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  • Title: Altered Profile of Circulating Endothelial-Derived Microparticles in Ventilator-Induced Lung Injury.
    Author: Cabrera-Benítez NE, Valladares F, García-Hernández S, Ramos-Nuez Á, Martín-Barrasa JL, Martínez-Saavedra MT, Rodríguez-Gallego C, Muros M, Flores C, Liu M, Slutsky AS, Villar J.
    Journal: Crit Care Med; 2015 Dec; 43(12):e551-9. PubMed ID: 26308427.
    Abstract:
    OBJECTIVES: Pulmonary endothelial cell injury is central to the pathophysiology of acute lung injury. Mechanical ventilation can cause endothelial disruption and injury, even in the absence of preexisting inflammation. Platelet-endothelial cell adhesion molecule-1 is a transmembrane protein connecting adjacent endothelial cells. We hypothesized that injurious mechanical ventilation will increase circulating lung endothelial-derived microparticles, defined as microparticles positive for platelet-endothelial cell adhesion molecule-1, which could serve as potential biomarkers and mediators of ventilator-induced lung injury. DESIGN: Prospective randomized, controlled, animal investigation. SETTING: A hospital preclinical animal laboratory. SUBJECTS: Forty-eight Sprague-Dawley rats. INTERVENTIONS: Animals were randomly allocated to one of the three following ventilatory protocols for 4 hours: spontaneous breathing (control group), mechanical ventilation with low tidal volume (6 mL/kg), and mechanical ventilation with high tidal volume (20 mL/kg). In both mechanical ventilation groups, positive end-expiratory pressure of 2 cm H2O was applied. MEASUREMENTS AND MAIN RESULTS: We analyzed histologic lung damage, gas exchange, wet-to-dry lung weight ratio, serum cytokines levels, circulating endothelial-derived microparticles, platelet-endothelial cell adhesion molecule-1 lung protein content, and immunohistochemistry. When compared with low-tidal volume mechanical ventilation, high-tidal volume ventilation increased lung edema score and caused gas-exchange deterioration. These changes were associated with a marked increased of circulating endothelial-derived microparticles and a reduction of platelet-endothelial cell adhesion molecule-1 protein levels in the high-tidal volume lungs (p < 0.0001). CONCLUSIONS: There is an endothelial-derived microparticle profile associated with disease-specific features of ventilator-induced lung injury. This profile could serve both as a biomarker of acute lung injury and, potentially, as a mediator of systemic propagation of pulmonary inflammatory response.
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