Skip to main content

Advertisement

SpringerLink
Log in

Effects of a protease inhibitor, ulinastatin, on coagulation and fibrinolysis in abdominal surgery

  • Published:
Journal of Anesthesia Aims and scope Submit manuscript

Abstract

Purpose

Ulinastatin is well known to inhibit the activity of polymorphonuclear leukocyte elastase (PMNE). The PMNE concentration correlates with the activities of coagulation and fibrinolysis. The purpose of the present study was to investigate the effects of ulinastatin, a protease inhibitor, on coagulation and fibrinolysis in abdominal surgery.

Methods

Thirty patients, aged 40 to 70 years, with American Society of Anesthesiologists (ASA) physical status I or II, scheduled for major abdominal surgery, were enrolled. Anesthesia was induced with midazolam and thiopental, and was maintained with sevoflurane, nitrous oxide in oxygen, and an epidural block. An infusion of ulinastatin, 6000 units·kg−1 in 30 min, was started 1 h after the start of surgery in the ulinastatin group (15 patients). In the control group (15 patients), no protease inhibitors were infused. White blood cell count; platelet count; prothrombin time; activated partial thromboplastin time; and plasma concentrations of PMNE, antithrombin (AT), fibrin/fibrinogen degradation product (FDP), fibrinogen, plasminogen, plasmin-α2 plasmin inhibitor complex (PIC), and thrombin-antithrombin complex (TAT) were measured before, at the end of, and 12 h after surgery.

Results

TAT, PIC, and FDP after surgery were significantly lower in the ulinastatin group than in the control group. AT was decreased in the control group but not in the ulinastatin group, with significant differences between the two groups.

Conclusion

Ulinastatin could inhibit coagulation and fibrinolysis in abdominal surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. T Nishiyama A Hirasaki (1994) ArticleTitleEffect of ulinastatin on the elastase release in multiple injuries Anesth Res 30 77–80

    Google Scholar 

  2. T Nishiyama K Hanaoka (2001) ArticleTitleDo the effects of a protease inhibitor, ulinastatin, on elastase release by blood transfusion depend on interleukin 6? Crit Care Med 29 2106–2110 Occurrence Handle11700404 Occurrence Handle1:CAS:528:DC%2BD3MXptVKrsrw%3D Occurrence Handle10.1097/00003246-200111000-00010

    Article  PubMed  CAS  Google Scholar 

  3. S Aosasa S Ono H Mochizuki H Tsujimoto C Ueno A Matsumoto (2001) ArticleTitleMechanism of the inhibitory effect of protease inhibitor on tumor necrosis factor α production of monocytes Shock 15 101–105 Occurrence Handle11220636 Occurrence Handle1:STN:280:DC%2BD3M3isVamuw%3D%3D Occurrence Handle10.1097/00024382-200115020-00004

    Article  PubMed  CAS  Google Scholar 

  4. Y Sato S Ishikawa A Otaki T Takahashi Y Hasegawa M Suzuki T Yamagishi Y Mirishita (2000) ArticleTitleInduction of acute-phase reactive substances during open-heart surgery and efficacy of ulinastatin. Inhibiting cytokines and postoperative organ injury Jpn J Thorac Cardiovasc Surg 48 428–434 Occurrence Handle10965615 Occurrence Handle1:STN:280:DC%2BD3cvpsVamsQ%3D%3D

    PubMed  CAS  Google Scholar 

  5. Y Yamaguchi H Ohshiro Y Nagao K Odawara K Okabe H Hidaka K Ishihara S Uchino T Furuhashi S Yamada K Mori M Ogawa (2000) ArticleTitleUrinary trypsin inhibitor reduces C⎓X⎓C chemokine production in rat liver ischemia/reperfusion J Surg Res 94 107–115 Occurrence Handle11104650 Occurrence Handle1:CAS:528:DC%2BD3cXosVOmtLk%3D Occurrence Handle10.1006/jsre.2000.5999

