The Combination of Post-Mortem Sevoflurane Ventilation and In Situ Topical Cooling Provides Improved 6h Lung Preservation in an Uncontrolled DCD Porcine Model

Abstract

Purpose Recent clinical series on donation after uncontrolled cardiac 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. Methods After uDCD induction, donor pigs were allocated to one of the following groups: (1) static lung inflation only (SLI); (2) SLI + continuous intrapleural topical cooling (TC); or (3) sevoflurane preconditioning (30 min) + SLI + TC. Six hours post-asystole, lungs were retrieved and evaluated via ex vivo lung perfusion (EVLP) for 6 hours. The group with best performance on EVLP was then evaluated by transplantation in the 2nd phase of the study. Grafts were reperfused for 4h, followed by right pulmonary hilar clamping to evaluate graft oxygenation and ventilatory mechanics. Results A target intrathoracic temperature < 15°C was achieved within 1 hour of chest filling in groups 2 and 3. All lungs in group 1 failed - i.e., met EVLP termination criteria in 1h (Fig.1A). At 1h lungs from group 3 presented lower PVR, lower airway pressures, higher compliances and a higher P/F ratio compared to group 1 (Fig.1B). Despite similar early performance of groups 2 and 3, group 3 showed lower airway pressures and higher pulmonary compliances at the final hour (Fig.1C). Post-EVLP lung weight (edema) was higher in group 1 compared to groups 2 and 3 (Fig.1B). Post-transplant graft assessment in group 3 showed good oxygenation throughout the post-reperfusion observation period (Fig.1D). Conclusion Preservation of uDCD lungs with sevoflurane + static lung inflation + topical cooling maintains good pulmonary function up to 6h post-mortem with excellent early post-lung transplant function. These interventions could potentially help expand the clinical utilization of uDCD donor lungs for transplantation. Recent clinical series on donation after uncontrolled cardiac 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. After uDCD induction, donor pigs were allocated to one of the following groups: (1) static lung inflation only (SLI); (2) SLI + continuous intrapleural topical cooling (TC); or (3) sevoflurane preconditioning (30 min) + SLI + TC. Six hours post-asystole, lungs were retrieved and evaluated via ex vivo lung perfusion (EVLP) for 6 hours. The group with best performance on EVLP was then evaluated by transplantation in the 2nd phase of the study. Grafts were reperfused for 4h, followed by right pulmonary hilar clamping to evaluate graft oxygenation and ventilatory mechanics. A target intrathoracic temperature < 15°C was achieved within 1 hour of chest filling in groups 2 and 3. All lungs in group 1 failed - i.e., met EVLP termination criteria in 1h (Fig.1A). At 1h lungs from group 3 presented lower PVR, lower airway pressures, higher compliances and a higher P/F ratio compared to group 1 (Fig.1B). Despite similar early performance of groups 2 and 3, group 3 showed lower airway pressures and higher pulmonary compliances at the final hour (Fig.1C). Post-EVLP lung weight (edema) was higher in group 1 compared to groups 2 and 3 (Fig.1B). Post-transplant graft assessment in group 3 showed good oxygenation throughout the post-reperfusion observation period (Fig.1D). Preservation of uDCD lungs with sevoflurane + static lung inflation + topical cooling maintains good pulmonary function up to 6h post-mortem with excellent early post-lung transplant function. These interventions could potentially help expand the clinical utilization of uDCD donor lungs for transplantation.