BackgroundRecent clinical series on donation after uncontrolled cardiovascular death (uDCD) reported successful transplantation of lungs preserved by pulmonary inflation up to 3h post-mortem. This study aims to investigate the additive effects of in situ lowering of intrathoracic temperature and sevoflurane preconditioning on lung grafts in a porcine uDCD model. MethodsAfter uDCD induction, donor pigs were allocated to one of the following groups: Control – static lung inflation only (SLI); TC – SLI + continuous intrapleural topical cooling (TC); or TC+Sevo – SLI + TC + sevoflurane. Lungs were retrieved 6h post-asystole and evaluated via ex vivo lung perfusion (EVLP) for 6h. A left single lung transplant was performed using lungs from the best performing group, followed by 4h of graft evaluation. ResultsAnimals that received topical cooling achieved intrathoracic temperature < 15°C within 1 hour after chest filling of coolant. Only lungs from donors that received TC and TC+Sevo completed the planned post-preservation 6h EVLP assessment. Despite similar early performance of the two groups on EVLP, the TC+Sevo group was superior - associated with overall lower airway pressures, higher pulmonary compliances, less edema development, and less release of inflammatory cytokines. Transplantation was performed using lungs from the TC+Sevo group, and excellent graft function was observed post-reperfusion. ConclusionPreservation of uDCD lungs with a combination of static lung inflation, topical cooling and sevoflurane treatment maintains good pulmonary function up to 6h post-mortem with excellent early post-lung transplant function. These interventions may significantly expand the clinical utilization of uDCD donor lungs.