Adenosine A2A receptor activation reduces lung injury in trauma/hemorrhagic shock*

Abstract

A(2A) receptor agonists may represent a novel therapeutic approach in preventing organ injury following trauma/hemorrhagic shock.

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

“…In ischemia reperfusion models, the use of A 2A receptor agonists resulted in a decrease in macrophage activation and adhesion molecular expression on endothelial cells, blockage of endothelial-neutrophil interactions, and attenuation of vascular derangement (11,12,(17)(18)(19)(20)(21). The administration of the A 2A receptors agonist CGS-21680 has been shown to ameliorate lung injury in animal models of ischemia and reperfusion (12,17). Furthermore, a reduced inflammatory response and preserved pulmonary function was achieved by using an A 2A receptor agonist in a rabbit model of lung transplantation (18).…”

“…Our HSR model is different from those ischemia reperfusion models previously described (12,17). We used a shorter period of reperfusion (30 minutes) than the previous models in which a longer time of reperfusion (3 hours) was used (12,17,18).…”

“…We used a shorter period of reperfusion (30 minutes) than the previous models in which a longer time of reperfusion (3 hours) was used (12,17,18). Thus, an inflammatory response was induced by HSR to prime the lung without causing lung injury in our rat model (18).…”

“…Adenosine-a purine nucleoside released during hypoxia, inflammation, and ischemia/ reperfusion-is a potent agent to protect organ systems from injury by its anti-inflammatory properties (6 -10) to decrease macrophage activation, block endothelial polymorphonuclear neutrophils interactions, and reduce polymorphonuclear neutrophils-mediated injury and vascular derangement (11,12). A couple of recent studies have demonstrated that mechanical ventilation in rats and mice increases the level of pulmonary adenosine (13,14), and that mice deficient for extracellular adenosine generation show increased pulmonary edema and inflammation after VILI (14).…”

Non-Cardiogenic Pulmonary Edema

“…It has also been well documented that the percentage of neutrophils correlates directly with the alveolar-arterial PO2 difference in ALI/ARDS pulmonary edema . Neutrophil sequestration is aided by chemotactic factors and by the adhesion molecules on both the neutrophils and capillary endothelial cells (Hasko et al, 2006;Steinberg, 1994;Geerts et al, 2001). The activated neutrophils expressing IL-1 produce other pro-inflammatory cytokines after endotoxin administration.…”