一种可保护移植心脏的氢气水浴新方法

最近美国Pittsburgh大学心脏外科和器官移植中心，在The Journal of Heart and Lung Transplantation发表一篇关于氢气水浴保护体外心脏器官的方法，该方法给这一领域提出了一种切实可行的技术，可以推进氢气在临床，特别是在器官移植领域的应用。这种方法曾经被日本一家从事氢气水生产的公司推广作为临床注射氢气溶液的技术，现在该技术被用于体外器官移植，非常值得推荐。主要原因是这种技术不存在太多的伦理限制，只是将传统的器官保护袋放在溶解氢气的溶液中，依靠氢气强大的扩散能力，在不影响器官保护袋内任何成分的前提下，氢气可以穿透保护袋材料进入保护袋内，然后扩散到保护的器官内。要知道，过去许多研究中氢气的有效浓度只在微摩尔级，而体外保存液的氢气浓度可以达到毫摩尔级，这在给药浓度具有极大的优势。

背景：外源性氢气主要通过抗氧化抗炎症抗细胞凋亡等机制发挥细胞保护效应， 在许多疾病模型中，保护器官移植都已经证明存在上述效应。本研究的目的是评价采用新的氢气水保存装置对体外心脏的保护效果。

研究方法，建立大鼠异位器官移植模型，首先将同源心脏从60-70周龄Lewis大鼠或异源心脏从成年12周龄Brown Norway大鼠体内取出，放入冷保存液。移植心脏放入Celsior液塑料袋内，浸入经电解饱和氢气的冷水中，以使氢气扩散到冷保存液内。然后心脏被异位移植到Lewis大鼠。

结果：在移植后3小时，两种实验对照组都发现血清肌钙蛋白I和肌酸磷酸激酶含量显著升高，并表现出持续的炎症反应，如中性粒细胞浸润和促炎症因子和趋化因子mRNA表达明显上调。而经过氢气水处理的心脏心脏损伤和炎症反应均明显改善。而且氢气水沐浴的心脏其线粒体受损明显缓解，ATP水平明显增加。研究结果表明，采用这种新的装置确实可以将氢气输送到器官保存液体中的心脏组织内，而且可以发挥对冷缺血再灌注损伤的保护作用。可以作为器官移植保存的手段这种新的设备值得尝试。

A novel method of preserving cardiac grafts using a

hydrogen-rich water bath

BACKGROUND

Exogenously administered hydrogen exerts cytoprotective effects through anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms in various disease settings, including organ transplantation. Our objective in this study was to evaluate the efficacy of a novel cold storage device equipped with a hydrogen-rich water bath.

METHODS

The study used an established rat heterotopic transplantation model. Syngeneic heart grafts from elderly donors (60- to 70-week-old Lewis rats) or allografts from adult donors (12-week-old Brown Norway rats) were exposed to prolonged cold preservation. The cardiac grafts were stored in plastic bags containing Celsior, which were immersed in the cold water bath equipped with an electrolyzer to saturate the water with hydrogen. The cardiac grafts then were heterotopically engrafted into Lewis rat recipients.

RESULTS

In both experimental settings, serum troponin I and creatine phosphokinase were markedly elevated 3 hours after reperfusion in the control grafts without hydrogen treatment. The grafts exhibited prominent inflammatory responses, including neutrophil infiltration and the upregulation of messenger RNAs for pro-inflammatory cytokines and chemokines. Myocardial injury and inflammatory events were significantly attenuated by organ storage in the hydrogen-rich water bath. The grafts stored using the hydrogen-rich water bath also exhibited less mitochondrial damage and a higher adenosine triphosphate content.

CONCLUSIONS

Hydrogen delivery to cardiac grafts during cold preservation using a novel hydrogen-supplemented water bath efficiently ameliorated myocardial injury due to cold ischemia and reperfusion. This new device to saturate organs with hydrogen during cold storage merits further investigation for possible therapeutic and preventative use during transplantation.