Abstract
OBJECTIVES: Mechanical ventilation is associated with overwhelming 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 H2O. 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.