Thromb Haemost 2004; 91(03): 497-505
DOI: 10.1160/TH03-08-0529
Theme Issue Article
Schattauer GmbH

Enhancement of endogenous fibrinolysis does not reduce local fibrin deposition, but modulates inflammation upon intestinal ischemia and reperfusion

Authors

  • Ivo G. Schoots

    1   Departments of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands
    2   Vascular and Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands
  • Marcel Levi

    2   Vascular and Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands
  • Arlène K. van Vliet

    1   Departments of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands
  • Paul J. Declerck

    3   Laboratory for Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, University of Leuven, Belgium
  • Adrie M. Maas

    1   Departments of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands
  • Thomas M. van Gulik

    1   Departments of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands
Weitere Informationen

Publikationsverlauf

Received 20. August 2003

Accepted after revision 07. Januar 2003

Publikationsdatum:
05. Dezember 2017 (online)

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Summary

This study investigated the contribution of endogenous suppression of fibrinolysis and increased fibrin deposition to intestinal dysfunction and injury in a rat model of intestinal ischemia/ reperfusion (I/R), as fibrinolytic inhibition may lead to thrombotic obstructions that compromise microcirculation and promote intestinal injury. Circulatory fibrinolysis was enhanced by intravenous administration of recombinant tissue plasminogen activator (rt-PA) or by inhibition of PAI-1 by administration of MA-33H1F7. Coagulation and fibrinolysis parameters obtained from portal blood were correlated to fibrin deposition (determined by anti-rat fibrin antibody staining), intestinal function (glucose/water clearance) and intestinal injury (histological evaluation by Park/Chiu score).

Enhanced circulatory fibrinolytic activity, as evidenced by increased portal plasma plasminogen activator activity, elevated fibrin degradation products and decreased levels of PAI-1, did not reduce mucosal fibrin deposition and microthrombosis in postischemic intestinal tissue. Furthermore, rt-PA or anti-PAI-1 antibody administration did not attenuate I/R-induced intestinal injury or dysfunction, as demonstrated by intestinal histopathology scores of 4.8±0.2 and 4.7±0.3 (control I/R group 4.7±0.2) and glucose clearances of 47±6 and 46±9 µL/min · g (control I/R group 30±8 µL/min · g) after 40 minutes of intestinal ischemia and 3 hours of reperfusion, respectively. However, both interventions resulted in decreased levels of interleukin-6, which may indicate fibrin-induced modulation of inflammation. Attempts to enhance the fibrinolytic activity (either by rt-PA or by anti-PAI-1 administration), indicated by increased portal plasma levels of released FDP, failed to decrease mucosal fibrin deposition and to attenuate intestinal I/R injury. Based on our observations and previous reports, the contribution of suppressed endogenous fibrinolysis to microcirculatory fibrin deposition and I/R-injury may be of limited importance.