Adenosine A_2A agonist improves lung function during Ex vivo lung perfusion

Background: Ex vivo lung perfusion (EVLP) is a novel technique than can be used to assess and potentially repair marginal lungs that may otherwise be rejected for transplantation. Adenosine has been shown to protect against pulmonary ischemia-reperfusion (IR) injury through its A_2A receptor. We hypothesized that combining EVLP with adenosine A_2A receptor agonist treatment would enhance lung functional quality and increase donor lung use. Methods: Eight bilateral pig lungs were harvested and flushed with cold Perfadex (Vitrolife, Englewood, CO). After 14 hours of storage at 4°C, EVLP was performed for 5 hours on 2 explanted lung groups: (1) control group lungs (n = 4) were perfused with Steen Solution (Vitrolife) and dimethyl sulfoxide and (2) treated group lungs (n = 4) received 10 μM CGS21680, a selective A _2A receptor agonist, in a Steen solutionprimed circuit. Lung histologic features, tissue cytokines, gas analysis, and pulmonary function were compared between groups. Results: Treated lungs demonstrated significantly less edema as reflected by wet-dry weight ratio (6.6 versus 5.2; p < 0.03) and confirmed by histologic examination. In addition, treated lung demonstrated significantly lower levels of interferon-γ (IFN- γ) (45.1 versus 88.5; p < 0.05). Other measured tissue cytokine levels (interleukin [IL]-1β, IL-6, and IL-8) were lower in the treatment group, but values failed to reach statistical significance. The oxygenation index was improved in the treated group (1.5 versus 2.3; p < 0.01) as was mean airway pressure (10.3 versus 13; p < 0.009). Conclusions: Combined use of adenosine A _2A agonist and EVLP significantly attenuates the inflammatory response in acutely injured lungs after IR and enhances pulmonary function. This combination may improve donor lung quality and could increase the donor lung pool for transplantation.