Abstract
We tested the effect of Ono-EI-600, an elastase inhibitor that suppresses cytokine release, on ventilator-induced lung injury in a rat model. After Wistar rats (aged 8–11 weeks) were anesthetized and tracheostomized, they were randomly assigned to four groups: high tidal volume (VT) group (H group: n = 10) receiving peak inspiratory pressure (PIP) 30 cmH2O for 240 min; high VT with drug group (HD group: n = 10) receiving the same ventilation settings as H group and also intravenous infusion 10 mg·kg−1·h−1 of Ono-EI-600 during the protocol; the lower VT group (L group: n = 5) receiving PIP 10 cmH2O for 240 min; and control group (C group: n = 5) receiving the same ventilation as L group for 30 min. The cytokine levels (IL-6 and CINC-1) in the bronchoalveolar lavage fluid (BALF) of the H group were significantly higher than those of the C and L groups (P < 0.05). However, for the H and HD groups, no differences were found in arterial blood gas data, cytokine levels in BALF, and histological injury scores. Our experiment provided no evidence that elastase inhibitor Ono-EI-600 protects against lung injury induced by high VT ventilation.
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References
InstitutionalAuthorNameThe acute respiratory distress syndrome network (2000) ArticleTitleVentilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome N Engl J Med 342 1301–1308 Occurrence Handle10.1056/NEJM200005043421801
RG Brower GD Rubenfeld (2003) ArticleTitleLung-protective ventilation strategies in acute lung injury Crit Care Med 31 S312–S316 Occurrence Handle12682458
Z Fu ML Costello K Tsukimoto R Prediletto AR Elliott O Mathieu-Costello JB West (1992) ArticleTitleHigh lung volume increases stress failure in pulmonary capillaries J Appl Physiol 73 123–133 Occurrence Handle1:STN:280:By2A2s3lsFE%3D Occurrence Handle1506359
AN von Bethmann F Brasch R Nusing K Vogt HD Volk KM Muller A Wendel S Uhlig (1998) ArticleTitleHyperventilation induces release of cytokines from perfused mouse lung Am J Respir Crit Care Med 157 263–272 Occurrence Handle1:STN:280:DyaK1c7gs1SrtA%3D%3D Occurrence Handle9445308
JD Ricard D Dreyfuss G Saumon (2001) ArticleTitleProduction of inflammatory cytokines in ventilator-induced lung injury: a reappraisal Am J Respir Crit Care Med 163 1176–1180 Occurrence Handle1:STN:280:DC%2BD3MzisFGrug%3D%3D Occurrence Handle11316656
D Dreyfuss JD Ricard G Saumon (2003) ArticleTitleOn the physiologic and clinical relevance of lung-borne cytokines during ventilator-induced lung injury Am J Respir Crit Care Med 167 1467–1471 Occurrence Handle10.1164/rccm.200206-611CP Occurrence Handle12770853
SW Woo J Hedley-Whyte (1972) ArticleTitleMacrophage accumulation and pulmonary edema due to thoracotomy and lung overinflation J Appl Physiol 33 14–21 Occurrence Handle1:STN:280:CS2B3MrisVQ%3D Occurrence Handle5037402
JA Belperio MP Keane MD Burdick V Londhe YY Xue K Li RJ Phillips RM Strieter (2002) ArticleTitleCritical role for CXCR2 and CXCR2 ligands during the pathogenisis of ventilator-induced lung injury J Clin Invest 110 1703–1716 Occurrence Handle10.1172/JCI200215849 Occurrence Handle1:CAS:528:DC%2BD38Xptlars7s%3D Occurrence Handle12464676
LB Ware MA Matthay (2000) ArticleTitleThe acute respiratory distress syndrome N Engl J Med 342 1334–1349 Occurrence Handle10.1056/NEJM200005043421806 Occurrence Handle1:STN:280:DC%2BD3c3jvFGhsw%3D%3D Occurrence Handle10793167
WL Lee GP Downey (2001) ArticleTitleLeukocyte elastase. Physiological functions and role in acute lung injury Am J Respir Crit Care Med 164 896–904 Occurrence Handle1:STN:280:DC%2BD3MvpvF2lsA%3D%3D Occurrence Handle11549552
BG Zeiher S Matsuoka K Kawabata JE Repine (2002) ArticleTitleNeutrophil elastase and acute lung injury: Prospects for sivelestat and other neutrophil elastase inhibitors as therapeutics Crit Care Med 30 S281–S287 Occurrence Handle1:CAS:528:DC%2BD38Xktlykt7g%3D Occurrence Handle12004249
K Kawabata T Hagio S Matsuoka (2002) ArticleTitleThe role of neutrophil elastase in acute lung injury Eur J Pharmacol 451 1–10 Occurrence Handle10.1016/S0014-2999(02)02182-9 Occurrence Handle1:CAS:528:DC%2BD38XmvVCrs7g%3D Occurrence Handle12223222
