Addition of a neutrophil elastase inhibitor to the organ flushing solution decreases lung reperfusion injury in rat lung transplantation

Mori, Hideaki; Nagahiro, Itaru; Osaragi, Tomohiko; Kotani, Kazutoshi; Nakanishi, Hidehiro; Sano, Yoshifumi; Date, Hiroshi; Shimizu, Nobuyoshi
November 2007
European Journal of Cardio-Thoracic Surgery;Nov2007, Vol. 32 Issue 5, p791
Academic Journal
Abstract: Background: Neutrophil elastase plays an important role in ischemia–reperfusion injury. We hypothesized that the addition of sivelestat, a specific neutrophil elastase inhibitor, to the organ flushing solution would decrease reperfusion injury in a rat single left-lung transplant model. Methods: All donor lungs were flushed with 25ml low-potassium dextran–glucose solution and stored for 16h at 4°C. Rats were divided into three experimental groups (n =10) that received donor lungs washed in either normal flushing solution (group 1), or flushing solution containing 20mg sivelestat (group 2) or 40mg sivelestat (group 3). Graft function was assessed 48h after reperfusion using five measurements: isolated graft oxygenation, wet/dry ratio, peak airway pressure, tissue myeloperoxidase activity, and serum lipid peroxides level. Histological examination of lung grafts was also performed. Results: Group 3 showed better oxygenation (groups 1, 2, and 3: 133.9±113.5, 254.0±84.6, and 378.7±77.6mmHg, respectively; p <0.0001 vs group 1, p =0.0052 vs group 2), lower peak airway pressure (groups 1, 2, and 3: 28.7±6.1, 26.0±5.8, and 21.5±5.3mmHg, respectively; p =0.0385 vs group 1), lower wet/dry ratio (groups 1, 2, and 3: 6.74±0.78, 5.77±0.52, and 4.90±0.16, respectively; p =0.0010 vs group 1), and lower myeloperoxidase activity (groups 1, 2, and 3: 0.304±0.081, 0.178±0.053, and 0.106±0.029 ΔOD/mg/min, respectively; p <0.0001 vs group 1, p =0.0319 vs group 2). No significant differences in arterial PaCO2 and serum lipid peroxide levels were observed between the three groups. Conclusions: Addition of sivelestat to the organ flushing solution ameliorated ischemia–reperfusion injury in a lung transplant model.


Related Articles

  • Activation of Intracellular Neutrophil Elastase in the Transplantation of Ischemic Liver. Otsuka, M.; Takada, Y.; Fukunaga, K.; Taniguchi, H.; Todoroki, T. // European Surgical Research;2001, Vol. 33 Issue 5/6, p355 

    Ischemia-reperfusion injury is an important cause of primary nonfunction of transplanted organs, and neutrophil elastase has been implicated in the pathophysiology of ischemia-reperfusion injury. We assessed the kinetics of intracellular neutrophil elastase (INE) activity in canine liver...

  • Lung injury following acute kidney injury: kidney-lung crosstalk. Doi, Kent; Ishizu, Tomoko; Fujita, Toshiro; Noiri, Eisei // Clinical & Experimental Nephrology;Aug2011, Vol. 15 Issue 4, p464 

    The mortality of acute kidney injury (AKI) remains unacceptably high, especially associated with acute respiratory failure. Lung injury complicated with AKI was previously considered as 'uremic lung', which is characterized by volume overload and increased vascular permeability. New experimental...

  • Neutrophil Elastase Inhibitor Ameliorates Reperfusion Injury in a Canine Model of Lung Transplantation. Aoki, T.; Tsuchida, M.; Takekubo, M.; Saito, M.; Sato, K.; Hayashi, J. // European Surgical Research;Sep/Oct2005, Vol. 37 Issue 5, p274 

    Background: We investigated the effects of neutrophil elastase inhibitor ONO-5046 Na on lung ischemia-reperfusion injury in a canine model of single lung transplantation. Methods: 24 mongrel dogs, 12 donors and 12 recipients, were used for single lung transplantation. Lung grafts were preserved...

  • The presence of elafin, SLPI, IL1-RA and STNFα RI in head and neck squamous cell carcinomas and their relation to the degree of tumour differentiation. Westin, U.; Nyström, M.; Ljungcrantz, I.; Eriksson, B.; Ohlsson, K. // Mediators of Inflammation;Feb2002, Vol. 11 Issue 1, p7 

    Biopsy samples of head and neck carcinomas were investigated with regard to elafin, secretory leukocyte protease inhibitor (SLPI), interleukin 1-receptor antagonist [(IL)1-RA] and soluble tumour necrosis factor α receptor antagonist (STNFα RI). SLPI and elafin are serine protease...

  • Diagnostic potential of neutrophil elastase inhibitor complex in the routine care of critically ill newborn infants. Fischer, Joachim E.; Brunner, Anna; Janousek, Martin; Nadal, David; Blau, Nenad; Fanconi, Sergio; Fischer, J E; Brunner, A; Janousek, M; Nadal, D; Blau, N; Fanconi, S // European Journal of Pediatrics;2000, Vol. 159 Issue 9, p659 

    Unlabelled: It has been suggested that determination of the neutrophil elastase alpha1-proteinase inhibitor complex (E-alpha1PI) improves the diagnosis of bacterial infection in newborns. We evaluated the use of E-alpha1PI measurements in 143 newborns, consecutively admitted to a...

  • Green tea polyphenol extract attenuates ischemia/reperfusion injury of the gut. Muià, Carmelo; Mazzon, Emanuela; Di Paola, Rosanna; Genovese, Tiziana; Menegazzi, Marta; Caputi, Achille P.; Suzuki, Hisanori; Cuzzocrea, Salvatore // Naunyn-Schmiedeberg's Archives of Pharmacology;May2005, Vol. 371 Issue 5, p364 

    Various studies have clearly demonstrated that green tea catechins possess potent antioxidative properties, and the preventive effects against various oxidative diseases have been reported. The aim of this study was to investigate the effect of green tea extract on the tissue injury caused by...

  • Plasma and urine leukocyte elastase–α1protease inhibitor complex as a marker of early and long-term kidney graft function. Zynek-Litwin, Małgorzata; Kuźniar, Jakub; Marchewka, Zofia; Kopeć, Wacław; Kusztal, Mariusz; Patrzałek, Dariusz; Biecek, Przemysław; Klinger, Marian // Nephrology Dialysis Transplantation;Jul2010, Vol. 25 Issue 7, p2346 

    Background. Neutrophils are mediators of ischaemia/reperfusion (I/R) injury following kidney transplantation (kTx). Leukocyte elastase (LE) complex with α1protease inhibitor (LE–α1PI) is a marker of neutrophil degranulation. The aim of this study was to evaluate LE–α1PI as...

  • Acute limb ischaemia. Callum, Ken; Bradbury, Andrew // BMJ: British Medical Journal (International Edition);03/18/2000, Vol. 320 Issue 7237, p764 

    Provides information on the classification of acute limb ischaemia. Clinical features and aetiology of acute limb ischaemia; General measures for acute limb ischaemia; Details on reperfusion syndrome.

  • CORRIGENDUM: Novel n-3 Immunoresolvents: Structures and Actions. Dalli, Jesmond; Colas, Romain A.; Serhan, Charles N. // Scientific Reports;10/24/2014, p1 

    A correction to the article "Novel n-3 Immunoresolvents: Structures and Actions" by Jesmond Dalli, Romain A. Colas and Charles N. Serhan is presented.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics