Altered Profile of Circulating Endothelial-Derived Microparticles in Ventilator-Induced Lung Injury

作者：Cabrera Benitez Nuria E; Valladares Francisco; Garcia Hernandez Sonia; Ramos Nuez Angela; Martin Barrasa Jose L; Martinez Saavedra Maria Teresa; Rodriguez Gallego Carlos; Muros Mercedes; Flores Carlos; Liu Mingyao; Slutsky Arthur S; Villar Jesus^*

来源：Critical Care Medicine, 2015, 43(12): E551-E559.

DOI：10.1097/CCM.0000000000001280

• acute lung injury
• mechanical ventilation
• platelet-endothelial cell adhesion molecule
• ventilator-induced lung injury

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.

• 出版日期2015-12
• 单位河北医科大学