title: 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 (n = 61) 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.
authors.affiliation: Dept of Anaesthesiology, Erasmus MC-Faculty Rotterdam, Rotterdam, Amsterdam. PDahlem@hotmail.com
authors.forename: P
authors.initials: P
authors.lastname: Dahlem
authors.forename: A P
authors.initials: AP
authors.lastname: Bos
authors.forename: J J
authors.initials: JJ
authors.lastname: Haitsma
authors.forename: M J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: E K
authors.initials: EK
authors.lastname: Wolthuis
authors.forename: J C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: B
authors.initials: B
authors.lastname: Lachmann
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D005342:Fibrinolysis / Q000502:physiology*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D011650:Pulmonary Alveoli / Q000293:injuries* / Q000378:metabolism / Q000382:microbiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000503:physiopathology; D012477:Salmonella enteritidis / Q000472:pathogenicity*
chemical_list: D008070:Lipopolysaccharides