Uncontrolled donation after cardiac death (uDCD) contributes little to ameliorating donor lung shortage due to rapidly progressive warm ischemia after circulatory arrest. Here, we demonstrated non-hypoxia improves donor lung viability in a novel uDCD lung transplant model undergoing rapid ventilation after cardiac death and compared the evolution of ischemia-reperfusion injury in mice that underwent pulmonary artery ligation (PAL). The tolerable warm ischemia time at 37ºC was initially determined in mice using a modified PAL model. The donor lung following PAL was also transplanted into syngeneic mice and compared to those that underwent rapid ventilation or no ventilation at 37ºC prior to transplantation. Twenty-four hours following reperfusion, lung histology, PaO2/FIO2 ratio, and inflammatory mediators were measured. Four hours of PAL had little impact on PaO2/FIO2 ratio and acute lung injury score in contrast to significant injury induced by 5 hours of PAL. Four-hour PAL lungs showed an early myeloid-dominant inflammatory signature when compared to naïve lungs and substantially injured five-hour PAL lungs. In the context of transplantation, unventilated donor lungs showed severe injury after reperfusion, whereas ventilated donor lungs showed minimal changes in PaO2/FIO2 ratio, histologic score, and expression of inflammatory markers. Taken together, the tolerable warm ischemia time of murine lungs at 37^oC can be extended by maintaining alveolar ventilation for up to 4 hours. Non-hypoxic lung warm ischemia-reperfusion injury shows an early transcriptional signature of myeloid cell recruitment and extracellular matrix proteolysis prior to blood-gas barrier dysfunction and significant tissue damage.

中文翻译：

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快速死后通气通过延长小鼠心脏死亡后可耐受的热缺血时间来提高供体肺活力

由于循环停止后迅速进行性热缺血，心脏死亡后不受控制的捐赠 (uDCD) 对改善供体肺短缺几乎没有贡献。在这里，我们证明了在心脏死亡后进行快速通气的新型 uDCD 肺移植模型中，非缺氧提高了供体肺活力，并比较了接受肺动脉结扎 (PAL) 的小鼠缺血再灌注损伤的演变。37ºC 下可耐受的热缺血时间最初是使用改良的 PAL 模型在小鼠中确定的。PAL 后的供体肺也被移植到同基因小鼠中，并与移植前在 37ºC 下进行快速通气或不通气的小鼠进行比较。再灌注后 24 小时，测量肺组织学、PaO2/FIO2 比值和炎症介质。与 5 小时 PAL 引起的显着损伤相比，4 小时 PAL 对 PaO2/FIO2 比值和急性肺损伤评分几乎没有影响。与幼稚肺和严重受损的 5 小时 PAL 肺相比，4 小时 PAL 肺显示出早期骨髓为主的炎症特征。在移植的背景下，未通气的供体肺在再灌注后表现出严重的损伤，而通气的供体肺在 PaO2/FIO2 比值、组织学评分和炎症标志物的表达方面的变化很小。综上所述，小鼠肺在 37 岁时可耐受的热缺血时间 与幼稚肺和严重受损的 5 小时 PAL 肺相比，4 小时 PAL 肺显示早期髓系主导炎症特征。在移植的背景下，未通气的供体肺在再灌注后表现出严重的损伤，而通气的供体肺在 PaO2/FIO2 比值、组织学评分和炎症标志物的表达方面表现出最小的变化。综上所述，小鼠肺在 37 岁时可耐受的热缺血时间 与幼稚肺和严重受损的 5 小时 PAL 肺相比，4 小时 PAL 肺显示早期髓系主导炎症特征。在移植的背景下，未通气的供体肺在再灌注后表现出严重的损伤，而通气的供体肺在 PaO2/FIO2 比值、组织学评分和炎症标志物的表达方面表现出最小的变化。综上所述，小鼠肺在 37 岁时可耐受的热缺血时间^o C 可以通过保持肺泡通气长达 4 小时来延长。非缺氧性肺热缺血-再灌注损伤在血气屏障功能障碍和显着组织损伤之前显示出髓细胞募集和细胞外基质蛋白水解的早期转录特征。