K Kubo T Kobayashi T Hayano T Koizumi T Honda M Sekiguchi A Sakai (1994) ArticleTitleEffects of ONO-5046, a specific neutrophil elastase inhibitor, on endotoxin-induced lung injury in sheep J Appl Physiol 77 1333–1340 Occurrence Handle1:CAS:528:DyaK2cXmslOrtbw%3D Occurrence Handle7836137
K Nishina K Mikawa Y Takao N Maekawa M Shiga H Obara (1997) ArticleTitleONO-5046, an elastase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits Anesth Analg 84 1097–1103 Occurrence Handle1:CAS:528:DyaK2sXjtlKmsLg%3D Occurrence Handle9141938
Y Miyazaki T Inoue M Kyi M Sawada S Miyake Y Yoshizawa (1998) ArticleTitleEffects of a neutrophil elastase inhibitor (ONO-5046) on acute pulmonary injury induced by tumor necrosis factor alpha (TNFα) and activated neutrophils in isolated perfused rabbit lungs Am J Respir Crit Care Med 157 89–94 Occurrence Handle1:STN:280:DyaK1c7gs1Slsw%3D%3D Occurrence Handle9445283
N Tomizawa S Ohwada T Ohya I Takeyoshi T Ogawa Y Kawashima M Adachi Y Morishita (1999) ArticleTitleThe effects of a neutrophil elastase inhibitor (ONO-5046·Na) and neutrophil depletion using a granulotrap (G-1) column on lung reperfusion injury in dogs J Heart Lung Transplant 18 637–645 Occurrence Handle1:STN:280:DyaK1MznvFCjug%3D%3D Occurrence Handle10452339
M Takayama M Ishibashi H Ishii T Kuraki T Nishida M Yoshida (2001) ArticleTitleEffects of neutrophil elastase inhibitor (ONO-5046) on lung injury after intestinal ischemia-reperfusion J Appl Physiol 91 1800–1807 Occurrence Handle1:CAS:528:DC%2BD3MXnsFSlsL4%3D Occurrence Handle11568165
BG Zeiher A Artigas JL Vincent A Dmitrienko K Jackson BT Thompson G Bernard InstitutionalAuthorNamefor the STRIVE study group (2004) ArticleTitleNeutrophil elastase inhibition in acute lung injury: results of the STRIVE study Crit Care Med 32 1695–1702 Occurrence Handle1:CAS:528:DC%2BD2cXmtFCgtLs%3D Occurrence Handle15286546
H Imanaka M Shimaoka N Matsuura M Nishimura N Ohta H Kiyono (2001) ArticleTitleVentilator-induced lung injury is associtated with neutrophil infiltration, macrophage activation, and TGF-β1 mRNA upregulation in rat lungs Anesth Analg 92 428–436 Occurrence Handle1:CAS:528:DC%2BD3MXht1Sqtr8%3D Occurrence Handle11159246
JC Parker LA Hernandez KJ Peevy (1993) ArticleTitleMechanisms of ventilator-induced lung injury Crit Care Med 21 131–143 Occurrence Handle1:STN:280:ByyC3s%2Fmt1I%3D Occurrence Handle8420720
D Dreyfuss G Saumon (1998) ArticleTitleVentilator-induced lung injury. Lessons from experimental studies Am J Respir Crit Care Med 157 294–323 Occurrence Handle1:STN:280:DyaK1c7gs1SqsA%3D%3D Occurrence Handle9445314
J Pugin I Dunn P Jolliet D Tassaux JL Magnenat LP Nicod JC Chevrolet (1998) ArticleTitleActivation of human macrophages by mechanical ventilation in vitro Am J Physiol 275 L1040–L1050 Occurrence Handle1:CAS:528:DyaK1MXhs1Sktw%3D%3D Occurrence Handle9843840
NE Vlahakis MA Schroeder AH Limper RD Hubmayr (1999) ArticleTitleStretch induces cytokine release by alveolar epithelial cells in vitro Am J Physiol 277 L167–L173 Occurrence Handle1:CAS:528:DyaK1MXkslKnt7c%3D Occurrence Handle10409244
VM Ranieri PM Suter C Tortorella R De Tullio JM Dayer A Brienza F Bruno AS Slutsky (1999) ArticleTitleEffect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome. A randomized controlled trial JAMA 282 54–61 Occurrence Handle10.1001/jama.282.1.54 Occurrence Handle1:STN:280:DyaK1MzjtFOqug%3D%3D Occurrence Handle10404912
S Tamakuma M Ogawa N Aikawa T Kubota H Hirasawa A Ishizaka N Taenaka C Hamada S Matsuoka T Abiru (2004) ArticleTitleRelationship between neutrophil elastase and acute lung injury in humans Pulm Pharmacol Ther 17 271–279 Occurrence Handle1:CAS:528:DC%2BD2cXotlSlurc%3D Occurrence Handle15477122
S Takeda A Ishizaka Y Fujino T Fukuoka O Nagano Y Yamada J Takezawa InstitutionalAuthorNameMulticenter Clinical Trial Committee, Japan Society of Respiratory Care Medicine (2005) ArticleTitleTime to change diagnostic criteria of ARDS: toward the disease entity-based subgrouping Pulm Pharmacol Ther 18 115–119 Occurrence Handle1:CAS:528:DC%2BD2MXis1SltA%3D%3D Occurrence Handle15712404
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Fujita, Y., Fujino, Y., Maeda, Y. et al. Effect of Ono-EI-600 elastase inhibitor on high-tidal-volume-induced lung injury in rats. J Anesth 20, 141–144 (2006). https://doi.org/10.1007/s00540-005-0369-2
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DOI: https://doi.org/10.1007/s00540-005-0369-2