Takahashi, Y
Sato, Y
Inamori, S
Yagihara, T
Kitamura, S
机构
[1] Natl Cardiovasc Ctr, Dept Regenerat Med & Tissue Engn, Suita, Osaka 5658565, Japan
[2] Jichi Med Sch, Dept Surg, Minami Kawachi, Tochigi, Japan
[3] Natl Cardiovasc Ctr, Dept Clin Engn, Osaka, Japan
[4] Natl Cardiovasc Ctr, Dept Organ Transplantat, Osaka, Japan
[5] Natl Cardiovasc Ctr, Dept Cardiovasc Surg, Osaka, Japan
关键词
phosphodiesterase type 4 inhibitor; cardiopulmonary bypass; neutrophil activation; rat;
D O I
10.1016/j.ejcts.2004.01.054
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives: Cardiopulmonary bypass (CPB) induces systemic inflammatory response with neutrophil activation and subsequent lung dysfunction. Rolipram. a selective phosphodiesterase type 4 inhibitor, blocks the decrease in levels of cyclic adenosine monophosphate associated with neutrophil activation. Here, we tested the protective effect of rolipram on CPB-induced lung injury in the rat. Methods: Rats were divided into three groups: control (C), rolipram (R) and sham (S). In the C and R groups, animals underwent CPB at a flow rate of 60 ml/kg per min for 60 min followed by another 60-min observation, whereas the S group rats were sustained for 120 min only with median sternotomy and the placement of cannulae for CPB. Rolipram (40 mug/kg per min) was administered to the R group rats by continuous intravenous infusion from 10 min before the establishment of CPB to the end of the experiment. Results: The R and S groups showed significantly higher mean arterial oxygen pressure and lower mean lung wet-to-dry weight ratio compared with those observed in the C group (R: 489 +/- 44 or S: 527 +/- 55 vs. C: 287 +/- 185, and R: 5.0 +/- 0.4 or S: 4.7 +/- 0.3 vs. C: 5.9 +/- 0.5, respectively; P < 0.01). Although CD11b expression levels on circulating neutrophils in the C group doubled after CPB, those in the R and S groups remained almost the same (P = 0.0008). Intrapulmonary tumor necrosis factor-a concentrations (pg/mug protein) in the C group tended to be higher than those observed in the R and S groups (R: 5.2 +/- 2.1, S: 5.0 +/- 2.1 and C: 8.9 +/- 5.4; R vs. C: P = 0.09 and S vs. C: P = 0.08). Pathological study of lungs revealed that more alveolar hemorrhage and neutrophil accumulation were observed in the C group compared to the R and S groups. Conclusions: These results suggest that rolipram prevents acute lung injury via the inhibition of neutrophil activation during and after CPB in this setting of a rat model. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:833 / 838
页数:6
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