A Whole-body Cooling Strategy in Uncontrolled Donation After Circulatory Death: Insights From a Porcine Ex Vivo Lung Perfusion Model

循环死亡后非控制性捐献中的全身冷却策略:来自猪离体肺灌注模型的启示

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作者:Hiromichi Niikawa,Daisuke Sakota,Ryo Kosaka,Ichiro Sakanoue,Soumei Baba,Katsuhiro Ohuchi,Tetsuhito Kigata,Carol F Farver,Kenneth R McCurry,Yoshinori Okada,Toshihiro Okamoto

Abstract

Background: Prolonged warm ischemia in uncontrolled donation after circulatory death (uDCD) potentially increases the risk of graft dysfunction in lung transplantation. To address this concern, a noninvasive, whole-body cooling approach was developed using a specialized liquid refrigerant at -21 °C. The aim of this study was to investigate whether this method reduces lung temperature and improves lung function in uDCD donors. Methods: Fifteen pigs were randomly assigned to 3 groups. In the study group (n = 5), the entire donor body was submerged in a basin containing a coolant of -21 °C, and chest compression was performed during 90 min of warm ischemia. In the sham group (n = 5), neither body cooling nor chest compression was performed during 90 min of warm ischemia. Lungs were evaluated by cellular ex vivo lung perfusion (EVLP) after 5 h of additional cold ischemia. Lungs in the donation after brain death (DBD) group (n = 5) were perfused after 1 h of cold ischemia. Results: Tracheal temperature decreased to 28.5 °C in the study group and remained at 38.1 °C in the sham group. Lungs in the study group showed higher transplant suitability with significantly higher PaO2/FiO2, and lower peak inspiratory pressure during EVLP than those in the sham group (all P < 0.05). The study group had a significantly higher ATP level, a relatively lower hypoxia-inducible factor-1α level, and lower percentage of apoptotic cells than the sham group. Conclusions: This novel cooling approach effectively reduced lung temperature during warm ischemia, resulting in improved lung function during EVLP. These data suggest that this method could mitigate ischemia-reperfusion injury in uDCD donors, expanding the donor lung pool.

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