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

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, Yuukou Kitagawa

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
JournalJournal of Surgical Research
Volume180
Issue number1
DOIs
Publication statusPublished - 2013 Mar

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Secretory Proteinase Inhibitory Proteins
Reperfusion Injury
Constriction
Leukocyte Elastase
Acute Lung Injury
Systemic Inflammatory Response Syndrome
Lung
Permeability
Edema
Cytokines
Lung Injury
sivelestat
Interleukin-10
Laparotomy
Reperfusion
Sprague Dawley Rats
Interleukin-6
Creatinine
Neutrophils
Anti-Inflammatory Agents

Keywords

  • Abdominal aortic aneurysm
  • Acute lung injury
  • Ischemia reperfusion injury
  • Neutrophil elastase inhibitor
  • Supravisceral aortic clamping
  • Systemic inflammatory response syndrome

ASJC Scopus subject areas

  • Surgery

Cite this

Neutrophil elastase inhibitor improves survival rate after ischemia reperfusion injury caused by supravisceral aortic clamping in rats. / Fujimura, Naoki; Obara, Hideaki; Suda, Koichi; Takeuchi, Hiroya; Miyasho, Taku; Kawasako, Kazufumi; Du, Wenlin; Yamada, Shingo; Ono, Shigeshi; Matsumoto, Kenji; Matsuda, Sachiko; Yagi, Hiroshi; Kitago, Minoru; Shinoda, Masahiro; Itano, Osamu; Tanabe, Minoru; Sakamoto, Michiie; Maruyama, Ikuro; Kitagawa, Yuukou.

In: Journal of Surgical Research, Vol. 180, No. 1, 03.2013.

Research output: Contribution to journalArticle

Fujimura, Naoki ; Obara, Hideaki ; Suda, Koichi ; Takeuchi, Hiroya ; Miyasho, Taku ; Kawasako, Kazufumi ; Du, Wenlin ; Yamada, Shingo ; Ono, Shigeshi ; Matsumoto, Kenji ; Matsuda, Sachiko ; Yagi, Hiroshi ; Kitago, Minoru ; Shinoda, Masahiro ; Itano, Osamu ; Tanabe, Minoru ; Sakamoto, Michiie ; Maruyama, Ikuro ; Kitagawa, Yuukou. / Neutrophil elastase inhibitor improves survival rate after ischemia reperfusion injury caused by supravisceral aortic clamping in rats. In: Journal of Surgical Research. 2013 ; Vol. 180, No. 1.
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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.",
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AU - Fujimura, Naoki

AU - Obara, Hideaki

AU - Suda, Koichi

AU - Takeuchi, Hiroya

AU - Miyasho, Taku

AU - Kawasako, Kazufumi

AU - Du, Wenlin

AU - Yamada, Shingo

AU - Ono, Shigeshi

AU - Matsumoto, Kenji

AU - Matsuda, Sachiko

AU - Yagi, Hiroshi

AU - Kitago, Minoru

AU - Shinoda, Masahiro

AU - Itano, Osamu

AU - Tanabe, Minoru

AU - Sakamoto, Michiie

AU - Maruyama, Ikuro

AU - Kitagawa, Yuukou

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AB - 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.

KW - Abdominal aortic aneurysm

KW - Acute lung injury

KW - Ischemia reperfusion injury

KW - Neutrophil elastase inhibitor

KW - Supravisceral aortic clamping

KW - Systemic inflammatory response syndrome

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