Kahn Judith, Schemmer Peter
Division of Transplant Surgery, Department of Surgery, Medical University of Graz, Graz, Austria.
Transplant Center Graz, Medical University of Graz, Graz, Austria.
Curr Pharm Biotechnol. 2017;18(15):1237-1248. doi: 10.2174/1389201019666180409165154.
The later fate of a graft is highly dependent on its initial quality. Aside from that the three predominant phases during transplantation (Tx) organ retrieval, cold static preservation and reperfusion cause in a direct and indirect manner graft injury. There is complex ischemia reperfusion injury (IRI) triggered during the whole process of Tx which contributes to further damage of the graft.
The today's organ preservation with commercially available solutions that all have toxic potential per se is still imperfect. Thus, improved preservation solutions are desperately needed to be able to even safely preserve grafts from extended criteria donors which are more susceptible to especially IRI. Most recently, a modified less toxic histidine-tryptophan-ketoglutarate (HTK; Custodiol®) the so called histidine-tryptophan-ketoglutarate-N (HTK-N) for both better cardioplegia and organ preservation for Tx has been developed. It is characterized as an electrolyte balanced, iron chelatorsupplemented, and amino acid-fortified organ preservation solution with replaced buffer ameliorating resistance to injury during the cold static preservation with subsequent IRI. Numerous in vitro and in vivo experiments have shown the superiority of the HTK-N solution in ROS generation, microcirculation, and subsequent inflammatory response compared with HTK.
According to data available to date, HTK-N has both lower cytotoxicity and higher protective potential than HTK. First clinical studies on both HTK-N for cardioplegia in cardiac surgery and for organ preservation for transplantation have been performed or are ongoing.
In this review, the novelty and composition of HTK-N and studies investigating the potential of this new solution are focussed, after summarizing the most relevant molecular mechanisms of IRI.
移植物的后期命运高度依赖于其初始质量。除此之外，移植过程中的三个主要阶段（器官获取、冷静态保存和再灌注）会直接或间接导致移植物损伤。在整个移植过程中会引发复杂的缺血再灌注损伤（IRI），这会进一步损害移植物。
目前使用的市售保存液本身都具有潜在毒性，器官保存仍不完善。因此，迫切需要改进保存液，以便能够安全地保存来自扩大标准供体的移植物，这些供体对IRI尤其敏感。最近，一种改良的、毒性较小的组氨酸 - 色氨酸 - 酮戊二酸（HTK；Custodiol®），即所谓的组氨酸 - 色氨酸 - 酮戊二酸 - N（HTK - N）已被开发出来，用于更好的心脏停搏和移植器官保存。它的特点是一种电解质平衡、补充铁螯合剂且强化氨基酸的器官保存液，其替代缓冲剂可改善冷静态保存及随后IRI期间的抗损伤能力。大量的体外和体内实验表明，与HTK相比，HTK - N溶液在活性氧生成、微循环和随后的炎症反应方面具有优势。
根据目前可得的数据，HTK - N的细胞毒性低于HTK，保护潜力更高。关于HTK - N在心脏手术中用于心脏停搏以及在移植中用于器官保存的首批临床研究已经完成或正在进行中。
在本综述中，在总结IRI最相关的分子机制后，重点关注了HTK - N的新颖性、组成以及研究这种新溶液潜力的研究。
