Protective effects of adenosine A2A receptor agonist in ventilator-induced lung injury in rats

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 A(2A) receptors has been reported to attenuate inflammatory cascades. Hypothesis. The administration of A(2A) 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 A(2A) 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 A(2A) receptor agonist may have a place as a novel therapeutic approach in reducing VILI. (Crit Care Med 2009; 37:2235-2241)