Mechanical ventilation affects alveolar fibrinolysis in LPS-induced lung injury

Abstract

The aim of the present study was to determine the effects of mechanical ventilation on alveolar fibrin turnover in lipopolysaccharide (LPS)-induced lung injury.In a randomised controlled trial, Sprague-Dawley rats (n561) were allocated to three ventilation groups after intratracheal LPS (Salmonella enteritidis) instillations. Group I animals were subjected to 16 cmH 2 O positive inspiratory pressure (PIP) and 5 cmH 2 O positive end-expiratory pressure (PEEP); group II animals to 26 cmH 2 O PIP and 5 cmH 2 O PEEP; and group III animals to 35 cmH 2 O PIP and 5 cmH 2 O PEEP. Control rats (not mechanically ventilated) received LPS. Healthy rats served as a reference group. Levels of thrombin-antithrombin complex (TATc), D-dimer, plasminogen activator inhibitor (PAI) activity and PAI-1 antigen in bronchoalveolar lavage fluid were measured.LPS-induced lung injury increased TATc, D-dimer and PAI activity and PAI-1 antigen levels versus healthy animals. High pressure-amplitude ventilation increased TATc concentrations.D-dimer concentrations were not significantly raised. Instead, PAI activity increased with the amplitude of the pressure, from 0.7 U?mL -1 in group I to 3.4 U?mL -1 in group II and 5.0 U?mL -1 in group III. There was no change in PAI-1 antigen levels.In conclusion, mechanical ventilation creates an alveolar/pulmonary anti-fibrinolytic milieu in endotoxin-induced lung injury which, at least in part, might be due to an increase in plasminogen activator inhibitor activity.

Ventilator-induced coagulopathy in experimentalStreptococcus pneumoniaepneumonia

“…It was recently shown in a rat model of MV that the use of increasing VT, but similar PEEP levels, caused a shift in alveolar fibrin turnover, mainly due to higher levels of PAI-1 in the lungs of these animals [12,13]. In addition, a recent study reported on patients without pre-existing lung injury who were intubated and mechanically ventilated because of elective surgery [27].…”

“…MV alone has been demonstrated to affect pulmonary coagulation in other preclinical animal models, as well as in one clinical study [12,13,27]. It was recently shown in a rat model of MV that the use of increasing VT, but similar PEEP levels, caused a shift in alveolar fibrin turnover, mainly due to higher levels of PAI-1 in the lungs of these animals [12,13].…”

“…Recently, it was demonstrated that in models of VILI, local pulmonary fibrinolysis is suppressed during injurious mechanical ventilation known as ventilator-associated coagulopathy [12,13]. However, the models used were iatrogenic in nature, either a single exposure to lipopolysaccharide [13] or fibrin deposits caused by human plasma without inflammation [12].…”

“…However, the models used were iatrogenic in nature, either a single exposure to lipopolysaccharide [13] or fibrin deposits caused by human plasma without inflammation [12]. Furthermore, in neither of these models was systemic analysis performed.…”

Neither fibrin nor plasminogen activator inhibitor-1 deficiency protects lung function in a mouse model of acute lung injury

“…Protection incurred by PAI-1 deletion thus appears to be dependent on the model of injury and the type of infection. Furthermore, lung mechanics may be affected differently by PAI-1 deletion in our model in the setting of an additional insult in which PAI-1 is known to be important, such as long-term injurious mechanical ventilation (12,13).…”