Summary
This study was designed to determine the effect of a delayed infusion (T+120 min)
of alanyl tissue factor pathway inhibitor (ala-TFPI) on the response to LD100 E. coli. We hypothesized that baboons treated with a low dose of TFPI (5 mg/kg) which did
not survive would exhibit thrombosis, infarction and hemorrhage of target tissues
such as that seen in untreated animals infused with LD100 E. coli. Eight baboons were infused with 5 mg/kg of ala-TFPI over a 10 h period beginning
immediately after a 2 h infusion of LD100 E. coli (experimental group). Four baboons 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 thrombosis, necrosis, hemorrhage, and congestion of target tissues and for changes
in clinical chemical parameters. We expected that failure to protect would correlate
with failure to inhibit thrombosis of target tissue (8). Surprisingly ala-TFPI significantly
inhibited thrombosis, hemorrhage and necrosis of adrenal and renal tissues and attenuated
the rise 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 begun as late as T+120 in minutes failed to
protect against the lethal effects of LD100 E. coli in spite of completely preventing thrombosis and hemorrhage in target organs, and
that thrombosis, infarction and hemorrhage of adrenal and renal tissue are not part
of the lethal chain of events in this IV model of E. coli sepsis.
