ATTENUATION OF TISSUE THROMBOSIS AND HEMORRHAGE BY ALA-TFPI DOES NOT ACCOUNT FOR ITS PROTECTION AGAINST ESCHERICHIA-COLI - A COMPARATIVE-STUDY OF TREATED AND UNTREATED NON-SURVIVING BABOONS CHALLENGED WITH LD100 ESCHERICHIA-COLI

This study was designed to determine the effect of a delayed infusion (T+120 min) of alanyl tissue factor pathway inhibitor (ala-TFPI) on th e response to LD100 E. coil. We hypothesized that baboons treated with a low dose of TFPI (5 mg/kg) which did not survive would exhibit thro mbosis, infarction and hemorrhage of target tissues such as that seen in untreated animals infused with LD100 E. coli. Eight baboons were in fused with 5 mg/kg of ala-TFPI over a 10 h period beginning immediatel y after a 2 h infusion of LD100 E. coil (experimental group). Four bab oons were infused with E. coli followed by a 10 h infusion of saline ( control group). Of the 12 baboons, the 11 non-survivors (TFPI = 7 out of 8; controls = 4 out of 4) were evaluated for the extent of thrombos is. necrosis, hemorrhage, and congestion of target tissues and for cha nges in clinical chemical parameters. We expected that failure to prot ect would correlate with failure to inhibit thrombosis of target tissu e (8). Surprisingly ala-TFPI significantly inhibited thrombosis, hemor rhage and necrosis of adrenal and renal tissues and attenuated the ris e in creatinine in the 7 treated non-survivors. The lungs of these non -survivors, however, exhibited intra-alveolar fibrin and a mild degree of hemorrhage and edema. We concluded that low doses of ala-TFPI begu n as late as T+120 in minutes failed to protect against the lethal eff ects of LD100 E. coli in spite of completely preventing thrombosis and hemorrhage in target organs, and that thrombosis, infarction and hemo rrhage of adrenal and renal tissue are not part of the lethal chain of events in this IV model of E. coli sepsis.