Plasma-derived human antithrombin attenuates ventilator-induced coagulopathy in a Streptococcus pneumoniae pneumonia model in rats
© BioMed Central Ltd 2009
Published: 11 November 2009
Pneumonia is characterized by local activation of coagulation leading to alveolar fibrin deposition. Lung injurious mechanical ventilation (LI-MV) with conventional tidal volumes (VT) and no positive end-expiratory pressure (PEEP) aggravates pulmonary coagulopathy. We hypothesized administration of anti-thrombin (AT), a natural anticoagulant, to attenuate ventilator-induced coagulopathy and inflammation in a rat model of Streptococcus pneumoniae pneumonia.
Rats challenged intratracheally with bacteria were ventilated 40 hours later (VT = 12 ml/kg/no PEEP) after systemicadministration of plasma-derived human AT (250 U/kg) or placebo for 3 hours. Endpoints: BALF levels of thrombin-antithrombin complexes (TATc), fibrin degradation products (FDP), AT, plasminogen activator activity (PAA), plasminogen activator inhibitor-1 (PAI-1), pulmonary cytokines and blood cultures. Data are presented as the mean ± SD. Statistics: one-way ANOVA with Dunn's multiple comparison test.
S. pneumoniae pneumonia was characterized by activation of coagulation (TATc, in pneumonia vs. healthy control, 3.7 ± 0.3 vs. 1.2 ± 0.5 ng/ml; FDP: 291 ± 40 vs. 15 ± 5 ng/ml; AT: 3.7 ± 0.3 vs. 20.0 ± 5.2 IU/ml - all P < 0.05) and inhibition of fibrinolysis (PAA: 99.2 ± 5.9 vs. 73.3 ± 5.7% of normal, P < 0.05, PAI-1: 1.9 ± 0.6 vs. 10.0 ± 1.4 ng/ml, P < 0.05). Systemic administration of AT resulted in supraphysiologic levels of BALF AT levels (25.4 ± 4.9 vs. 5.3 ± 1.0 IU/ml) and prevented further activation of coagulation by MV (TATc, in LI-MV with AT vs. placebo, 3.9 ± 0.3 vs. 6.5 ± 0.8 ng/ml - P < 0.05). No changes in pulmonary cytokines were observed between the infected and mechanically ventilated animals (TNF: LI-MV with AT vs. placebo, 1.6 ± 0.4 vs. 1.9 ± 1.3 ng/ml and IL-6: 2.5 ± 1.3 vs. 2.4 ± 1.4 ng/ml- P = NS). The infected animals showed similar numbers of bacteria in blood samples at the start of the experiment, which did not change during the experiment.
Systemic administration of AT attenuated ventilator-induced coagulopathy but not inflammation.