Alveolar fibrinolytic capacity suppressed by injurious mechanical ventilation.
OBJECTIVE
To investigate the effect of mechanical ventilation on alveolar fibrinolytic capacity.


METHODS
Randomized controlled animal study in 66 Sprague-Dawley rats.


METHODS
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.


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.
Dahlem
Peter
P
Pediatric Intensive Care Unit, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands. PDahlem@hotmail.com
Bos
Albert P
AP
Haitsma
Jack J
JJ
Schultz
Marcus J
MJ
Meijers
Joost C M
JC
Lachmann
Burkhard
B
D000704:Analysis of Variance; D000818:Animals; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis; D016014:Linear Models; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000503:physiopathology*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; C036309:fibrin fragment D