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Thromb Haemost 2000; 84(05): 876-881
DOI: 10.1055/s-0037-1614131
Review Article
Schattauer GmbH

Short-term Effect of Surgical Trauma on Rat Peritoneal Fibrinolytic Activity and Its Role in Adhesion Formation

B. W. J. Hellebrekers
1   From the Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands
,
G. C. M. Trimbos-Kemper
1   From the Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands
,
E. A. Bakkum
1   From the Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands
,
J. B. M. Z. Trimbos
1   From the Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands
,
P. J. Declerck
2   Laboratory for Pharmaceutical Biology and Phytopharmacology, University of Leuven, Leuven, Belgium
,
T. Kooistra
3   Gaubius Laboratory, TNO Prevention and Health, Leiden, the Netherlands
,
J. J. Emeis
3   Gaubius Laboratory, TNO Prevention and Health, Leiden, the Netherlands
› Institutsangaben
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Publikationsverlauf

Received 28. Dezember 1999

Accepted after revision 14. Juni 2000

Publikationsdatum:
13. Dezember 2017 (online)

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Summary

Background

Fibrin deposition, the primary step in the formation of post-surgical adhesions, is the result of a disbalance between the fibrinforming and the fibrin-dissolving capacity of the peritoneum. Literature data suggest a transient reduction in local plasminogen activator activity after peritoneal trauma, which results in a reduction of fibrinolysis and permits deposited fibrin to become organized into fibrous, permanent adhesions. In the present study, the fibrinolytic parameters tissue-type plasminogen activator (tPA; antigen and activity) and plasminogen activator inhibitor type-1 (PAI-1; antigen and activity) were measured in peritoneal fluid, in peritoneal biopsies and in plasma to establish the time course of changes in fibrinolytic activity.

Design

A standardized peritoneal adhesion model in the rat.

Outcome Measures

Analysis, over a 72-h period following surgical trauma, of the main fibrinolytic parameters in peritoneal lavage, in biopsies of damaged and undamaged peritoneum, and in plasma, and determination of fibrin and fibrin(ogen)-degradation products in peritoneal lavage fluid.

Results

At all time intervals, tPA antigen was found to be about six-fold increased in peritoneal lavage after surgical trauma. This significant rise in tPA antigen was accompanied by a large increase in its main inhibitor PAI-1, resulting in tPA activity levels similar to, or slightly higher than, those found in control animals. tPA activity was lowest at 4 h and increased thereafter. Also in biopsies from damaged peritoneum, tPA antigen was significantly increased. Tissue tPA activity was also lowest at 4 h, after which it increased, significantly so at 24 and 72 h. Similar, though smaller, changes were seen in the biopsies from undamaged areas of the peritoneal wall in operated rats. PAI-1 (antigen and activity) was not detected in peritoneal biopsies. Fibrin-related material (especially fibrin monomer/fibrinogen, an indicator of forming fibrin) in peritoneal fluid was slightly increased at 4 h, and abundantly present at 16 and 24 h, returning to control levels at 72 h. Fibrin degradation products were always present. From 2 h onward, adhesions were found.

Conclusions

In contrast to the view that adhesions are formed as a result of a reduced fibrinolytic activity, our results demonstrate that tPA activity remained unchanged or slightly increased after surgical trauma, and point to increased fibrin formation rather than diminished fibrinolytic activity as the main cause of fibrin deposition after peritoneal trauma. Therapies directed at prevention of adhesion formation should therefore aim at avoiding massive fibrin production and at promoting fibrinolytic activity during the early period after trauma.

Key words

Rat - peritoneum - adhesions - fibrin - fibrinolysis - tissue-type plasminogen activator - plasminogen activator inhibitor type-1
 

