Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, 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. 2022 Dec;41(12):1679-1688. doi: 10.1016/j.healun.2022.08.025. Epub 2022 Sep 8.
Our recent work has challenged 4°C as an optimal lung preservation temperature by showing storage at 10°C to allow for the extension of preservation periods. Despite these findings, the impact of 10°C storage has not been evaluated in the setting of injured donor lungs.
Aspiration injury was created through bronchoscopic delivery of gastric juice (pH: 1.8). Injured donor lungs (n = 5/group) were then procured and blindly randomized to storage at 4°C (on ice) or at 10°C (in a thermoelectric cooler) for 12 hours. A third group included immediate transplantation. A left lung transplant was performed thereafter followed by 4 hours of graft evaluation.
After transplantation, lungs stored at 10°C showed significantly better oxygenation when compared to 4°C group (343 ± 43 mm Hg vs 128 ± 76 mm Hg, p = 0.03). Active metabolism occurred during the 12 hours storage period at 10°C, producing cytoprotective metabolites within the graft. When compared to lungs undergoing immediate transplant, lungs preserved at 10°C tended to have lower peak airway pressures (p = 0.15) and higher dynamic lung compliances (p = 0.09). Circulating cell-free mitochondrial DNA within the recipient plasma was significantly lower for lungs stored at 10°C in comparison to those underwent immediate transplant (p = 0.048), alongside a tendency of lower levels of tissue apoptotic cell death (p = 0.075).
We demonstrate 10°C as a potentially superior storage temperature for injured donor lungs in a pig model when compared to the current clinical standard (4°C) and immediate transplantation. Continuing protective metabolism at 10°C for donor lungs may result in better transplant outcomes.
我们最近的研究挑战了 4°C 作为肺最佳保存温度的观点,表明在 10°C 下储存可以延长保存时间。尽管有这些发现,但在受伤供肺的情况下,10°C 储存的影响尚未得到评估。
通过支气管镜给予胃液(pH:1.8)来造成吸入性损伤。然后获取受伤的供肺(每组 n=5),并在 4°C(冰上)或 10°C(热电冷却器中)下盲目随机储存 12 小时。第三组包括立即移植。之后进行左肺移植,然后进行 4 小时的移植物评估。
移植后,与 4°C 组相比,10°C 储存的肺显示出明显更好的氧合作用(343 ± 43 mm Hg 比 128 ± 76 mm Hg,p=0.03)。在 10°C 储存期间,主动代谢发生,在移植物内产生细胞保护代谢物。与立即移植的肺相比,10°C 保存的肺在峰值气道压力方面有降低的趋势(p=0.15),动态肺顺应性更高(p=0.09)。与立即移植的肺相比,10°C 储存的肺在受体血浆中的循环无细胞线粒体 DNA 明显降低(p=0.048),同时组织细胞凋亡死亡水平也有降低的趋势(p=0.075)。
我们在猪模型中证明,与当前的临床标准(4°C)和立即移植相比,10°C 是一种更适合受伤供肺的潜在储存温度。在 10°C 下继续对供肺进行保护性代谢可能会导致更好的移植结果。