Abstract
To investigate the anti-inflammatory effects of simvastatin in rats undergoing one-lung ventilation (OLV) followed by lung re-expansion. Male Wistar rats (n=30) were submitted to 1-h OLV followed by 1-h lung re-expansion. Treated group received simvastatin (40 mg/kg for 21 days) previous to OLV protocol. Control group received no treatment or surgical/ventilation interventions. Measurements of pulmonary myeloperoxidase (MPO) activity, pulmonary protein extravasation, and serum levels of cytokines and C-reactive protein (CRP) were performed. OLV significantly increased the MPO activity in the collapsed and continuously ventilated lungs (31% and 52% increase, respectively) compared with control (p<0.05). Treatment with simvastatin significantly reduced the MPO activity in the continuously ventilated lung but had no effect on lung edema after OLV. The serum IL-6 and CRP levels were markedly higher in OLV group, but simvastatin treatment failed to affect the production of these inflammatory markers. Serum levels of IL-1β, TNF-α and IL-10 remained below the detection limit in all groups. In an experimental one-lung ventilation model pre-operative treatment with simvastatin reduces remote neutrophil infiltration in the continuously ventilated lung. Our findings suggest that simvastatin may be of therapeutic value in OLV-induced pulmonary inflammation deserving clinical investigations.
Highlights
The one-lung ventilation (OLV), a ventilation strategy used during thoracic surgery, consists in an intentional and temporary collapse of a lung[1], while the other one remains normally ventilated
We have investigated the beneficial effects of simvastatin in rats undergoing OLV followed by lung reexpansion[10], evaluating the pulmonary and systemic inflammatory processes, as well as hemodynamic and gasometric parameters
Measurement of MPO activity was performed in the right and left lungs of rats from the control, OLV and OLV+Simv groups
Summary
The one-lung ventilation (OLV), a ventilation strategy used during thoracic surgery, consists in an intentional and temporary collapse of a lung[1], while the other one remains normally ventilated. This ventilator strategy initiates a series of pathophysiologic events that can be attributed to two major factors, namely hypoxia and re-oxygenation. OLV in animals has been accepted as an ideal model to produce lung injury associated with organ failure and high mortality levels[3]. Some pharmacological treatments aiming suppress the acute lung injury or acute respiratory distress syndrome has been used, many specific therapies have not proved beneficial, such as mortality reduction[4]
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