Cardiac-dead mouse lungs may remain transplantable at 37ºC for 4 hours if gas exchange is preserved

Despite a potentially huge number, uncontrolled donation after circulatory death contributed little to alleviating donor lung shortage due to rapidly progressive warm ischemia. Many methods have been studied in animals, but the tolerable warm ischemic time (WIT) remains less than 90 minutes. Using a refined mouse model of pulmonary artery ligation (PAL), we firstly determined the maximum tolerable WIT. 4-hour PAL caused mild lung infiltration without dysfunction upon reperfusion, whereas 5-hour PAL triggered arterial endothelium injury and more significant infiltration with dysfunction. Transcriptional profiling showed a myeloid-dominant inflammation with mild injury in 4-hour PAL. The maximum WIT was then adapted in a clinically relevant scenario. Donor mice died of circulatory arrest without heparization and remained at 37ºC for 4 hours, followed by isogenic transplantation. As observed in 4-hour PAL, nonhypoxic warm ischemia-reperfusion hardly affected graft function and histology, no matter if warm ischemic lung preserved gas exchange by spontaneously breathing or by postmortem protective ventilation. If the dead donors were left untouched, however, the grafted lungs suffered severe hypoxic warm ischemia-reperfusion injury, varying from partially aerated totally lost. Taken together, the retrieval time can be extended to 4 hours at 37ºC by preventing cardiac-dead donor lung hypoxia. Overall design: Transcriptional profiling were performed on three naïve lung samples and three left lung with warm ischemia-reperfusion injury induced by 4 hours of pulmonary artery ligation and 24 hours of reperfusion in adult wild type (WT) B6 mice