EFFECT OF RECOMBINANT TISSUE-PLASMINOGEN ACTIVATOR ON INTRAABDOMINAL ABSCESS FORMATION IN RATS WITH GENERALIZED PERITONITIS

BACKGROUND: During generalized peritonitis, intraabdominal fibrin depo sition is stimulated whereas fibrinolytic activity is reduced, which p redisposes intra-abdominal abscess formation. We investigated the effe cts of increasing the intra-abdominal fibrinolytic activity on abscess formation by intra-abdominal administration of recombinant tissue pla sminogen activator (rt-PA). Potential side effects, such as bacteremia and bleeding, were also assessed. STUDY DESIGN: A rat model of genera lized peritonitis, induced by intraperitoneal injection of sterile fec es 10(4) cfu per mt Escherichia cell contaminated with 10 (E. cell) an d 10(4) cfu per mt Bacteroides fragilis, was used. RESULTS: Rats treat ed with rt-PA dissolved in methyl hydroxy propyl cellulose (MHPC) gel (0.5 mg per mt), had significantly less intra-abdominal abscesses than rats in the control group, treated with either Ringer's lactate solut ion or MHPC gel alone (p<0.01). Other than E. cell, cultures of absces ses revealed species originating from the intestine, demonstrating bac terial translocation. The mortality rate was significantly higher in t he rats treated with rt-PA as compared with rats in the control group (p<0.01), which was suprising considering the absence of bacteremia. B y challenging the rats with a higher dose of E. cell, 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 ti ssue plasminogen activator prevents abscess formation in rats with gen eralized peritonitis. However, early bacteremia and increased mortalit y rates are serious drawbacks of the intra-abdominal use of rt-PA in t his rat model.