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

Abstract

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. Prospective randomized, controlled, animal investigation. A hospital preclinical animal laboratory. Forty-eight Sprague-Dawley rats. 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. 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). 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.