Altered Profile of Circulating Endothelial-Derived Microparticles in Ventilator-Induced Lung Injury*. Issue 12 (December 2015)

• Record Type: Journal Article
• Authors: Cabrera-Benítez, Nuria E.; Valladares, Francisco; García-Hernández, Sonia; Ramos-Nuez, Ángela; Martín-Barrasa, José L.; Martínez-Saavedra, María-Teresa; Rodríguez-Gallego, Carlos; Muros, Mercedes; Flores, Carlos; Liu, Mingyao; Slutsky, Arthur S.; Villar, Jesús
• Is Part Of: Critical care medicine. Volume 43:Issue 12(2015)
• Publication Date: 2015-12
• Subjects: acute lung injury -- mechanical ventilation -- platelet-endothelial cell adhesion molecule -- ventilator-induced lung injury; Critical care medicine -- Periodicals; Soins intensifs -- Périodiques; 616.028
• DOI: 10.1097/CCM.0000000000001280
• Languages: English
• ISSNs: 0090-3493

Abstract

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 H2 O 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.