(370) - Prolonged Warm Ischemia Prevents Lung Allograft Acceptance in Lung Transplantation from Donation after Cardiac Death in the Mouse

Abstract

s S143 investigated the role of Cyclosporine A (CyA) which is well known as an immunosuppressant drug, in prohibiting mitochondrial permeability transition and subsequent proinflammatory changes in lung grafts, leading to their improved graft quality on EVLP. Methods: Using rat heart-lung blocks after 1 hour cold preservation, an acellular normothermic EVLP system was established for 4 hours. CyA was added into perfusate for 1 μ M as final content. The evaluation included the routine lung graft function, compliance (Cdyn), and vascular resistance (PVR) as well as biochemical markers in the perfusate at multiple time points. After 4 hours EVLP, their proinflammatory and metabolic profiles were also assessed in lung grafts, including tissue ATP levels, mitochondrial biogenesis and hypoxia inducible factor (HIF)-1α expressions. Results: Lung grafts on EVLP with CyA exhibited significantly better functional and physiological parameters as compared to those without CyA (Fig.1A). CyA administration attenuated proinflammatory changes (Fig.1B) and prohibited glucose consumption during EVLP through mitigating mitochondrial dysfunction and promoting mitochondrial biogenesis in lung grafts (Fig.1C). CyA-treated lungs exhibited significantly attenuated expression of HIF-1α . Conclusion: CyA can be a potent contributor to better preconditioning lung grafts by protecting mitochondrial function during EVLP.