TY - JOUR T1 - Mechanical ventilation affects alveolar fibrinolysis in LPS-induced lung injury JF - European Respiratory Journal JO - Eur Respir J SP - 992 LP - 998 DO - 10.1183/09031936.06.00133104 VL - 28 IS - 5 AU - P. Dahlem AU - A. P. Bos AU - J. J. Haitsma AU - M. J. Schultz AU - E. K. Wolthuis AU - J. C. M. Meijers AU - B. Lachmann Y1 - 2006/11/01 UR - http://erj.ersjournals.com/content/28/5/992.abstract N2 - 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. ER -