Department of General, Visceral and Transplant Surgery, University Hospital Muenster, 48149 Muenster, Germany.
Int J Mol Sci. 2020 Sep 4;21(18):6468. doi: 10.3390/ijms21186468.
To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.
为了改善缺血引起的移植物损伤,优化器官保存仍然是实体器官移植的一个关键标志事件。尽管有许多保存液在使用,但它们仍然存在功能上的局限性。在这里,我们简要回顾了一种改良的组氨酸-色氨酸-酮戊二酸(HTK)溶液,称为 HTK-N。它的组成与标准 HTK 溶液不同,具有更大的抗氧化能力,并提供内在的毒性以及改善对冷的耐受性,以减轻器官移植中的冷保存损伤。氨基酸甘氨酸、丙氨酸和精氨酸被补充,N-乙酰组氨酸部分取代组氨酸,天冬氨酸和乳酰酸盐取代氯化物。几项体外研究证实了 HTK-N 优于 HTK,在动物模型中进行了肝、肾、胰腺、小肠、心脏和肺移植的体内试验,以调整所需条件下的成分,以及确定其无害性、适用性和潜在优势。HTK-N 溶液已被证明在体内和体外保存肝和心脏移植物方面具有优势。因此,不可避免的是需要进行正在进行的临床试验和在大型动物模型中的进一步研究,以及随后在人类中的研究,以显示其在器官移植后继发缺血引起的移植物损伤最小化方面的能力。