Objectives: Mechanical ventilation is associated with over-whelming inflammatory responses that are associated with ventilator-induced lung injury (VILI) in patients with acute respiratory distress syndrome. The activation of adenosine A2A receptors has been reported to attenuate inflammatory cascades. Hypothesis: The administration of A2A receptors agonist ameliorates VILI. Methods: Rats were subjected to hemorrhagic shock and resuscitation as a first hit to induce systemic inflammation. The animals randomly received the selective A2A receptor agonist CGS-21680 or a vehicle control in a blinded fashion at the onset of resuscitation phase. They were then randomized to receive mechanical ventilation as a second hit with a high tidal volume of 20 mL/kg and zero positive end-expiratory pressure, or a low tidal volume of 6 mL/kg with positive end-expiratory pressure of 5 cm H 2O. Results: The administration of CGS-21680 attenuated lung injury as evidenced by a decrease in respiratory elastance, lung edema, lung injury scores, neutrophil recruitment in the lung, and production of inflammatory cytokines, compared with the vehicle-treated animals. Conclusions: The selective A2A receptor agonist may have a place as a novel therapeutic approach in reducing VILI.
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