  • References

  • 1 Ellis H, Moran BJ, Thompson JN, Parker MC. et al. Adhesion-related hospital readmisions after abdominal and pelvic surgery: a retrospective cohort study. Lancet 1999; 353: 1476-80.
    CrossrefPubMedGoogle Scholar
  • 2 Peters AA, Trimbos-Kemper GC, Admiraal C, Trimbos JB, Hermans J. A randomized clinical trial on the benefit of adhesiolysis in patients with intraperitoneal adhesions and pelvic pain. Br J Obst Gyn 1992; 99: 59-62.
    CrossrefPubMedGoogle Scholar
  • 3 Trimbos-Kemper TC, Trimbos JB, van Hall EV. Adhesion formation in tubal surgery: results of the eight day laparoscopy in 188 patients. Fertil Steril 1985; 43: 395-400.
    CrossrefPubMedGoogle Scholar
  • 4 Bronson RA, Wallace EE. Lysis of periadnexal adhesions for correction of infertility. Fertil Steril 1977; 28: 613-9.
    CrossrefPubMedGoogle Scholar
  • 5 diZerega GS. Biochemical events in peritoneal tissue repair. Eur J Surg 1997; (Suppl. 577) 10-6.
    PubMedGoogle Scholar
  • 6 Holmdahl L. The role of fibrinolysis in adhesion formation. Eur J Surg 1997; Suppl 577: 24-31.
    PubMedGoogle Scholar
  • 7 Vipond MN, Whawell SA, Thompson JN, Dudley HAF. Peritoneal fibrinolytic activity and intra-abdominal adhesions. Lancet 1990; 335: 1120-2.
    CrossrefPubMedGoogle Scholar
  • 8 Hartwell SW. The mechanics of healing in human wounds. Springfield (IL): Thomas; 1955
    Google Scholar
  • 9 Myhre-Jensen O, Larsen SB, Astrup T. Fibrinolytic activity in serosal and synovial membranes. Arch Path 1969; 88: 623-30.
    PubMedGoogle Scholar
  • 10 Gervin AS, Puckett CL, Silver D. Serosal hypofibrinolysis, a cause of postoperative adhesions. Am J Surg 1973; 125: 80-8.
    CrossrefPubMedGoogle Scholar
  • 11 Buckman RF, Woods M, Sargent L, Gervin AS. A unifying pathogenetic mechanism in the etiology of intraperitoneal adhesions. J Surg Res 1976; 20: 1-5.
    CrossrefPubMedGoogle Scholar
  • 12 Buckman RF, Buckman PD, Hufnagel HV, Gervin AS. A physiologic basis for the adhesion-free healing of deperitonealized surfaces. J Surg Res 1976; 21: 67-76.
    CrossrefPubMedGoogle Scholar
  • 13 Raftery AT. Effect of peritoneal trauma on peritoneal fibrinolytic activity and intraperitoneal adhesion formation. Eur Surg Res 1981; 13: 397-401.
    CrossrefPubMedGoogle Scholar
  • 14 Thompson JN, Paterson-Brown S, Harbourne T, Whawell SA, Kalodiki E. DudleyHAF Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation. Br J Surg 1989; 76: 382-4.
    CrossrefPubMedGoogle Scholar
  • 15 Dörr PJ, Brommer EJP, Dooijewaard G, Vemer HM. Peritoneal fluid and plasma fibrinolytic activity in women with pelvic inflammatory disease. Thromb Haemost 1992; 68: 102-5.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 16 Whawell SA, Vipond MN, Scott-Coombes DM, Thompson JN. Plasminogen activator inhibitor 2 reduces peritoneal fibrinolytic activity in inflammation. Br J Surg 1993; 80: 107-9.
    CrossrefPubMedGoogle Scholar
  • 17 Scott-Coombes DM, Whawell SA, Vipond MN, Thompson JN. Elective surgery inhibits intraperitoneal fibrinolysis (abstract). Br J Surg 1994; 81: 770.
    PubMedGoogle Scholar
  • 18 Scott-Coombes DM, Whawell SA, Vipond MN, Thompson JN. Human intraperitoneal fibrinolytic response to elective surgery. Br J Surg 1995; 82: 414-7.
    CrossrefPubMedGoogle Scholar
  • 19 Ryan GB, Grobéty J, Majno G. Mesothelial injury and recovery. Am J Path 1973; 71: 93-112.
    PubMedGoogle Scholar
  • 20 Raftery AT. Regeneration of peritoneum: a fibrinolytic study. J Anat 1979; 129: 659-64.
    PubMedGoogle Scholar
  • 21 Vipond MN, Whawell SA, Thompson JN, Dudley AF. Effect of experimental peritonitis and ischaemia on peritoneal fibrinolytic activity. Eur J Surg 1994; 160: 471-7.
    PubMedGoogle Scholar
  • 22 Bouckaert PXJM, Land JA, Brommer EJP, Emeis JJ, Evers JLH. The impact of peritoneal trauma on intra-abdominal fibrinolytic activity, adhesion formation and early embryonic development in a rabbit longitudinal model. Hum Rep 1990; 05: 237-41.
