Neutrophil Elastase Inhibitor, Sivelestat, Attenuates Acute Lung Injury After Cardiopulmonary Bypass in the Rabbit Endotoxemia Model Fuminori Wakayama,

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Neutrophil Elastase Inhibitor, Sivelestat, Attenuates Acute Lung Injury After Cardiopulmonary Bypass in the Rabbit Endotoxemia Model Fuminori Wakayama, MD, Ikuo Fukuda, MD, Yasuyuki Suzuki, MD, Norihiro Kondo, MD The Annals of Thoracic Surgery Volume 83, Issue 1, Pages 153-160 (January 2007) DOI: 10.1016/j.athoracsur.2006.08.023 Copyright © 2007 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Time course of all groups in the rabbit model for cardiopulmonary bypass. (CPB = cardiopulmonary bypass; LPS = lipopolysaccharide [LPS] group; EI = EI group.) The Annals of Thoracic Surgery 2007 83, 153-160DOI: (10.1016/j.athoracsur.2006.08.023) Copyright © 2007 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 (A) Ratio of Pao2/Fio2 (mm Hg), (B) plasma elastase activity, and (C) plasma interleukin-8 level before, during, and after cardiopulmonary bypass (CPB) for four groups. *Indicates significant differences (p < 0.05) between control and other groups at specific time points (unpaired t statistic). (LPS = lipopolysaccharide; EI = EI group.) The Annals of Thoracic Surgery 2007 83, 153-160DOI: (10.1016/j.athoracsur.2006.08.023) Copyright © 2007 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 (A) Polymorphonuclear neutrophil count in bronchoalveolar (proximal) areas and alveolar (peripheral) areas are expressed as the number of neutrophils in one field (×400) of fixed lung tissue. (B) Myeloperoxidase activity per gram of pulmonary tissue is expressed as units per gram. Data are expressed as means ± standard error of the mean. *Indicates significant differences (p < 0.05) between control and other groups (unpaired t statistic). #Indicates significant differences (p < 0.05) between LPS+CPB group vs LPS and El group (unpaired t statistic). (LPS = lipopolysaccharide; CPB = cardiopulmonary bypass; EI = EI group.) The Annals of Thoracic Surgery 2007 83, 153-160DOI: (10.1016/j.athoracsur.2006.08.023) Copyright © 2007 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Photomicrographs (original magnification ×400, hematoxylin and eosin stain) of fixed lung tissue taken after euthanasia. (A) Control group. Mild accumulation in alveolar septa and slight alveolar septal edema is visible in alveolar areas. (B) Lipopolysaccharide (LPS) group. Moderate PMN accumulation in the alveolar septa accompanied by mild alveolar septal edema is observed. (C) LPS+CPB (cardiopulmonary bypass) group. Severe polymorphonuclear neutrophil (PMN) accumulation in alveolar septa is accompanied by severe alveolar septal edema and moderate transmigration into alveolar space. Alveolar hemorrhage (not shown in this slide) and aggregation of PMNs in capillaries was also observed. (D) EI group. There was only slight accumulation of PMNs in alveolar septa compared with plate C. Mild alveolar septal edema and moderate aggregations of PMNs are visible. The Annals of Thoracic Surgery 2007 83, 153-160DOI: (10.1016/j.athoracsur.2006.08.023) Copyright © 2007 The Society of Thoracic Surgeons Terms and Conditions