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

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 ftagilis. Surgical debridement was performed I h after inoculation. Animals were randomized into four groups (n=14 each). Three groups received human rtPA at I h (rtPAI); I 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-1 beta, 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.