Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs

Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs
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DOI:
10.1371/journal.pone.0222863
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发表时间:
2019-10-01
期刊:
影响因子:
3.7
通讯作者:
Sano, Motoaki
Sano, Motoaki
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kobayashi, Eiji;Sano, Motoaki

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已经设计了各种方法来将氢气溶解在器官保存溶液中,包括使用氢气瓶、电解或氢生成剂。然而,这些方法需要相当多的时间和精力来准备。我们研究了一种实用的技术,快速溶解氢气的器官保存液中使用的贮氢合金罐。通过这种方法产生的含氢器官保存溶液的功效在来自循环停止的供体的肾移植的小型猪模型中进行了测试。氢气溶解所需的时间仅为2-3分钟。当在0.06MPa的压力下将氢气注入到含有冷ETK器官保存溶液的袋中并且随后将袋打开到空气中时,溶解的氢浓度保持在1.0mg/L或更高达4小时。在停循环30 min造成热缺血损伤后,切取供肾,用含氢冷ETK液或无氢冷ETK液灌注5 min。含氢冷ETK溶液的灌注速率从初始阶段开始比无氢ETK溶液快。在移植前将肾脏在无氢保存液中储存1小时后,在术后第6天处死时,未观察到尿液产生,并且在移植的肾脏中未检测到血流。相反,在含氢保存液中保存1或4小时后,在膀胱中检测到尿液,并且在移植肾中确认了血流。这种将氢气溶解在器官保存溶液中的方法是一种实用的技术,可以将受损的器官转化为可移植的器官,这些器官可以安全地用于任何从捐赠者身上取出器官的临床环境。
Various methods have been devised to dissolve hydrogen gas in organ preservation solutions, including use of a hydrogen gas cylinder, electrolysis, or a hydrogen-generating agent. However, these methods require considerable time and effort for preparation. We investigated a practical technique for rapidly dissolving hydrogen gas in organ preservation solutions by using a canister containing hydrogen-absorbing alloy. The efficacy of hydrogen-containing organ preservation solution created by this method was tested in a miniature pig model of kidney transplantation from donors with circulatory arrest. The time required for dissolution of hydrogen gas was only 2-3 minutes. When hydrogen gas was infused into a bag containing cold ETK organ preservation solution at a pressure of 0.06 MPa and the bag was subsequently opened to the air, the dissolved hydrogen concentration remained at 1.0 mg/L or more for 4 hours. After warm ischemic injury was induced by circulatory arrest for 30 minutes, donor kidneys were harvested and perfused for 5 minutes with hydrogen-containing cold ETK solution or hydrogen-free cold ETK solution. The perfusion rate was faster from the initial stage with hydrogen-containing cold ETK solution than with hydrogen-free ETK solution. After storage of the kidney in hydrogen-free preservation solution for 1 hour before transplantation, no urine production was observed and blood flow was not detected in the transplanted kidney at sacrifice on postoperative day 6. In contrast, after storage in hydrogen-containing preservation solution for either 1 or 4 hours, urine was detected in the bladder and blood flow was confirmed in the transplanted kidney. This method of dissolving hydrogen gas in organ preservation solution is a practical technique for potentially converting damaged organs to transplantable organs that can be used safely in any clinical setting where organs are removed from donors.