Effect of NADPH oxidase inhibition on cardiopulmonary bypass-induced lung injury

被引:39
作者
Dodd-o, JM
Welsh, LE
Salazar, JD
Walinsky, PL
Peck, EA
Shake, JG
Caparrelli, DJ
Ziegelstein, RC
Zweier, JL
Baumgartner, WA
Pearse, DB
机构
[1] Johns Hopkins Med Inst, Dept Anesthesia & Crit Care, Div Pulm & Crit Care Med, Baltimore, MD 21287 USA
[2] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21287 USA
[3] Johns Hopkins Med Inst, Dept Surg, Div Cardiac Surg, Baltimore, MD 21287 USA
[4] Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21287 USA
[5] Ohio State Univ, Coll Med, Davis Heart & Lung Res Inst, Ctr Biomed Electron Paramagnet Resonance Spect &, Columbus, OH 43210 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2004年 / 287卷 / 02期
关键词
diphenyleneiodonium; apocynin; reflection coefficient; pig; endothelium; hypoxia-reoxygenation; tumor necrosis factor; interleukin-6;
D O I
10.1152/ajpheart.01138.2003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cardiopulmonary bypass (CPB) causes acute lung injury. Reactive oxygen species (ROS) from NADPH oxidase may contribute to this injury. To determine the role of NADPH oxidase, we pretreated pigs with structurally dissimilar NADPH oxidase inhibitors. Low-dose apocynin (4-hydroxy-3-methoxy-acetophenone; 200 mg/kg, n = 6), high-dose apocynin (400 mg/kg n = 6), or diphenyleneiodonium (DPI; 8 mg/kg) was compared with diluent (n = 8). An additional group was treated with indomethacin (10 mg/kg, n = 3). CPB was performed for 2 h with deflated lungs, complete Pulmonary artery occlusion, and bronchial artery ligation to maximize lung injury. Parameters of pulmonary function were evaluated for 25 min following CPB. Blood chemiluminescence indicated neutrophil ROS production. Electron paramagnetic resonance determined the effect of apocynin and DPI on in vitro pulmonary endothelial ROS production following hypoxia-reoxygenation. Both apocynin and DPI attenuated blood chemiluminescence and post-CPB hypoxemia. At 25 min post-CPB with FIO2 = 1. arterial Po-2 (Pa-o2) averaged 52 +/- 5. 162 +/- 54, 335 +/- 88, and 329 +/- 119 mmHg in control, low-dose apocynin, high-dose apocynin, and DPI-treated groups. respectively (P < 0.01). Indomethacin had no effect. Pa-O2 correlated with blood chemiluminescence measured after drug administration before CPB (R = -0.60 P < 0.005). Neither apocynin nor DPI prevented the increased tracheal pressure, plasma cytokine concentrations (tumor necrosis factor-alpha and IL-6), extravascular lung water, and Pulmonary vascular protein permeability observed in control pigs. NADPH oxidase inhibition, but not xanthine oxidase inhibition. significantly blocked endothelial ROS generation following hypoxia-reoxygenation (P < 0.05). NADPH oxidase-derived ROS contribute to the severe hypoxemia but not to the increased cytokine generation and pulmonary vascular protein permeability, which occur following CPB.
引用
收藏
页码:H927 / H936
页数:10
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