    Article  PubMed  CAS  Google Scholar 

  6. ZL Cao Y Okazaki K Naito T Ueno M Natsuaki T Itoh (2000) ArticleTitleUlinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart Ann Thorac Surg 69 1121–1126 Occurrence Handle10800804 Occurrence Handle1:STN:280:DC%2BD3c3lvVOnsA%3D%3D Occurrence Handle10.1016/S0003-4975(99)01433-2

    Article  PubMed  CAS  Google Scholar 

  7. T Nishiyama T Yokoyama K Hanaoka (1996) ArticleTitleCorrelations between plasma levels of polymorphonuclear leukocyte elastase and coagulation and fibrinolysis parameters in patients undergoing major abdominal surgery Anesth Res 32 369–372

    Google Scholar 

  8. M Kopec K Bykowska S Lopaciuk M Jelenska J Kaczanowska I Sopata E Wojtecka (1980) ArticleTitleEffects of neutral proteases from human leukocytes on structure and biological properties of human factor VIII Thromb Haemost 43 211–217 Occurrence Handle6256922 Occurrence Handle1:CAS:528:DyaL3cXmtFyks7c%3D

    PubMed  CAS  Google Scholar 

  9. T Kawamura K Inada O Kimura N Akasaka R Wakusawa (1994) ArticleTitleThe inhibitory effects of ulinastatin on the increase of interleukin 8 and 6 during open heart surgery Masui (Jpn J Anesthesiol) 43 1818–1823 Occurrence Handle1:STN:280:ByqC3sbitVI%3D

    CAS  Google Scholar 

  10. H Pelzer A Schwarz N Heimburger (1988) ArticleTitleDetermination of human thrombin-antithrombin III complex in plasma with an enzyme-linked immunosorbent assay Thromb Haemost 59 101–106 Occurrence Handle3363526 Occurrence Handle1:STN:280:BieB3crisFM%3D

    PubMed  CAS  Google Scholar 

  11. T Yoshikawa M Murakami O Seto S Sugino M Kondo (1987) ArticleTitlePrevention of endotoxin-induced disseminated intravascular coagulation, and inhibition of endotoxin-induced release of thromboplastin activity from leukocytes by a protease-inhibitor, ulinastatin (in Japanese with English abstract) Masui (Jpn J Anesthesiol) 36 1281–1285 Occurrence Handle1:STN:280:BieC3MbltVU%3D

    CAS  Google Scholar 

  12. T Nishiyama K Sato H Konishi K Seto (1991) ArticleTitleChanges in polymorphonuclear leukocyte elastase activity and other parameters in response to surgical invasion (in Japanese with English abstract) ICU to CCU (Jpn J Int Care Med) 15 1055–1061

    Google Scholar 

  13. DH Perlmutter JA Pierce (1989) ArticleTitleThe α1-antitrypsin gene and emphysema Am J Physiol 257 L147–162 Occurrence Handle2679136 Occurrence Handle1:CAS:528:DyaL1MXmt12rtb0%3D

    PubMed  CAS  Google Scholar 

  14. MJ Banda AG Rice GL Griffin RM Senior (1988) ArticleTitleThe inhibitory complex of human α1-proteinase inhibitor and human leukocyte elastase is a neutrophil chemoattractant J Exp Med 167 1608–1615 Occurrence Handle3259253 Occurrence Handle1:CAS:528:DyaL1cXktlKnsLk%3D Occurrence Handle10.1084/jem.167.5.1608

    Article  PubMed  CAS  Google Scholar 

  15. EF Plow (1986) ArticleTitleThe contribution of leukocyte proteases to fibrinolysis Blut 53 1–9 Occurrence Handle3521765 Occurrence Handle1:CAS:528:DyaL28XlsFShtr0%3D Occurrence Handle10.1007/BF00320577

