Adenosine Receptor Activation During Extracorporeal Cardiopulmonary Resuscitation Improves Survival After Cardiac Arrest in Swine

Introduction: Despite advances in resuscitation protocols, including the addition of Extracorporeal Cardiopulmonary Resuscitation (ECPR), survival after cardiac arrest remains less than 40% and novel methods are needed to attenuate global injury and improve outcomes. ATL1223, an adenosine 2A receptor (A2AR) agonist has been shown to attenuate organ specific reperfusion injury by modulating the interaction of inflammatory cells. Hypothesis: A2AR activation during ECPR will improve survival and decrease the burden of injury in a large animal model of cardiac arrest. Methods: Adult swine underwent 20 minutes of circulatory arrest followed by defibrillation and 6 hours of ECPR. Animals were randomized to receive saline control (n=5) or the A2AR agonist Regadenoson (0.144 and 14.4mcg/kg/hr, n=5/group). Animals were subsequently weaned from ECPR and monitored for 24 hours. Clinical and biochemical endpoints were compared between groups. Results: The administration of Regadenoson increased survival after cardiac arrest compared to saline controls (10/10, 100% vs 2/5, 40%, p=0.02, Figure 1). Anesthetic administration (p=0.41), fluid resuscitation (p=0.54), and epinephrine required to maintain target arterial pressure (p=0.08) were similar for all subjects. Biochemical markers of organ damage, including creatinine (p=0.87), aspartate aminotransferase (p=0.89), and troponin I (p=0.38), were similar among groups (Figure 2). Conclusions: In a clinically relevant model of cardiac arrest treated with ECPR, selective A2AR agonism increased survival from 40% to 100% at 24 hours. These results suggest A2AR activation is a promising therapeutic target after cardiac arrest.