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 pathway inhibitor (TFPI), an inhibitor of the extrinsic coagulation pathway, can improve survival in a clinically relevant model of gram-negative sepsis, rabbits were given an intraperitoneal inoculation of a suspension containing hemoglobin (40 microg/mL), porcine mucin (150 microg/mL), and viable Escherichia coli O18:K1 (1.0 +/- 0.5 x 10(5) cfu/kg). Treatment with gentamicin (5 mg/kg every 12 h for five doses) was instituted 4 h after induction of peritonitis. At the same time point, rabbits were randomized to receive a 24-h infusion of vehicle or one of three different doses of TFPI. Treatment groups, 7-day survival rates, and significance versus control were as follows: control, 1 of 20; TFPI(LOW DOSE) (0.1 mg/kg, then 1 microg/kg/min), 3 of 12 (P = .14); TFPI(MID DOSE), (0.5 mg/kg, then 5 microg/kg/min), 7 of 12 (P = .002); TFPI(HIGH DOSE) (10 mg/kg, then 10 microg/kg/min), 4 of 13 (P = .04). Thus, delayed treatment with TFPI improves survival in septic rabbits.
Camerota
A J
AJ
Department of Anesthesia, Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Creasey
A A
AA
Patla
V
V
Larkin
V A
VA
Fink
M P
MP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000401:mortality; D005839:Gentamicins / Q000627:therapeutic use; D006801:Humans; D008074:Lipoproteins / Q000008:administration & dosage*; D010100:Oxygen / Q000097:blood; D010538:Peritonitis / Q000188:drug therapy* / Q000401:mortality; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality; D013925:Thromboplastin
D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D005839:Gentamicins; D008074:Lipoproteins; D011994:Recombinant Proteins; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D010100:Oxygen