Alveolar fibrinolytic capacity suppressed by injurious mechanical ventilation

• Published in: Intensive care medicine Vol. 31; no. 5; pp. 724 - 732
• Main Authors: DAHLEM, Peter, BOS, Albert P, HAITSMA, Jack J, SCHULTZ, Marcus J, MEIJERS, Joost C. M, LACHMANN, Burkhard
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-05-2005; Berlin Springer Nature B.V
• Subjects: Acute respiratory distress syndrome; Analysis of Variance; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Artificial respiration; Biological and medical sciences; Care and treatment; Case studies; Emergency and intensive care: renal failure. Dialysis management; Emergency and intensive respiratory care; Fibrin Fibrinogen Degradation Products - metabolism; Fibrinolysis; Intensive care medicine; Linear Models; Medical sciences; Plasminogen Activator Inhibitor 1 - metabolism; Positive-Pressure Respiration - adverse effects; Pulmonary Alveoli - metabolism; Random Allocation; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome, Adult - etiology; Respiratory Distress Syndrome, Adult - physiopathology; Survival Analysis; Tumor Necrosis Factor-alpha - metabolism; Netherlands; Animal experimentation; Intensive care; Adult respiratory distress syndrome; Animal; Adult respiratory distress syndrome ·Artificial ventilation; Experimentation; Artificial ventilation; Fibrinolysis; Trauma; Mechanical ventilation; Fibrinolytic; Resuscitation
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-005-2588-2

To investigate the effect of mechanical ventilation on alveolar fibrinolytic capacity.
Randomized controlled animal study in 66 Sprague-Dawley rats.
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.
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.
Alveolar fibrinolytic capacity is suppressed during mechanical ventilation with high pressure amplitudes due to local production of PAI-1.