研究背景：最近关于医学气体，包括一氧化碳和氢气证明有很好的治疗作用，本研究主要是评价单独呼吸一氧化碳、氢气和联合呼吸两种气体对心脏冷缺血再灌注损伤的作用。冷缺血再灌注损伤是关于器官移植方面最重要的研究课题，其实质和目的是研究器官体外保护。

研究方法是采用同种异体心脏移植，心脏进行6或18小时的体外处理。通过观察存活率、形态学、细胞凋亡、有关标志基因表达等指标。以判断单独呼吸一氧化碳、氢气和联合呼吸两种气体对心脏冷缺血再灌注损伤的治疗作用。

结果：6小时冷缺血再灌注后，呼吸2%的氢气或250 ppm一氧化碳能降低心脏损伤。18小时冷缺血再灌注可造成更严重的心脏损伤，单独呼吸氢气或一氧化碳均不能有效保护。联合呼吸2%的氢气和250 ppm一氧化碳能显著改善心脏损伤，可降低心脏梗死体积、血清troponin I和CPK水平。单独呼吸氢气可明显降低MDA和box-1水平。一氧化碳能部分保护氧化损伤，但可显著降低炎症因子的mRNA的表达水平和细胞凋亡。结论：两种气体能从不同角度发挥作用，联合使用能取得更好的效果。

        一氧化碳和氢都可以保护器官损伤，本研究主要是研究联合应用是否可以获得更好的效果，采用形态学、酶学等常规技术方法，研究证明确实能达到协同治疗效果。该研究是氢分子医学的最新文章，是来自美国Pittsburgh大学器官移植中心，过去他们曾经在小肠移植和肾脏移植方面发表了文章。现在的研究属于心脏移植。按照常规的思路，估计他们也有关于肝脏移植的研究。

       Nakao教授最近与我进行了很多关于氢的生物学效应方面的探讨，并把我介绍给许多日本这个领域的教授，给我的帮助非常大，感觉他是一个非常优秀的学者。他目前发表论文已经有100多篇，有许多高质量的文章，过去他的兴趣主要是一氧化碳，现在开始对氢气的效应十分关注，美国现在共发表6篇论文，其中他发表了3篇，其中2篇5分以上，质量是最好的，作为一个40岁左右的临床医生，能有这些成就非常不容易。

ABSTRACT

Background: Recent advances in novel medical gases, including hydrogen and carbon monoxide (CO), have demonstrated significant opportunities for therapeutic use. This study was designed to evaluate the effects of inhaled hydrogen, CO, or both on cold ischemia/reperfusion (I/R) injury of the myocardium.

Methods: Syngeneic heterotopic heart transplantation was performed in rats after 6 or 18 hours of cold ischemia in Celsior. Survival, morphology, apoptosis, and marker gene expression were assessed in the grafts after in vivo inhalation of hydrogen (1-3%), CO (50- 250 ppm), both, or neither. Both donors and recipients were treated for 1 hour before and 1 hour after reperfusion.

Results: After 6 hours cold ischemia, inhalation of hydrogen (>2%) or CO (250 ppm) alone attenuated myocardial injury. Prolonged cold ischemia for 18 hours resulted in severe myocardial injury, and treatment with hydrogen or CO alone failed to demonstrate significant protection. Dual treatment with hydrogen and CO significantly attenuated I/R graft injury, reducing the infarcted area and decreasing in serum troponin I and CPK. Hydrogen treatment alone significantly reduced malondialdehyde levels and serum high-mobility group box-1 protein levels as compared with air-treated controls. In contrast, CO only marginally prevented lipid peroxidation, but suppressed I/R-induced mRNA upregulation for several proinflammatory mediators and reduced graft apoptosis.

Conclusions: Combined therapy with hydrogen and CO demonstrated enhanced therapeutic efficacy via both antioxidant and anti-inflammatory mechanisms, and may be potentially a clinically feasible approach for preventing cold I/R injury of the myocardium.