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.


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.


CONCLUSIONS
rtPA reduces intra-abdominal abscess formation after surgical treatment of generalized peritonitis without increasing mortality or affecting the local inflammatory response.
Buyne
Otmar R
OR
Department of Surgery, Radboud University Nijmegen Medical Centre, P.O. Box 91091, 6500, HB Nijmegen, The Netherlands.
Bleichrodt
Robert P
RP
van Goor
Harry
H
Verweij
Paul E
PE
Hendriks
Thijs
T
D018784:Abdominal Abscess / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D013505:Digestive System Surgical Procedures / Q000009:adverse effects*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005500:Follow-Up Studies; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D008297:Male; D010538:Peritonitis / Q000378:metabolism / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D016207:Cytokines; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator