Alveolar fibrinolytic capacity suppressed by injurious mechanical ventilation

Objective: To investigate the effect of mechanical ventilation on alveolar fibrinolytic capacity. Design and setting: Randomized controlled animal study in 66 Sprague-Dawley rats. Subjects and interventions: Test animals received intratracheal fibrinogen and thrombin instillations; six were killed immediately (fibrin controls), and the others were allocated to three ventilation groups (ventilation period: 225 min) differing in positive inspiratory pressure and positive end-expiratory pressure, respectively: group 1, 16 cmH(2)O and 5 cmH(2)O (n=17); group 2, 26 cmH(2)O and 5 cmH(2)O (n=16); group 3, 35 cmH(2)O and of 5 cmH(2)O (n=17). Ten animals that had not been ventilated served as healthy controls. Measurements and results: After animals were killed, we measured D-dimers, plasminogen activator inhibitor (PAI) 1, and tumor necrosis factor α in the bronchoalveolar lavage fluid and calculated lung weight and pressure/volume (P/V) plots. The median D-dimer concentration (mg/l) decreased with increasing pressure amplitude (192 in group 1, IQR 119; 66 in group 2, IQR 107; 29 in group 3, IQR 30) while median PAI-1 (U/ml) increased (undetectable in group 1; 0.55 in group 2, IQR 4.55; 3.05 in group 3, IQR 4.85). PAI-1 level was correlated with increased lung weight per bodyweight (Spearman's rank correlation 0.708). Tumor necrosis factor α concentration was not correlated with PAI-1 level. Conclusions: Alveolar fibrinolytic capacity is suppressed during mechanical ventilation with high pressure amplitudes due to local production of PAI-1.