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Alveolar fibrinolysis is not altered by mechanical ventilation in humans with healthy lungs
Critical Care volume 9, Article number: P95 (2005)
Mechanical ventilation (MV) aggravates pulmonary inflammation in patients with acute lung injury. Pulmonary inflammation is characterized by alveolar fibrin depositions, which is the net result of increased thrombin-mediated generation of fibrin and upregulation of plasminogen activator inhibitor (PAI), inhibiting fibrin degradation. We recently showed that injurious MV (using high pressures) induces PAI-1 upregulation in rats, thereby limiting pulmonary fibrinolytic activity. In the present study we determine the influence of MV on alveolar PAI-1 expression in humans with healthy lungs.
Patients with healthy lungs expected to be mechanically ventilated for ≥ 5 hours (elective surgery) were randomized to a MV strategy using either a tidal volume (VT) of 12 ml/kg and zero positive end expiratory pressure (HVT/ZEEP) or VT 6 ml/kg and 10 cmH2O PEEP (LVT/PEEP). Bronchoalveolar lavage (BAL) was performed directly after initiation of MV, and repeated in the contralateral lung after 5 hours of MV. Pulmonary thrombin generation was quantified by measuring thrombin–antithrombin complexes (TATc) in the BAL fluid; fibrinolytic activity by determining plasminogen activator activity (PAA), PAI-1, and tissue-type plasminogen activator (tPA).
Within groups, Wilcoxon signed-rank test; between groups, Mann–Whitney U test. Data are presented as medians with interquartile ranges.
Nine patients were randomized to HVT/ZEEP, 11 patients to LVT/PEEP. There were no differences in baseline characteristics or outcome. After 5 hours, patients ventilated with HVT/ZEEP showed an increase in alveolar thrombin generation (TATc: 0.91 [0.82–0.98] ng/ml vs 0.75 [0.67–0.81] ng/ml at baseline, P < 0.01), in contrast to those with LVT/PEEP (0.84 [0.74–0.91] ng/ml vs 0.81 [0.72–0.87] ng/ml, not significant [NS]). Pulmonary PAI-1 levels did not change (LVT/PEEP: 2.0 [1.6–2.2] ng/ml vs 1.9 [1.8–2.1] ng/ml, NS; HVT/ZEEP: 2.1 [1.8–2.1] ng/ml vs 2.0 [1.7–2.4] ng/ml, NS). Moreover, alveolar PAA was unaffected in both groups (LVT/PEEP: 106 [102–113]% vs 100 [97–105]%, NS; HVT/ZEEP: 102 [97–110]% vs 102 [100–104]%, NS), although levels of tPA increased more with HVT/ZEEP MV (LVT/PEEP: 0.84 [0.65–0.98] ng/ml vs 0.61 [0.55–0.63] ng/ml, P < 0.001; HVT/ZEEP: 0.70 [0.70–0.90] ng/ml vs 0.50 [0.40–0.55] ng/ml, P < 0.01; between groups, NS).
Despite upregulation of tPA, alveolar PAA is not altered during 5 hours of MV in patients with healthy lungs. Disturbed alveolar fibrin turnover during MV in healthy lungs seems solely the result of activation of coagulation.
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Choi, G., Wolthuis, E., Bresser, P. et al. Alveolar fibrinolysis is not altered by mechanical ventilation in humans with healthy lungs. Crit Care 9, P95 (2005). https://doi.org/10.1186/cc3158
- Mechanical Ventilation
- Acute Lung Injury
- Thrombin Generation