DELAYED TREATMENT WITH RECOMBINANT HUMAN TISSUE FACTOR PATHWAY INHIBITOR IMPROVES SURVIVAL IN RABBITS WITH GRAM-NEGATIVE PERITONITIS

To determine whether treatment with recombinant human tissue factor pa thway inhibitor (TFPI), an inhibitor of the extrinsic coagulation path way, can improve survival in a clinically relevant model of gram-negat ive sepsis, rabbits were given an intraperitoneal inoculation of a sus pension containing hemoglobin (40 mu g/mL), porcine mucin (150 mu g/mL ), and viable Escherichia coli O18:K1 (1.0 +/- 0.5 x 10(5) cfu/kg). Tr eatment with gentamicin (5 mg/kg every 12 h for five doses) was instit uted 4 h after induction of peritonitis. At the same time point, rabbi ts were randomized to receive a 24-h infusion of vehicle or one of thr ee different doses of TFPI, Treatment groups, 7-day survival rates, an d significance versus control were as follows: control, 1 of 20; TFPIL OW DOSE (0.1 mg/kg, then 1 mu g/kg/min), 3 of 12 (P = .14); TFPIMID DO SE, (0.5 mg/kg, then 5 mu g/kg/min), 7 of 12 (P = .002); TFPIHIGH DOSE (10 mg/kg, then 10 mu g/kg/min), 4 of 13 (P = .04), Thus, delayed tre atment with TFPI improves survival in septic rabbits.