Neutrophil elastase inhibitor improves survival rate after ischemia reperfusion injury caused by supravisceral aortic clamping in rats.

Abstract

BACKGROUND:

Sivelestat sodium hydrate is a specific neutrophil elastase inhibitor effective in acute lung injury (ALI) associated with systemic inflammatory response syndrome. Bowel ischemia reperfusion injury (IRI) induced by supravisceral aortic clamping is associated with an excessive systemic inflammatory response, resulting in remote organ damage, including ALI. In this study, we investigated whether sivelestat can attenuate neutrophil sequestration in the lung, alleviate ALI, and improve survival in a rat bowel IRI model.

METHODS:

Adult male Sprague-Dawley rats underwent bowel IRI induced by supravisceral aortic clamping and were randomly assigned to receive sivelestat or saline (control) and monitored for survival. We randomly assigned other rats to undergo laparotomy alone (sham operation), IRI alone, or IRI and sivelestat treatment. We evaluated blood samples for organ function, cytokine levels, and neutrophil elastase activity after reperfusion. Organs were analyzed histologically. We also determined lung injury in another set of rats.

RESULTS:

Bowel IRI induced a significant increase in serum variables indicative of organ function, cytokine concentrations, neutrophil elastase activity, and lung permeability and edema, which reflected the presence of both systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome. Treatment with sivelestat significantly improved survival rate, lung permeability and edema, and significantly decreased levels of creatinine, interleukin 6, interleukin 10, and neutrophil elastase activity. Histological studies showed that sivelestat-treated rats had less bowel IRI-induced damage to lung and liver tissue than controls.

CONCLUSION:

In a rat model, administration of sivelestat attenuated the effects of bowel IRI induced by supravisceral aortic clamping, and improved the survival rate.

• Authors: Naoki Fujimura, Hideaki Obara, Koichi Suda, Hiroya Takeuchi, Taku Miyasho, Kazufumi Kawasako, Wenlin Du, Shingo Yamada, Shigeshi Ono, Kenji Matsumoto, Sachiko Matsuda, Hiroshi Yagi, Minoru Kitago, Masahiro Shinoda, Osamu Itano, Minoru Tanabe, Michiie Sakamoto, Ikuro Maruyama, Yuko Kitagawa
• Journal: The Journal of surgical research (J Surg Res) Vol. 180 Issue 1 Pg. e31-6 (Mar 2013) ISSN: 1095-8673 [Electronic] United States
• PMID: 22595015 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Proteinase Inhibitory Proteins, Secretory
• Serine Proteinase Inhibitors
• Sulfonamides
• sivelestat
• Glycine

Topics

• Animals
• Aorta, Abdominal (surgery)
• Aortic Aneurysm, Abdominal (surgery)
• Constriction
• Glycine (analogs & derivatives, therapeutic use)
• Intestines (blood supply)
• Male
• Proteinase Inhibitory Proteins, Secretory (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, mortality, pathology)
• Serine Proteinase Inhibitors (therapeutic use)
• Sulfonamides (therapeutic use)
• Survival Rate