Tissue-type plasminogen activator prevents formation of intra-abdominal abscesses after surgical treatment of secondary peritonitis in a rat model

Int J Colorectal Dis. 2007 Jul;22(7):819-25. doi: 10.1007/s00384-006-0222-6. Epub 2006 Nov 7.

Abstract

Background: Optimal therapy of secondary peritonitis frequently results in the formation of residual abscesses, which bear a substantial mortality and morbidity. This study aims to prove that fibrinolytic therapy with recombinant tissue plasminogen activator (rtPA) can reduce abscess formation after surgical treatment of secondary peritonitis in a rat model, without causing unwanted side effects.

Materials and methods: Male Wistar rats received an intra-abdominal injection with a suspension of sterile feces, 10(5) cfu Escherichia coli and 10(4) cfu Bacteroides fragilis. Surgical debridement was performed 1 h after inoculation. Animals were randomized into four groups (n = 14 each). Three groups received human rtPA at 1 h (rtPA1); 1 h and 6 h (rtPA2); and 1, 6, and 24 h (rtPA3), respectively. Each dose contained 1.25 mg rtPA. Controls received saline only. Animals were killed after 5 days.

Results: rtPA treatment reduced abscess formation in surviving animals, depending on number of doses given. Animals in group rtPA3 had no abscesses in contrast to 88% of the controls (mean 3.6 +/- 2.7 abscesses per rat; p < 0.05). In the rtPA1 and rtPA2 group, frequency of abscess formation was 58 and 33%, respectively. Mortality, course of body weight, and bacteremia were not affected by rtPA and neither were peritoneal cell counts and levels of TNF-alpha, IL-1beta, IL-6 and IL-10. No bleeding complications were observed.

Conclusion: rtPA reduces intra-abdominal abscess formation after surgical treatment of generalized peritonitis without increasing mortality or affecting the local inflammatory response.

MeSH terms

  • Abdominal Abscess / etiology
  • Abdominal Abscess / metabolism
  • Abdominal Abscess / prevention & control*
  • Animals
  • Ascitic Fluid / cytology
  • Ascitic Fluid / metabolism
  • Cytokines / metabolism
  • Digestive System Surgical Procedures / adverse effects*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / therapeutic use*
  • Follow-Up Studies
  • Injections, Intraperitoneal
  • Leukocyte Count
  • Male
  • Peritonitis / metabolism
  • Peritonitis / surgery*
  • Rats
  • Rats, Wistar
  • Recombinant Proteins
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome

Substances

  • Cytokines
  • Fibrinolytic Agents
  • Recombinant Proteins
  • Tissue Plasminogen Activator