    Article  PubMed  CAS  Google Scholar 

  16. MS Brower DA Walz KE Garry JW Fenton Suffix2nd (1987) ArticleTitleHuman neutrophil elastase alters human α-thrombin function: limited proteolysis near the γ-cleavage site results in decreased fibrinogen clotting and platelet-stimulatory activity Blood 69 813–819 Occurrence Handle3101765 Occurrence Handle1:CAS:528:DyaL2sXhtlGqurg%3D

    PubMed  CAS  Google Scholar 

  17. M Taki T Miura M Inagaki Y Tomita N Saito Y Okada Y Tsuda T Meguro K Yamada (1986) ArticleTitleInfluence of granulocyte elastase-like proteinase (ELP) on platelet functions Thromb Res 41 837–846 Occurrence Handle3010492 Occurrence Handle1:CAS:528:DyaL28Xit1amt70%3D Occurrence Handle10.1016/0049-3848(86)90382-8

    Article  PubMed  CAS  Google Scholar 

  18. M Jochum S Lander N Heimburger H Fritz (1981) ArticleTitleEffect of human granulocytic elastase on isolated human antithrombin III Hoppe-Seyler's Z Physiol Chem 362 103–112 Occurrence Handle6783500 Occurrence Handle1:CAS:528:DyaL3MXhsFamsLg%3D

    PubMed  CAS  Google Scholar 

  19. P Bjørk L Axelsson M Bergenfeldt K Ohlsson (1988) ArticleTitleInfluence of plasma protease inhibitors and the secretory leukocyte protease inhibitor on leukocyte elastase-induced consumption of selected plasma proteins in vitro in man Scand J Clin Lab Invest 48 205–211 Occurrence Handle2451859

    PubMed  Google Scholar 

  20. P Henriksson IM Nilsson K Ohlsson P Stenberg (1980) ArticleTitleGranulocyte elastase activation and degradation of factor XIII Thromb Res 18 343–351 Occurrence Handle6903021 Occurrence Handle1:CAS:528:DyaL3cXlt12lsbw%3D Occurrence Handle10.1016/0049-3848(80)90329-1

    Article  PubMed  CAS  Google Scholar 

  21. T Nishiyama M Aibiki K Hanaoka (1996) ArticleTitleThe effect of ulinastatin, a human protease inhibitor, on the transfusion-induced increase of plasma polymorphonuclear granulocyte elastase Anesth Analg 82 108–112 Occurrence Handle8712383 Occurrence Handle1:CAS:528:DyaK28XhtFGktbc%3D Occurrence Handle10.1097/00000539-199601000-00019

    Article  PubMed  CAS  Google Scholar 

  22. S Gando T Kameue S Namzaki Y Nakanishi (1995) ArticleTitleCytokines, soluble thrombomodulin and disseminated intravascular coagulation in patients with systemic inflammatory response syndrome Thromb Res 80 519–526 Occurrence Handle8610280 Occurrence Handle1:CAS:528:DyaK28Xls1Sg Occurrence Handle10.1016/0049-3848(95)00207-3

    Article  PubMed  CAS  Google Scholar 

  23. D Massignon A Lepape J Bienvenu Y Barbier C Boileau P Coeur (1994) ArticleTitleCoagulation/fibrinolysis balance in septic shock related to cytokines and clinical state Haemostasis 24 36–48 Occurrence Handle7959354 Occurrence Handle1:STN:280:ByqD2cjosFE%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, The University of Tokyo, Tokyo, Japan

    Tomoki Nishiyama

  2. Department of Anesthesiology and Critical Care Medicine, Kochi University Medical School, Kochi, Japan

    Takeshi Yokoyama & Koichi Yamashita

Authors
  1. Tomoki Nishiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takeshi Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Koichi Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Nishiyama, T., Yokoyama, T. & Yamashita, K. Effects of a protease inhibitor, ulinastatin, on coagulation and fibrinolysis in abdominal surgery. J Anesth 20, 179–182 (2006). https://doi.org/10.1007/s00540-006-0396-7

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00540-006-0396-7

Key words

Search

Navigation