Adenosine 2A Receptor Activation Attenuates Ischemia Reperfusion Injury During Extracorporeal Cardiopulmonary Resuscitation

Abstract

Using a novel and clinically relevant porcine model of circulatory arrest and ECPR, we demonstrated that a selective A2AR agonist significantly attenuated systemic IRI and warrants clinical investigation.

Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies

“…They found that IRI to DMECs was significantly attenuated by ischemic postconditioning or agonism of A 2A receptors and, inversely worsened by its antagonism. In agreement, agonism of A 2A receptors can also attenuate IRI in a porcine model of extracorporeal cardiopulmonary resuscitation by lowering the lactate peak after reperfusion, as well as the markers of inflammation and liver and kidney stress [211]. Selective antagonism of A 2A has been, however, frequently shown to achieve protective outcomes [212,213,214].…”

Adenosine A2A receptor agonist (regadenoson) in human lung transplantation

“…16−22 The molecular mechanisms of adenosine-mediated protection in the setting of pulmonary IRI has been extensively studied by our group. 23,24 Lung protection by A 2A R agonists is mediated primarily by suppressing an inflammatory cascade that is initiated by the activation of iNKT cells, 8 as well as by additional effects to inhibit oxidative burst in neutrophils, platelet aggregation, 25 and inflammatory cytokine release from myeloid cells. 26−28 Based on numerous pre-clinical studies by our group and others, we hypothesize that a Food and Drug Administration (FDA)−approved adenosine A 2A R agonist, regadenoson (Lexiscan, Astellas Pharma US, Inc., Northbrook, IL), administered to lung recipients immediately before transplantation will attenuate IRI.…”

Commentary: Planes, trains, and automobiles—Effective use of prolonged ex vivo heart preservation

“…11 Further investigation is warranted to elucidate cellular pathways precipitating functional decline and the potential impact of pharmaceuticals aimed at mitigating ischemia-reperfusion injury. 12,13 It is reassuring to know this technology can support long-distance travel and positive outcomes can be achieved with OCS time greater than 17 h, especially in an organ meeting extended criteria donor status. 6,14 Finally, it cannot be understated how important donor selection is.…”

“…Ex vivo perfusion technology will continue to help with the long‐distance transplant but is still imperfect as evidence in translational models where myocardial function deteriorates over time 11 . Further investigation is warranted to elucidate cellular pathways precipitating functional decline and the potential impact of pharmaceuticals aimed at mitigating ischemia‐reperfusion injury 12,13 . It is reassuring to know this technology can support long‐distance travel and positive outcomes can be achieved with OCS time greater than 17 h, especially in an organ meeting extended criteria donor status 6,14 .…”