• György Haskó, Da-Zhong Xu, Qi Lu, Zoltán H Németh, Jondavid Jabush, Tamara L Berezina, Sergey B Zaets, Balázs Csóka, and Edwin A Deitch.
• Department of Surgery, UMDNJ-New Jersey Medical School, Newark, USA.
• Crit. Care Med. 2006 Apr 1; 34 (4): 1119-25.

ObjectiveHemorrhagic shock and resuscitation trigger a global ischemia/reperfusion phenomenon, in which various inflammatory processes critically contribute to the ensuing tissue damage. Adenosine is an endogenous nucleoside that is released during shock. Activation of adenosine A(2A) receptors can broadly inactivate inflammatory cascades. The current study was designed to evaluate the effect of A(2A) receptor activation on organ injury and inflammation in the setting of global ischemia/reperfusion elicited by trauma/hemorrhagic shock and resuscitation.DesignProspective animal study with concurrent control.SettingSmall animal laboratory.SubjectsAdult male Sprague-Dawley rats.InterventionsThe rats were subjected to a laparotomy (trauma) and 90 mins of hemorrhagic shock or trauma/sham shock. The selective A(2A) receptor agonist CGS-21680 (2-p-(2-carboxyethyl) phenethylamino-5'-N-ethyl-carboxamidoadenosine; 0.5 mg/kg) or its vehicle was injected 30 mins before shock or immediately after resuscitation. At 3 hrs following resuscitation, animals were killed and tissue was harvested for analysis. Lung permeability and pulmonary myeloperoxidase levels were used to quantitate lung injury. Intestinal injury was determined by histologic analysis of terminal ileum. Red blood cell deformability was measured by a laser-assisted ektacytometer. In this assay, a decrease in the elongation index is a marker of decreased red blood cell deformability.Measurements And Main ResultsPretreatment with CGS-21680 protected the lung but not the gut against shock-induced injury and prevented the shock-induced decrease in red blood cell deformability. Posttreatment with CGS-21680 ameliorated shock-induced lung injury but failed to prevent gut injury and preserve red blood cell deformability.ConclusionA(2A) receptor agonists may represent a novel therapeutic approach in preventing organ injury following trauma/hemorrhagic shock.

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