    CrossrefPubMedGoogle Scholar
  • 23 Bakkum EA, Emeis JJ, Dalmeijer RAJ, van Blitterswijk CA, Trimbos JB, Trimbos-Kemper TCM. Long-term analysis of peritoneal plasminogen activator activity and adhesion formation after surgical trauma in the rat model. Fertil Steril 1996; 66: 1018-22.
    CrossrefPubMedGoogle Scholar
  • 24 Bakkum EA, Van Blitterswijk CA, Dalmeijer RAJ, Trimbos JB. A semiquantitative rat model for intraperitoneal postoperative adhesion formation. Gynecol Obstet Invest 1994; 37: 99-105.
    CrossrefPubMedGoogle Scholar
  • 25 Padró T, van den Hoogen CM, Emeis JJ. Distribution of tissue-type plasminogen activator (activity and antigen) in rat tissues. Blood Coagul Fibrinol 1990; 01: 601-8.
    PubMedGoogle Scholar
  • 26 Padró T, van den Hoogen CM, Emeis JJ. Plasmin inhibitory effect of rat tissues: comparison with antiplasmin activity of plasma. Scand J Clin Lab Invest 1991; 51: 599-603.
    CrossrefPubMedGoogle Scholar
  • 27 Emeis JJ, Hoekzema R, de Vos AF. Inhibiting interleukin-1 and tumor necrosis factor-a does not reduce induction of plasminogen activator inhibitor type-1 by endotoxin in rats in vivo. Blood 1995; 85: 115-20.
    PubMedGoogle Scholar
  • 28 Ngo TH, Verheyen S, Knockaert I, Declerck PJ. Monoclonal antibodybased immunoassays for the specific quantitation of rat PAI-1 antigen and activity in biological samples. Thromb Haemost 1998; 79: 808-12.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 29 Verheijen JH, Mullaart E, Chang GTG, Kluft C, Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue type) plasminogen activator applicable to measurements in plasma. Thromb Haemost 1992; 48: 266-9.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 30 Koopman J, Maas A, Rezaee F, Havekes L, Verheijen J, Gijbels M, Haverkate F. Fibrinogen and atherosclerosis: a study in transgenic mice. Fibrinol Proteol 1997; 11 (Suppl. 01) 19-21.
    PubMedGoogle Scholar
  • 31 Lansink M, Jong M, Bijsterbosch BekkersM, Toet K, Havekes LM, Emeis JJ, Kooistra T. Increased clearance explains lower plasma levels of tissuetype plasminogen activator by estradiol Evidence for potently enhanced mannose receptor expression in mice. Blood 1999; 94: 1330-6.
    PubMedGoogle Scholar
  • 32 Holmdahl L, Eriksson E, Al-Jabreen M, Risberg B. Fibrinolysis in human peritoneum during operation. Surgery 1996; 119: 701-5.
    CrossrefPubMedGoogle Scholar
  • 33 Holmdahl L, Falkenberg M, Ivarsson ML, Risberg B. Plasminogen activators and inhibitors in peritoneal tissue. APMIS 1997; 105: 25-30.
    CrossrefPubMedGoogle Scholar
  • 34 Padro T, Quax PHA, van den Hoogen CM, Roholl P, Verheijen J, Emeis JJ. Tissue-type plasminogen activator and its inhibitor in rat aorta Effect of endotoxin. Arterioscler Thromb 1994; 14: 1459-65.
    CrossrefPubMedGoogle Scholar
  • 35 Emeis JJ, van den Eijnden-Schrauwen Y, van den Hoogen CM, de Priester W, Lupu F. An endothelial storage granule for tissue-type plasminogen activator. J Cell Biol 1997; 139: 245-56.
    CrossrefPubMedGoogle Scholar
  • 36 Holmdahl L, Eriksson E, Eriksson BI, Risberg B. Depression of peritoneal fibrinolysis during operation is a local response to trauma. Surgery 1998; 123: 539-44.
    CrossrefPubMedGoogle Scholar
  • 37 Ivarsson ML, Bergstrom M, Eriksson E, Risberg B, Holmdahl L. Tissue markers as predictors of postoperative adhesions. Br J Surg 1998; 85: 1549-54.
    CrossrefPubMedGoogle Scholar
  • 38 Bakkum EA, Trimbos-Kemper TCM. Natural course of postsurgical adhesions. Microsurg 1995; 16: 650-4.
    CrossrefPubMedGoogle Scholar
  • 39 Harris ES, Morgan RF, Rodeheaver GT. Analysis of the kinetics of peritoneal adhesion formation in the rat and evaluation of potential antiadhesive agents. Surgery 1995; 117: 663-9.
    CrossrefPubMedGoogle Scholar