Corps C L, Shires M, Crellin D, Smolenski R, Pratt J, Potts D, Lodge J P A
Department of Hepatobiliary and Transplant Surgery, St. James's University Teaching Hospital, Leeds, West Yorkshire, England.
Transplant Proc. 2009 Nov;41(9):3567-70. doi: 10.1016/j.transproceed.2009.04.009.
Several articles have compared histidine-tryptophan-ketoglutarate solution (HTK) with other preservation solutions in both liver and kidney transplantation, and the results suggest that HTK is as good or better than the criterion standard University of Wisconsin solution (UW) for short periods of cold ischemia, such as in live donation, but that it is not so efficient for longer periods of cold ischemia, causing a higher incidence of delayed graft function.
To evaluate energy levels, metabolites, and histologic findings to determine why HTK is inefficient for longer periods of cold ischemia.
Rat livers were perfused with either HTK or UW, and at various times, tissue samples were obtained for analysis of adenine triphosphate and metabolites using high-performance liquid chromatography or for histologic analysis.
The high energy charge observed with HTK-perfused livers plateaued after 5 minutes, and by 60 minutes began to decrease, following the same trend as other samples. The plateau is due to excess available glucose; however, after 1 hour, it is beginning to be consumed. Low levels of uridine, required for glycogen synthesis, are found in HTK-perfused livers, which suggests that at reperfusion, there is none available, whereas the higher concentrations found in UW-perfused livers may be advantageous after reperfusion. This will be especially detrimental to use of HTK because glycogen is used up rapidly because of the presence of alpha-ketoglutarate in the solution, enabling continuation of the tricarboxylic acid cycle.
Overall, HTK seems to do well for the first 2 hours, after which any advantage observed initially starts to disappear. A liver perfused in HTK and transplanted after more than 1 hour reacts like an organ from an individual who has been starved, because of the low energy charge and absence of a glycogen store or ability to synthesis glycogen because of lack of uridine. Livers perfused with UW demonstrate higher levels of uridine and do not lose their glycogen content to the same extent as HTK-perfused livers. These findings explain in part why HTK sometimes causes delayed graft function after longer periods of cold ischemia.
多篇文章在肝移植和肾移植中对比了组氨酸 - 色氨酸 - 酮戊二酸溶液（HTK）与其他保存溶液，结果表明，在短时间冷缺血（如活体捐赠）中，HTK与标准的威斯康星大学溶液（UW）效果相当或更佳，但在长时间冷缺血时效率不高，导致移植肝功能延迟的发生率更高。
评估能量水平、代谢物和组织学结果，以确定HTK在长时间冷缺血时效率低下的原因。
用HTK或UW灌注大鼠肝脏，在不同时间获取组织样本，使用高效液相色谱法分析三磷酸腺苷和代谢物，或进行组织学分析。
用HTK灌注的肝脏观察到的高能量电荷在5分钟后趋于平稳，到60分钟时开始下降，与其他样本趋势相同。这种平稳是由于葡萄糖供应过剩；然而，1小时后，葡萄糖开始被消耗。在HTK灌注的肝脏中发现糖原合成所需的尿苷水平较低，这表明在再灌注时没有可用的尿苷，而在UW灌注的肝脏中发现的较高浓度的尿苷在再灌注后可能是有利的。这对HTK的使用尤其不利，因为溶液中存在α - 酮戊二酸，糖原会迅速耗尽，从而使三羧酸循环得以继续。
总体而言，HTK在前2小时似乎效果良好，之后最初观察到的任何优势开始消失。用HTK灌注并在1小时以上后移植的肝脏，其反应类似于饥饿个体的器官，因为能量电荷低，且由于缺乏尿苷而没有糖原储备或合成糖原的能力。用UW灌注的肝脏显示出较高水平的尿苷，并且糖原含量不会像用HTK灌注的肝脏那样大幅减少。这些发现部分解释了为什么HTK在长时间冷缺血后有时会导致移植肝功能延迟。
