(505) - Relationship between Grafts’ Quality, Glucose Consumption and IL-6 Production during Ex Vivo Lung Perfusion

Abstract

The clustering of ischemia, hypoxia, and proinflammatory changes in transplanted lungs facilitate fibrosis, leading to bronchiolitis obliterans syndrome (BOS) following lung transplantation. We hypothesized this clustering can be underlying mechanism for cellular damage in lung grafts during ex vivo lung perfusion (EVLP) and investigated their correlation among suboptimal blood supply without bronchial circulation, high glucose consumption due to tissue hypoxia, and proinflammatory cytokine production in relation to lung graft function on EVLP. Using rat heart-lung blocks after 1 hour cold preservation, an acellular normothermic EVLP system was established for 4 hours. The evaluation included lung graft function, lung compliance (Cdyn), and vascular resistance (PVR) as well as circulating glucose, lactate and other biochemical markers in the perfusate. The main finding in this study was a strong positive correlation between glucose consumption during EVLP and perfusate IL-6 levels during EVLP (Fig.1A). Glucose consumption also had a positive correlation with the changes in Cdyn and PVR during EVLP. Interestingly, the lungs with higher glucose consumption above 40 mg/dl had significantly higher PVR and lower Cdyn as compared with those with lower glucose consumption below 40 mg/dl (Fig.1B). Higher glucose consumption noted in lung grafts during EVLP represent underlying tissue hypoxia which can augment proinflammatory changes, leading to compromised lung graft quality. This focus may help move forward the strategy using EVLP ultimately to contribute to improving transplant outcomes.