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Ann Thorac Surg 2007;83:153-160
© 2007 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

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

First Department of Surgery, Hirosaki University School of Medicine, Aomori, Japan

Accepted for publication August 8, 2006.

* Address correspondence to Dr Fukuda, First Department of Surgery, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 36-8562 Japan. (Email: ikuofuku{at}cc.hirosaki-u.ac.jp).

BACKGROUND: Neutrophil elastase probably contributes to the development of acute lung injury after cardiopulmonary bypass (CPB) in patients with infection or shock. We evaluated whether pretreatment with sivelestat sodium hydrate, a neutrophil elastase inhibitor (EI), can prevent acute lung injury caused by CPB.

METHODS: Rabbits were assigned four groups: CPB for 60 minutes, control CPB group; low-dose lipopolysaccharide (LPS) administration without CPB, LPS group; CPB after lipopolysaccharide administration, LPS+CPB group; or preparation with continuous infusion of sivelestat and CPBs after lipopolysaccharide administration, EI group. Blood samples to determine blood gas concentration, plasma elastase activity, and plasma interleukin-8 levels were obtained. Histopathologic examinations of the lung were performed.

RESULTS: The decreased arterial oxygen pressure at the end of CPB was observed in the LPS+CPB group only, but was suppressed in the EI group (p < 0.01). Elastase activity was markedly elevated at 120 minutes after CPB, and interleukin-8 levels were markedly elevated at 180 minutes in the LPS+CPB group but were much lower (p < 0.05) in the EI group. Histopathology demonstrated accumulation of polymorphonuclear neutrophils in bronchoalveolar areas in the LPS+CPB group (p < 0.01). Pulmonary myeloperoxidase activity was significantly lower in the LPS+CPB group than in the other groups (p < 0.01). These changes were minimal in the EI group.

CONCLUSIONS: The combination of low dose LPS+60 minutes of CPB, but neither intervention alone, produced evidence of acute lung injury in a rabbit model. This did not occur when the animals were pretreated with sivelestat.




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