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Thorac Cardiovasc Surg 2010; 58(3): 164-168
DOI: 10.1055/s-0029-1240846
Original Cardiovascular

© Georg Thieme Verlag KG Stuttgart · New York

Efficacy of Neutrophil Elastase Inhibitor on Type A Acute Aortic Dissection

T. Niino1 , M. Hata1 , A. Sezai1 , I. Yoshitake1 , S. Unosawa1 , K. Fujita1 , K. Shimura1 , S. Osaka1 , K. Minami1
  • 1Department of Cardiovascular Surgery, Nihon University School of Medicine, Tokyo, Japan
Further Information

Publication History

received Sept. 1, 2009

Publication Date:
07 April 2010 (online)

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Abstract

Background: Surgery for type A acute aortic dissection (AAD) is associated with a high mortality and incidence of postoperative complications, including acute respiratory failure and coagulopathy. Aim of the study was to investigate the effects of sivelestat on pulmonary function and coagulopathy in patients undergoing surgery for AAD. Methods: Sixty patients undergoing emergency ascending replacement for AAD were divided into two groups. Group I was administered sivelestat intravenously from the beginning of surgery until extubation. Group II was not treated with sivelestat. The platelet count, antithrombin III (AT III) level, leukocyte count, C-reactive protein (CRP) level, prothrombin time (PT), activated partial thrombin time (APTT), and prothrombin time-international normalized ratio (PT‐INR) were measured. Results: The postoperative decrease of AT III and the platelet count on admission to the intensive care unit (ICU) and 3 hours later were significantly less in group I. The leukocyte count and the values of CRP, PT, APTT, and PT‐INR did not differ significantly between the groups. The duration of mechanical ventilation after surgery tended to be shorter in group I. Conclusions: Sivelestat significantly reduced the postoperative decreases in AT III and platelet count in patients undergoing emergency surgery for AAD.

