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Compartmentalized anti-inflammatory effects after topical activation of fibinolysis by tissue plasminogen activator in experimental polymicrobial peritonitis

Introduction

During secondary peritonitis, intra-abdominally formed fibrin entraps bacteria that are thereby difficult to eliminate by host defence mechanisms. Activating fibrinolysis may have beneficial effects on bacterial clearance and thus on inflammatory responses. Systemic fibrinolysis has risks of major bleeding complications. In this study, tissue-type plasminogen activator (tPA) was administered topically 24 hours after induction of peritonitis to examine the effects of fibrinolysis on local (abdominal) and distant (circulatory and pulmonary) inflammatory responses during polymicrobial peritonitis.

Methods

C57BL/6 mice underwent cecal ligation and puncture (CLP) or sham operation with, after 24 hours, relaparotomy and therapeutic peritoneal lavage with either saline or tPA (0.5 mg/ml). Inflammatory response, coagulation and fibrinolysis were assessed in peritoneal fluid, systemic circulation and lung compartments.

Results

CLP increased bacterial load, neutrophil influx and activity, coagulation and fibrinolysis compared with sham (all parameters P < 0.01). Compared with saline lavage, tPA lavage reduced intra-abdominal bacterial load, KC concentration and thrombin–anti-thrombin complexes (all P < 0.05), and also reduced intra-abdominal as well as pulmonary neutrophil influx and activity, and clotting times (all P < 0.05). Mediator levels of fibrinolysis were not significantly altered by tPA; histology showed less fibrin deposititions concomitant with reduced peritoneal, liver and lung damage after tPA lavage (P < 0.05). Mortality decreased from 50% to 35% (P = 0.3). Different kinetics were seen when comparing abdominal and pulmonary compartments.

Conclusions

In this model of polymicrobial peritonitis, abdominal activation of fibrinolysis by tPA lavage effectively reduced intra-abdominal bacterial load, thereby reducing inflammatory responses in abdominal and extra-abdominal compartments and remote fibrin deposits and tissue damage. Different kinetics between peritoneal, systemic and pulmonary compartments suggested compartmentalised responses.

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van Veen, S., van Vliet, A., van Gulik, T. et al. Compartmentalized anti-inflammatory effects after topical activation of fibinolysis by tissue plasminogen activator in experimental polymicrobial peritonitis. Crit Care 9, P154 (2005). https://doi.org/10.1186/cc3217

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Keywords

  • Peritonitis
  • Plasminogen Activator
  • Peritoneal Lavage
  • Cecal Ligation
  • Secondary Peritonitis