Department of Surgery, UMCG, University of Groningen, Groningen, the Netherlands.
Department of Pathology and Medical Biology, UMCG, University of Groningen, Groningen, the Netherlands.
PLoS One. 2019 Nov 19;14(11):e0225152. doi: 10.1371/journal.pone.0225152. eCollection 2019.
Since the start of organ transplantation, hypothermia-forced hypometabolism has been the cornerstone in organ preservation. Cold preservation showed to protect against ischemia, although post-transplant injury still occurs and further improvement in preservation techniques is needed. We hypothesize that hydrogen sulphide can be used as such a new preservation method, by inducing a reversible hypometabolic state in human sized kidneys during normothermic machine perfusion.
Porcine kidneys were connected to an ex-vivo isolated, oxygen supplemented, normothermic blood perfusion set-up. Experimental kidneys (n = 5) received a 85mg NaHS infusion of 100 ppm and were compared to controls (n = 5). As a reflection of the cellular metabolism, oxygen consumption, mitochondrial activity and tissue ATP levels were measured. Kidney function was assessed by creatinine clearance and fractional excretion of sodium. To rule out potential structural and functional deterioration, kidneys were studied for biochemical markers and histology.
Hydrogen sulphide strongly decreased oxygen consumption by 61%, which was associated with a marked decrease in mitochondrial activity/function, without directly affecting ATP levels. Renal biological markers, renal function and histology did not change after hydrogen sulphide treatment.
In conclusion, we showed that hydrogen sulphide can induce a controllable hypometabolic state in a human sized organ, without damaging the organ itself and could thereby be a promising therapeutic alternative for cold preservation under normothermic conditions in renal transplantation.
自器官移植开始以来，低温诱导的低代谢一直是器官保存的基石。冷保存显示可以预防缺血，尽管仍然会发生移植后损伤，需要进一步改进保存技术。我们假设硫化氢可以作为一种新的保存方法，通过在常温机器灌注期间诱导人大小肾脏的可逆低代谢状态。
将猪肾连接到离体、氧补充、常温血液灌注装置上。实验组（n = 5）接受 85mg NaHS 100ppm 的输注，并与对照组（n = 5）进行比较。作为细胞代谢的反映，测量耗氧量、线粒体活性和组织 ATP 水平。通过肌酐清除率和钠的分数排泄来评估肾功能。为了排除潜在的结构和功能恶化，研究了肾脏的生化标志物和组织学。
硫化氢强烈降低了 61%的耗氧量，这与线粒体活性/功能的显著下降有关，而不会直接影响 ATP 水平。硫化氢处理后，肾生物标志物、肾功能和组织学没有改变。
总之，我们表明硫化氢可以在人大小的器官中诱导可控的低代谢状态，而不会损害器官本身，因此可能是肾移植常温下冷保存的一种有前途的治疗替代方法。
