Junior Edson Ricardo Brambate, Wang Aizhou, Ribeiro Rafaela Vanin Pinto, Beroncal Erika L, Ramadan Khaled, Michaelsen Vinicius Schenk, Chen Manyin, Ali Aadil, Zhang Yu, Pal Prodipto, Abdelnour Etienne, Siebiger Gabriel, Pinto Bruno Maineri, Waddell Tom, Andreazza Ana C, Keshavjee Shaf, Cypel Marcelo
Latner Thoracic Research Laboratories, Toronto Lung Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Departments of Pharmacology & Toxicology and Psychiatry, Mitochondrial Innovation Initiative, University of Toronto, Toronto, Ontario, Canada.
J Heart Lung Transplant. 2025 May;44(5):780-792. doi: 10.1016/j.healun.2024.09.019. Epub 2024 Oct 4.
Recent clinical series on donation after uncontrolled cardiovascular death (uDCD) reported successful transplantation of lungs preserved by pulmonary inflation up to 3 hours postmortem. 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: control-static lung inflation only (SLI); TC - SLI + continuous intrapleural topical cooling (TC); or TC+Sevo - SLI + TC + sevoflurane. Lungs were retrieved 6 hours postasystole and evaluated via ex vivo lung perfusion (EVLP) for 6 hours. A left single lung transplant was performed using lungs from the best performing group, followed by 4 hours of graft evaluation.
Animals that received TC 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 postpreservation 6 hours EVLP assessment. Despite similar early performance of the 2 groups on EVLP, the TC+Sevo group was superior-associated with overall lower airway pressures, higher pulmonary compliances, less edema development, and less inflammation. Transplantation was performed using lungs from the TC+Sevo group, and excellent graft function was observed postreperfusion.
Preservation of uDCD lungs with a combination of static lung inflation, TC and sevoflurane treatment maintains good pulmonary function up to 6 hours postmortem with excellent early post lung transplant function. These interventions may significantly expand the clinical utilization of uDCD donor lungs.
近期关于非可控性心血管死亡后器官捐献(uDCD)的临床系列报道称,通过肺膨胀保存的肺在死后3小时内成功实现了移植。本研究旨在探讨在猪uDCD模型中,胸腔内原位降温与七氟醚预处理对肺移植供体肺的附加作用。
诱导uDCD后,将供体猪分配至以下组之一:对照组——仅静态肺膨胀(SLI);TC组——SLI + 持续胸膜腔内局部降温(TC);或TC+Sevo组——SLI + TC + 七氟醚。心脏停搏6小时后取出肺脏,并通过离体肺灌注(EVLP)进行6小时评估。使用表现最佳组的肺进行左单肺移植,随后进行4小时的移植肺评估。
接受TC的动物在胸腔填充冷却剂后1小时内胸腔温度降至<15°C。仅接受TC和TC+Sevo的供体的肺完成了计划的保存后6小时EVLP评估。尽管两组在EVLP上的早期表现相似,但TC+Sevo组更优——与总体较低的气道压力、较高的肺顺应性、较少的水肿形成和较少的炎症相关。使用TC+Sevo组的肺进行移植,再灌注后观察到移植肺功能良好。
联合使用静态肺膨胀、TC和七氟醚处理保存uDCD供体肺,可在死后6小时内维持良好的肺功能,并在肺移植后早期具有优异的功能。这些干预措施可能会显著扩大uDCD供体肺的临床应用。