Inflammatory responses in lungs from donation after brain death: Mechanisms and potential therapeutic targets

Abstract

The vast majority of lungs used in clinical transplantation are donated after brain death (DBD). The utilization of DBD lungs is low due to brain death-induced lung injury. Moreover, inflammatory responses in DBD lungs used for transplantation contribute to ischemia-reperfusion injury and primary graft dysfunction. Work from human observational studies has demonstrated overexpression of cytokines, activation of endothelial cells, and cell death in DBD lungs, are associated with the activation of signaling pathways. Animal models have characterized the pulmonary injury induced by brain death and identified potential strategies to improve donor management. Interestingly, transcriptomic studies comparing DBD and donated after circulatory death (DCD) lungs have found that inflammatory responses are elevated in DBD lungs, while cell death pathways are elevated in DCD lungs. Development of the ex vivo lung perfusion technique, has made it possible to assess donor lungs using inflammation and cell death biomarkers. In the future, identification of potential therapeutic targets and development of novel treatments strategies may allow for lung repair during EVLP prior to transplantation.

Keywords: brain death; cell death; donation after circulatory death; inflammation; ischemia-reperfusion.