Adenosine A_2A Activation Attenuates Nontransplantation Lung Reperfusion Injury

Background: Lung reperfusion injury is a significant problem in cardiothoracic surgery. Previous studies have demonstrated that an adenosine A_2A agonist can attenuate lung reperfusion injury in a lung transplantation model. There has been little work, however, examining its effects in the setting of nontransplant ischemia reperfusion. Our hypothesis was that an A_2A agonist would attenuate lung reperfusion injury in a warm ischemia hilar clamping model. Study design: Sprague Dawley rats underwent 90 min of left hilar clamping followed by 4 h of reperfusion. Group 1 (n = 13) received an intravenous infusion of 0.06 ug/kg/min of ATL-146e, which was started 10 min before reperfusion. Group 2 (n = 16) received an equivalent saline infusion. A third sham group (n = 14) received the same protocol as Group 2 but no lung ischemia. Results: Animals receiving ATL-146e showed significant improvements in oxygenation (Group 1: 447 ± 26.02 mmHg versus Group 2: 223 ± 24.46 mmHg (P < 0.001) as well as ventilation (pCO2 Group 1: 48.78 ± 3.88 versus Group 2: 63.56 ± 4.80 (P = 0.009)). Total protein in the bronchoalveolar lavage was significantly higher in the saline group compared with the adenosine as well as a higher proportion of neutrophils. Histological analysis demonstrated a significantly higher number of neutrophils in the IR group compared with the adenosine group. Conclusions: ATL-146e, an adenosine analogue that is a specific agonist for the A_2A receptor, attenuates reperfusion injury in an in vivo rat lung model. Arterial blood gas measurements demonstrate a statistically significant increase in oxygenation and improved ventilation.