Effect of NADPH oxidase inhibition on cardiopulmonary bypass-induced lung injury
| Autor: | David B. Pearse, Jay G. Shake, David J. Caparrelli, Peter L. Walinsky, Jay L. Zweier, Eric A. Peck, Laura E. Welsh, William A. Baumgartner, Jorge D. Salazar, Jeffrey M. Dodd-o, Roy C. Ziegelstein |
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| Rok vydání: | 2004 |
| Předmět: |
Lung Diseases
Endothelium Swine Physiology Blood Pressure Pulmonary Artery Lung injury Pharmacology law.invention chemistry.chemical_compound law Physiology (medical) Pressure medicine Cardiopulmonary bypass Animals Enzyme Inhibitors Lung chemistry.chemical_classification Reactive oxygen species Oxidase test Cardiopulmonary Bypass NADPH oxidase biology Pulmonary Gas Exchange business.industry NADPH Oxidases Organ Size Hypoxia (medical) Cell Hypoxia Blood Cell Count Oxygen Trachea surgical procedures operative medicine.anatomical_structure Hematocrit chemistry Luminescent Measurements Apocynin Immunology biology.protein Endothelium Vascular medicine.symptom Reactive Oxygen Species Cardiology and Cardiovascular Medicine business |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 287:H927-H936 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.01138.2003 |
| Popis: | 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 Fi(O(2)) = 1, arterial Po(2) (Pa(o(2))) averaged 52 +/- 5, 162 +/- 54, 335 +/- 88, and 329 +/- 119 mmHg in control, low-dose apocynin, high-dose apocynin, and DPI-treated groups, respectively (P0.01). Indomethacin had no effect. Pa(O(2)) correlated with blood chemiluminescence measured after drug administration before CPB (R = -0.60, P0.005). 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 (P0.05). 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. |
| Databáze: | OpenAIRE |
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