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


OBJECTIVE
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.
Chen
Chin-Ming
CM
Department of Intensive Care Medicine and Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Penuelas
Oscar
O
Quinn
Kieran
K
Cheng
Kuo-Chen
KC
Li
Chien-Feng
CF
Zhang
Haibo
H
Slutsky
Arthur S
AS
D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D008297:Male; D010627:Phenethylamines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D015656:Respiratory Mechanics; D012771:Shock, Hemorrhagic / Q000209:etiology / Q000517:prevention & control*; D055397:Ventilator-Induced Lung Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D058908:Adenosine A2 Receptor Agonists; D016207:Cytokines; D010627:Phenethylamines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine