Alveolar fibrinolytic capacity suppressed by injurious mechanical ventilation

Intensive Care Med. 2005 May;31(5):724-32. doi: 10.1007/s00134-005-2588-2. Epub 2005 Mar 8.


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 cmH2O and 5 cmH2O (n=17); group 2, 26 cmH2O and 5 cmH2O (n=16); group 3, 35 cmH2O and of 5 cmH2O (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 alpha 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 alpha 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.

Publication types

  • Evaluation Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinolysis*
  • Linear Models
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Positive-Pressure Respiration / adverse effects*
  • Pulmonary Alveoli / metabolism*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / physiopathology*
  • Survival Analysis
  • Tumor Necrosis Factor-alpha / metabolism


  • Fibrin Fibrinogen Degradation Products
  • Plasminogen Activator Inhibitor 1
  • Tumor Necrosis Factor-alpha
  • fibrin fragment D