Effect of recombinant tissue plasminogen activator on intra-abdominal abscess formation in rats with generalized peritonitis.
BACKGROUND
During generalized peritonitis, intraabdominal fibrin deposition is stimulated whereas fibrinolytic activity is reduced, which predisposes intra-abdominal abscess formation. We investigated the effects of increasing the intra-abdominal fibrinolytic activity on abscess formation by intra-abdominal administration of recombinant tissue plasminogen activator (rt-PA). Potential side effects, such as bacteremia and bleeding, were also assessed.


METHODS
A rat model of generalized peritonitis, induced by intraperitoneal injection of sterile feces contaminated with 10(4) cfu per mL Escherichia coli (E. coli) and 10(4) cfu per mL Bacteroides fragilis, was used.


RESULTS
Rats treated with rt-PA dissolved in methyl hydroxy propyl cellulose (MHPC) gel (0.5 mg per mL), had significantly less intra-abdominal abscesses than rats in the control group, treated with either Ringer's lactate solution or MHPC gel alone (p < 0.01). Other than E. coli, cultures of abscesses revealed species originating from the intestine, demonstrating bacterial translocation. The mortality rate was significantly higher in the rats treated with rt-PA as compared with rats in the control group (p < 0.01), which was surprising considering the absence of bacteremia. By challenging the rats with a higher dose of E. coli, early bacteremia was observed in the rats treated with rt-PA, not related to increased mortality rates. Intraabdominal use of rt-PA was not associated with an increased incidence of bleeding events.


CONCLUSIONS
Recombinant tissue plasminogen activator prevents abscess formation in rats with generalized peritonitis. However, early bacteremia and increased mortality rates are serious drawbacks of the intra-abdominal use of rt-PA in this rat model.
van Goor
H
H
Department of Surgery, University Hospital, Groningen, The Netherlands.
de Graaf
J S
JS
Kooi
K
K
Sluiter
W J
WJ
Bom
V J
VJ
van der Meer
J
J
Bleichrodt
R P
RP
D018784:Abdominal Abscess / Q000382:microbiology / Q000517:prevention & control*; D000818:Animals; D001442:Bacteroides Infections / Q000517:prevention & control; D001441:Bacteroides fragilis; D004927:Escherichia coli Infections / Q000517:prevention & control; D008297:Male; D010538:Peritonitis / Q000150:complications* / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator