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

Chin Ming Chen, Oscar Penuelas, Kieran Quinn, Kuo Chen Cheng, Chien Feng Li, Haibo Zhang, Arthur S. Slutsky

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Abstract

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.

Original languageEnglish
Pages (from-to)2235-2241
Number of pages7
JournalCritical Care Medicine
Volume37
Issue number7
DOIs
Publication statusPublished - Jul 2009

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Keywords

  • Acute Respiratory distress syndrome
  • Inflammation
  • Neutrophils

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Chen, C. M., Penuelas, O., Quinn, K., Cheng, K. C., Li, C. F., Zhang, H., & Slutsky, A. S. (2009). Protective effects of adenosine A2A receptor agonist in ventilator-induced lung injury in rats. Critical Care Medicine, 37(7), 2235-2241. https://doi.org/10.1097/CCM.0b013e3181a55273