Key words

aortic disease - cardiovascular surgery - thoracic surgery

References

  • 1 Ehrlich E P, Ergin A, McCullough J N et al. Results of immediate surgical treatment of all acute type A dissections.  Circulation. 2000;  102 (Suppl. III) 248-252
    PubMedSearch in Google Scholar
  • 2 Knipp B S, Deep G M, Prager R L, Williams C Y, Upchurch Jr G R, Patel H J. A contemporary analysis of outcomes for operative repair of type A aortic dissection in the United States.  Surgery. 2007;  142 524-528
    CrossrefPubMedSearch in Google Scholar
  • 3 Baue A E. Cardiopulmonary bypass for cardiac surgery: an inflammatory event: can it be modulated?. Baue AE, Faist E, Fry DE Multiple organ failure: pathophysiology, prevention, and therapy. New York; Springer Verlag 2000: 82-85
    PubMedSearch in Google Scholar
  • 4 Siecinski R, Szlam F, Chen E P, Bader S O, Levy J H, Tanaka K A. Antithrombin deficiency increases thrombin activity after prolonged cardiopulmonary bypass.  Anesth Analg. 2008;  106 713-718
    CrossrefPubMedSearch in Google Scholar
  • 5 Hata M, Suzuki M, Sezai A et al. Should emergency surgical intervention be performed for octogenarian with type A acute aortic dissection?.  J Thorac Cardiovascu Surg. 2008;  135 1042-1046
    PubMedSearch in Google Scholar
  • 6 De Backer W A, Amsel B, Jorens P G et al. N-acetyl-cysteine pretreatment of cardiac surgery patients influences plasma neutrophil elastase and neutrophil influx in bronchoalveolar lavage fluid.  Intensive Care Med. 1996;  22 900-908
    CrossrefPubMedSearch in Google Scholar
  • 7 Chollet-Martin S, Jourdain B, Gibert C, Elbim C, Chastre J, Gougerot-Pocidalo M A. Interactions between neutrophils and cytokines in blood and alveolar spaces during ARDS.  Am J Respir Crit Care Med. 1996;  153 594-601
    PubMedSearch in Google Scholar
  • 8 Donnelly S C, Strieter R M, Kunkel S L et al. Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups.  Lancet. 1993;  341 643-647
    CrossrefPubMedSearch in Google Scholar
  • 9 Nakamura H, Yoshimura K, McElvaney N G, Crystat R G. Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line.  J Clin Invest. 1992;  89 1478-1484
    CrossrefPubMedSearch in Google Scholar
  • 10 Abraham E. Neutrophils and acute lung injury.  Crit Care Med. 2003;  31 (Suppl.) S195-S199
    CrossrefPubMedSearch in Google Scholar
  • 11 Kawabata K, Hagio T, Matsumoto S et al. Delayed neutrophil elastase inhibition prevents subsequent progression of acute lung injury induced by endotoxin inhalation in hamsters.  Am J Respir Crit Care Med. 2000;  161 2013-2018
    PubMedSearch in Google Scholar
  • 12 Topham M K, Carveth H J, McIntyre T M, Prescott S M, Zimmerman G A. Human endothelial cells regulate polymorphonuclear leukocyte degranulation.  FASEB J. 1998;  12 733-746
    PubMedSearch in Google Scholar
  • 13 Rainger G E, Rowley A F, Nash G B. Adhesion-dependent release of elastase from human neutrophils in a novel, flow-based model: specificity of different chemotactic agents.  Blood. 1998;  92 4819-4827
    PubMedSearch in Google Scholar
  • 14 Houston D S, Carson C W, Esmon C T. Endothelial cells and extracellular calmodulin inhibit monocyte tumor necrosis factor release and augment neutrophil elastase release.  J Biol Chem. 1997;  272 11778-11785
    CrossrefPubMedSearch in Google Scholar
  • 15 Downey G P, Dong Q, Kruger J, Dedhar S, Cherapanov V. Regulation of neutrophil activation in acute lung injury.  Chest. 1999;  116 (Suppl. 1) 46-54
    CrossrefPubMedSearch in Google Scholar
  • 16 McElvaney N G, Nakamura H, Birrer P et al. Modulation of airway inflammation in cystic fibrosis. In vivo suppression of interleukin-8 levels on the respiratory epithelial surface by aerosolization of recombinat secretory leukoprotease inhibitor.  J Clin Invest. 1992;  90 1296-1301
    CrossrefPubMedSearch in Google Scholar
  • 17 Kaneko K, Kudoh I, Hattori S et al. Neutrophil elastase inhibitor, ONO-5046, modulates acid-induced lung and systemic injury in rabbits.  Anesthesiology. 1997;  87 635-641
    CrossrefPubMedSearch in Google Scholar
  • 18 Hudson L, Milberg J, Anardi D, Maunder R J. Clinical risks for development of the acute respiratory distress syndrome.  Am J Respir Crit Care Med. 1995;  151 293-301
    CrossrefPubMedSearch in Google Scholar
  • 19 Tönz M, Mihaljevic T, von Segesser L K, Fehr J, Schmid E R, Turina M I. Acute lung injury during cardiopulmonary bypass. Are the neutrophils responsible?.  Chest. 1995;  108 1551-1556
    CrossrefPubMedSearch in Google Scholar
  • 20 Kawabata K, Hagio T, Matsumoto S et al. Delayed neutrophil elastase inhibition prevents subsequent progression of acute lung injury induced by endotoxin inhalation in hamsters.  Am J Respir Crit Care Med. 2000;  161 2013-2018
    PubMedSearch in Google Scholar
  • 21 Kadoi Y, Hinohara H, Kunimoto F et al. Pilot study of the effects of ONO-5046 in patients with acute respiratory distress syndrome.  Anesth Analg. 2004;  99 872-877
    CrossrefPubMedSearch in Google Scholar
  • 22 Tamakuma S, Ogawa M, Aikawa N et al. Relationship between neutrophil elastase and acute lung injury in humans.  Pulm Pharmacol Ther. 2004;  17 271-279
    CrossrefPubMedSearch in Google Scholar
  • 23 Yamazaki T, Ooshima H, Usui A, Watanabe T, Yasuura K. Protective effects of ONO-5046-Na, a specific neutrophil elastase inhibitor, on postperfusion lung injury.  Ann Thorac Surg. 1999;  68 2141-2146
    CrossrefPubMedSearch in Google Scholar
  • 24 Havemann K, Gramse M. Physiology and pathophysiology of neutral proteinases of human granulocytes.  Adv Exper Med Biol. 1984;  167 1-20
    PubMedSearch in Google Scholar
  • 25 Jochum M, Lander S, Heimburger N, Fritz H. Effect of human granulocytic elastase on human antithrombin III.  Hoppe-Seylers Z Physiol Chem. 1981;  362 103-112
    CrossrefPubMedSearch in Google Scholar
  • 26 Jordan R E, Nelson R M, Kilpatrick J, Newgren J O, Esmon P C, Fournel M A. Inactivation of human antithrombin by neutrophil elastase.  J Biol Chem. 1989;  264 10493-10500
    PubMedSearch in Google Scholar
  • 27 Pratt C W, Tobin R B, Church F C. Interaction of heparin cofactor II with neutrophil elastase and cathepsin G.  J Biol Chem. 1990;  265 6092-6097
    PubMedSearch in Google Scholar
  • 28 Hashimoto K, Miyamoto H, Suzuki K et al. Evidence of organ damage after cardiopulmonary bypass. The role of elastase and vasoactive mediators.  J Thorac Cardiovasc Surg. 1992;  104 666-673
    PubMedSearch in Google Scholar

Dr. Tetsuya Niino

Department of Cardiovascular Surgery
Nihon University School of Medicine

30-1 Oyaguchi Kamimachi, Itabashi-ku

173-8610 Tokyo

Japan

Phone: + 81 3 39 72 81 11

Fax: + 81 3 39 55 98 18

Email: tenino@med.nihon-u.ac.jp