Preventing
tissue-factor-(TF-) mediated systemic coagulopathy improves outcome in models of
sepsis. Preventing TF-mediated pulmonary coagulopathy could attenuate
ventilator-induced lung injury (VILI). We investigated the effect of relative TF deficiency on pulmonary coagulopathy and
inflammation in a murine model of VILI. Heterozygous TF knockout (TF(+/-)) mice and their wild-type (TF(+/+)) littermates were sedated (controls) or sedated, tracheotomized, and mechanically ventilated with either low or high tidal volumes for 5 hours.
Mechanical ventilation resulted in pulmonary coagulopathy and
inflammation, with more injury after
mechanical ventilation with higher tidal volumes. Compared with TF(+/+) mice, TF(+/-) mice demonstrated significantly lower pulmonary
thrombin-antithrombin complex levels in both ventilation groups. There were, however, no differences in
lung wet-to-dry ratio, BALF total
protein levels, neutrophil influx, and lung histopathology scores between TF(+/-) and TF(+/+) mice. Notably, pulmonary levels of
cytokines were significantly higher in TF(+/-) as compared to TF(+/+) mice. Systemic levels of
cytokines were not altered by the relative absence of TF. TF deficiency is associated with decreased pulmonary coagulation independent of the ventilation strategy. However, relative TF deficiency does not reduce VILI and actually results in higher pulmonary levels of inflammatory mediators.