Cold static preservation on ice (~4°C) remains the clinical standard of donor organ preservation. However, mitochondrial injury develops during prolonged storage, which limits the extent of time that organs can maintain viability. We explored the feasibility of prolonged donor lung storage at 10°C using a large animal model and investigated mechanisms related to mitochondrial protection. Functional assessments performed during ex vivo lung perfusion demonstrated that porcine lungs stored for 36 hours at 10°C had lower airway pressures, higher lung compliances, and better oxygenation capabilities, indicative of better pulmonary physiology, as compared to lungs stored conventionally at 4°C. Mitochondrial protective metabolites including itaconate, glutamine, and N-acetylglutamine were present in greater intensities in lungs stored at 10°C than at 4°C. Analysis of mitochondrial injury markers further confirmed that 10°C storage resulted in greater protection of mitochondrial health. We applied this strategy clinically to prolong preservation of human donor lungs beyond the currently accepted clinical preservation limit of about 6 to 8 hours. Five patients received donor lung transplants after a median preservation time of 10.4 hours (9.92 to 14.8 hours) for the first implanted lung and 12.1 hours (10.9 to 16.5 hours) for the second. All have survived the first 30 days after transplantation. There was no grade 3 primary graft dysfunction at 72 hours after transplantation, and median post-transplant mechanical ventilation time was 1.73 days (0.24 to 6.71 days). Preservation at 10°C could become the standard of care for prolonged pulmonary preservation, providing benefits to both patients and health care teams.

中文翻译：

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10°C 的静态肺储存可维持线粒体健康并保留供体器官功能

冰上冷静态保存（~4°C）仍然是供体器官保存的临床标准。然而，线粒体损伤会在长期储存期间发生，这限制了器官维持活力的时间范围。我们使用大型动物模型探索了在 10°C 下延长供体肺储存的可行性，并研究了与线粒体保护相关的机制。在离体肺灌注期间进行的功能评估表明，与在 4°C 下常规储存的肺相比，在 10°C 下储存 36 小时的猪肺具有更低的气道压力、更高的肺顺应性和更好的氧合能力，表明肺生理学更好. 线粒体保护性代谢物，包括衣康酸、谷氨酰胺和N-乙酰谷氨酰胺在 10°C 储存的肺中比 4°C 储存的强度更高。线粒体损伤标志物的分析进一步证实，10°C 储存可更好地保护线粒体健康。我们在临床上应用这种策略来延长人类供体肺的保存时间，超过目前公认的临床保存时间约 6 至 8 小时。5 名患者在第一个移植肺的中位保存时间为 10.4 小时（9.92 至 14.8 小时）和第二个移植肺的中位保存时间为 12.1 小时（10.9 至 16.5 小时）后接受了供体肺移植。所有人都在移植后的前 30 天存活下来。移植后72小时未发生3级原发性移植物功能障碍，移植后机械通气时间中位数为1.73天（0.24～6.71天）。