Effects of a specific neutrophil elastase inhibitor, ONO-5046, on ischemia-reperfusion injury after thoracoabdominal aortic cross-clamp in rabbits

Yoshifumi Kotake, Midori Matsumoto, Toru Kotani, Hiroshi Morisaki, Ryoichi Ochiai, Junzo Takeda

Research output: Contribution to journalArticle

Abstract

Introduction: Neutrophil activation is an important process in PMN-mediated injury including ischemia-reperfusion (I/R). We hypothesized that ONO-5046, a specific neutrophil elastase inhibitor, attenuated neutrophil activation and subsequently ameliorated organ damage during VR. In the present study, we examined the effects of ONO-5046 on neutrophil activation, liver and lung injury in a rabbit model of hepatoenteric ischemia-reperfusion. Methods: With ACUC approval, eighteen rabbits underwent 30 minutes of hepatoenteric ischemia induced by cross-clamping descending aorta and 3hr of reperfusion. These animals received ertherONO-5046 (10mg/kg bolus followed by 10mg/kg/hr infusion) or vehicle (control). Neutrophil activity was assessed by luminol-dependent chemiluminescence (CL) berore crossclamp and 3hr after reperfusion. Blood lactate, plasmaAST, LDHand protein concentration of BALF were also measured. The data obtained 3hrs after reperfusion were statistically analyzed by Mann-Whitneyt and unpaired t-test. Results: No significant differences of baseline data were observed between the groups. (#p<0.05 vs Control) Control (n=9) ONO-5046 (n=9) neutrophil CL(%change vs before) 338±128% 182±70%# blood lactate(μM) 5.8±2.4 3.5±0.8# plasma AST(U/I) 417±263 149±91# plasma LDH(U/I) 1084±656 446±133# BALF protein(mg/dl) 39.9±37.4 7.3±1.7# Conclusion: Hepatoenteric ischemia-reperfusion promoted significant activation of circulating neutrophils. ONO-5046 attenuated neutrophil activation and remote organ damage during ischemia-reperfusion.

Original languageEnglish
JournalCritical Care Medicine
Volume27
Issue number1 SUPPL.
Publication statusPublished - 1999

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Secretory Proteinase Inhibitory Proteins
Neutrophil Activation
Reperfusion Injury
Reperfusion
Rabbits
Ischemia
Luminescence
Lactic Acid
Neutrophils
Luminol
Lung Injury
Thoracic Aorta
Constriction
sivelestat
Proteins
Liver

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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Effects of a specific neutrophil elastase inhibitor, ONO-5046, on ischemia-reperfusion injury after thoracoabdominal aortic cross-clamp in rabbits. / Kotake, Yoshifumi; Matsumoto, Midori; Kotani, Toru; Morisaki, Hiroshi; Ochiai, Ryoichi; Takeda, Junzo.

In: Critical Care Medicine, Vol. 27, No. 1 SUPPL., 1999.

Research output: Contribution to journalArticle

Kotake, Yoshifumi ; Matsumoto, Midori ; Kotani, Toru ; Morisaki, Hiroshi ; Ochiai, Ryoichi ; Takeda, Junzo. / Effects of a specific neutrophil elastase inhibitor, ONO-5046, on ischemia-reperfusion injury after thoracoabdominal aortic cross-clamp in rabbits. In: Critical Care Medicine. 1999 ; Vol. 27, No. 1 SUPPL.
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abstract = "Introduction: Neutrophil activation is an important process in PMN-mediated injury including ischemia-reperfusion (I/R). We hypothesized that ONO-5046, a specific neutrophil elastase inhibitor, attenuated neutrophil activation and subsequently ameliorated organ damage during VR. In the present study, we examined the effects of ONO-5046 on neutrophil activation, liver and lung injury in a rabbit model of hepatoenteric ischemia-reperfusion. Methods: With ACUC approval, eighteen rabbits underwent 30 minutes of hepatoenteric ischemia induced by cross-clamping descending aorta and 3hr of reperfusion. These animals received ertherONO-5046 (10mg/kg bolus followed by 10mg/kg/hr infusion) or vehicle (control). Neutrophil activity was assessed by luminol-dependent chemiluminescence (CL) berore crossclamp and 3hr after reperfusion. Blood lactate, plasmaAST, LDHand protein concentration of BALF were also measured. The data obtained 3hrs after reperfusion were statistically analyzed by Mann-Whitneyt and unpaired t-test. Results: No significant differences of baseline data were observed between the groups. (#p<0.05 vs Control) Control (n=9) ONO-5046 (n=9) neutrophil CL({\%}change vs before) 338±128{\%} 182±70{\%}# blood lactate(μM) 5.8±2.4 3.5±0.8# plasma AST(U/I) 417±263 149±91# plasma LDH(U/I) 1084±656 446±133# BALF protein(mg/dl) 39.9±37.4 7.3±1.7# Conclusion: Hepatoenteric ischemia-reperfusion promoted significant activation of circulating neutrophils. ONO-5046 attenuated neutrophil activation and remote organ damage during ischemia-reperfusion.",
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T1 - Effects of a specific neutrophil elastase inhibitor, ONO-5046, on ischemia-reperfusion injury after thoracoabdominal aortic cross-clamp in rabbits

