The aim of the present study was to determine the effects of mechanical ventilation on alveolar fibrin turnover in lipopolysaccharide (LPS)-induced lung injury. In a randomised controlled trial, Sprague-Dawley rats (n=61) were allocated to three ventilation groups after intratracheal LPS (Salmonella enteritidis) instillations. Group I animals were subjected to 16 cmH2O positive inspiratory pressure (PIP) and 5 CMH2O positive end-expiratory pressure (PEEP); group II animals to 26 cmH2O PIP and 5 cmH2O PEEP; and group III animals to 35 cmH2O PIP and 5 CMH2O PEEP. Control rats (not mechanically ventilated) received LPS. Healthy rats served as a reference group. Levels of thrombin-antithrombin complex (TATc), D-dimer, plasminogen activator inhibitor (PAI) activity and PAI-1 antigen in bronchoalveolar lavage fluid were measured. LPS-induced lung injury increased TATc, D-dimer and PAI activity and PAI-1 antigen levels versus healthy animals. High pressure-amplitude ventilation increased TATc concentrations. D-dimer concentrations were not significantly raised. Instead, PAI activity increased with the amplitude of the pressure, from 0.7 U·mL-1 in group I to 3.4 U.mL-1 in group II and 5.0 U·mL-1 in group III. There was no change in PAI-1 antigen levels. In conclusion, mechanical ventilation creates an alveolar/pulmonary anti-fibrinolytic milieu in endotoxin-induced lung injury which, at least in part, might be due to an increase in plasminogen activator inhibitor activity. Copyright

Adult respiratory distress syndrome, Animal experimentation, Endotoxin, Fibrinolysis, Mechanical ventilation
dx.doi.org/10.1183/09031936.06.00133104, hdl.handle.net/1765/64725
The European Respiratory Journal
Department of Anesthesiology

Dahlem, P, Bos, A.P, Haitsma, J.J, Schultz, M.J, Wolthuis, E.K, Meijers, J.C.M, & Lachmann, B.F. (2006). Mechanical ventilation affects alveolar fibrinolysis in LPS-induced lung injury. The European Respiratory Journal, 28(5), 992–998. doi:10.1183/09031936.06.00133104