Rapid postmortem ventilation improves donor lung viability by extending the tolerable warm ischemic time after cardiac death in mice

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 that nonhypoxia 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 to mice that underwent pulmonary artery ligation (PAL). The tolerable warm ischemia time at 37 degrees C was initially determined in mice using a modified PAL model. The donor lung following PAL was also transplanted into syngeneic mice and compared with those that underwent rapid ventilation or no ventilation at 37 degrees C before transplantation. Twenty-four hours following reperfusion, lung histology, Pa-o2/Fi(o2), ratio, and inflammatory mediators were measured. Four hours of PAL had little impact on Pa-o2/Fi(o2) ratio and acute lung injury score in contrast to significant injury induced by 5 h of PAL. Four-hour PAL lungs showed an early myeloid-dominant inflammatory signature when compared with naive lungs and substantially injured 5 h PAL lungs. In the context of transplantation, unventilated donor lungs showed severe injury after reperfusion, whereas ventilated donor lungs showed minimal changes in Pa-o2/Fi(o2), ratio, histologic score, and expression of inflammatory markers. Taken together, the tolerable warm ischemia time of murine lungs at 37 degrees C can be extended by maintaining alveolar ventilation for up to 4 h. Nonhypoxic lung undergoing warm ischemia-reperfusion injury shows an early transcriptional signature of myeloid cell recruitment and extracellular matrix proteolysis before blood-gas barrier dysfunction and significant tissue damage.

Automated summary

Maintaining alveolar ventilation can extend the tolerable warm ischemia time of murine lungs at 37 degrees Celsius up to 4 hours. Nonhypoxic lungs undergoing warm ischemia-reperfusion injury exhibit early transcriptional signatures of myeloid cell recruitment and extracellular matrix proteolysis before the dysfunction of blood-gas barrier and significant tissue damage occur.