AU - Kotake, Yoshifumi

AU - Matsumoto, Midori

AU - Kotani, Toru

AU - Morisaki, Hiroshi

AU - Ochiai, Ryoichi

AU - Takeda, Junzo

PY - 1999

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N2 - Introduction: Neutrophil activation is an important process in PMN-mediated injury including ischemia-reperfusion (I/R). We hypothesized that ONO-5046, a specific neutrophil elastase inhibitor, attenuated neutrophil activation and subsequently ameliorated organ damage during VR. In the present study, we examined the effects of ONO-5046 on neutrophil activation, liver and lung injury in a rabbit model of hepatoenteric ischemia-reperfusion. Methods: With ACUC approval, eighteen rabbits underwent 30 minutes of hepatoenteric ischemia induced by cross-clamping descending aorta and 3hr of reperfusion. These animals received ertherONO-5046 (10mg/kg bolus followed by 10mg/kg/hr infusion) or vehicle (control). Neutrophil activity was assessed by luminol-dependent chemiluminescence (CL) berore crossclamp and 3hr after reperfusion. Blood lactate, plasmaAST, LDHand protein concentration of BALF were also measured. The data obtained 3hrs after reperfusion were statistically analyzed by Mann-Whitneyt and unpaired t-test. Results: No significant differences of baseline data were observed between the groups. (#p<0.05 vs Control) Control (n=9) ONO-5046 (n=9) neutrophil CL(%change vs before) 338±128% 182±70%# blood lactate(μM) 5.8±2.4 3.5±0.8# plasma AST(U/I) 417±263 149±91# plasma LDH(U/I) 1084±656 446±133# BALF protein(mg/dl) 39.9±37.4 7.3±1.7# Conclusion: Hepatoenteric ischemia-reperfusion promoted significant activation of circulating neutrophils. ONO-5046 attenuated neutrophil activation and remote organ damage during ischemia-reperfusion.

AB - Introduction: Neutrophil activation is an important process in PMN-mediated injury including ischemia-reperfusion (I/R). We hypothesized that ONO-5046, a specific neutrophil elastase inhibitor, attenuated neutrophil activation and subsequently ameliorated organ damage during VR. In the present study, we examined the effects of ONO-5046 on neutrophil activation, liver and lung injury in a rabbit model of hepatoenteric ischemia-reperfusion. Methods: With ACUC approval, eighteen rabbits underwent 30 minutes of hepatoenteric ischemia induced by cross-clamping descending aorta and 3hr of reperfusion. These animals received ertherONO-5046 (10mg/kg bolus followed by 10mg/kg/hr infusion) or vehicle (control). Neutrophil activity was assessed by luminol-dependent chemiluminescence (CL) berore crossclamp and 3hr after reperfusion. Blood lactate, plasmaAST, LDHand protein concentration of BALF were also measured. The data obtained 3hrs after reperfusion were statistically analyzed by Mann-Whitneyt and unpaired t-test. Results: No significant differences of baseline data were observed between the groups. (#p<0.05 vs Control) Control (n=9) ONO-5046 (n=9) neutrophil CL(%change vs before) 338±128% 182±70%# blood lactate(μM) 5.8±2.4 3.5±0.8# plasma AST(U/I) 417±263 149±91# plasma LDH(U/I) 1084±656 446±133# BALF protein(mg/dl) 39.9±37.4 7.3±1.7# Conclusion: Hepatoenteric ischemia-reperfusion promoted significant activation of circulating neutrophils. ONO-5046 attenuated neutrophil activation and remote organ damage during ischemia-reperfusion.

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