Comparison of histidine-tryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution for organ preservation in human liver transplantation

Over a 30-month period, 60 patients (30 in each group) suffering from end-stage liver disease or primary hepatic malignancy and scheduled for liver transplantation were enrolled in a prospective, randomized study to compare two methods of liver preservation: histidinetryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution. Entry criteria for both groups were: age (18–65 years), elective surgery (transplantable or urgent category of the recipients), first transplantations and harvesting procedure performed by the same team. The parameters under investigation were the clinical and laboratory data preand post-transplantation, as well as follow-up data such as complications and survival. There were no significant differences in the two groups as far as the evaluation criteria were concerned, even when cold ischemia time was more than 15h (n=7). A slight, yet not significant, increase in late complications of the biliary anastomoses could be seen in the UW group. Hepatocellular injury (SGOT, SGPT, GLDH, lactate) appeared to be more marked in the HTK group. These results suggest that both HTK and UW solutions are appropriate for clinical use in liver transplantation, even if cold ischemia time is more than 15h.     

Comparison of HTK- and UW-solution for liver preservation tested in an orthotopic liver transplantation model in the pig

The aim of this experimental study was to compare the preservation potency of University of Wisconsin (UW) and HTK (Bretschneider) solutions in an orthotopic liver transplantation (OLT) model in pigs. Livers were harvested using an in situ perfusion technique, where organs were flushed with the solution being tested, stored on ice — cold storage (CS) — for 2 or 24 h and then transplanted. Parameters monitored were liver enzymes in serum, hepatic water content, high energy phosphates, nuclear magnetic resonance (NMR) relaxation time T2, light microscopy and bile production. CS for 24 h is an extreme in pig liver preservation and is not compatible with animal survival. Biopsies showed drastic morphological changes and grafts did not produce bile in either group. (Bile production 2 h CS: HTK, 5.6 ± 1.8 ml/h; UW, 4.7 ± 2.3 ml/h) Enzyme release after reperfusion (ASGOT, ?LDH) was higher in long-term preservation. Hepatic tissue water content significantly decreased during CS in UW preserved livers. Edema alter reperfusion (?H₂0: HTK 24 h = + 5.6%, UW 24 h= + 4.8%) and regeneration capacity after reperfusion (UW 2 h = 63%, HTK 2 h = 55%, UW 24 h = 30%, HTK 24 h = 30%) were not significantly different. However, we did not observe major differences in preservation potency between the solutions tested. Differences were correlated, rather, with length 9 time of CS, than with the solution used. Therefore, HTK solution seemed to be a low potassium containing alternative to UW solution.     

Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with UW and Euro-Collins

The aim was to evaluate the effect of HTK compared to UW and Euro-Collins (EC) on the initial graft function and long term graft survival in two prospective randomized studies. Only kidneys from heart-beating, kidney-only or kidney + heart donors were eligible for entry. Initial non-function (INF) was defined as the absence of life-sustaining renal function, requiring dialysis treatment on two or more occasions, during the first week after transplantation. To evaluate the contribution of the preservation solutions on INF in relation to other factors, a multivariate, 2-step logistic regression model was used. Randomization was performed between July 1990 and September 1992. The UW-HTK study comprised 342 donors and 611 transplants (UW: 168 donors and 297 transplants, HTK: 174 donors and 314 transplants). In the EC-HTK study 317 donors and 569 transplants were included (EC: 155 donors and 277 transplants, HTK: 162 donors and 292 transplants). INF occurred in 33 % of either HTK-(n = 105) or UW-(n = 99) preserved kidneys (P = NS), and in 29 % of the HTK-(n = 85) and in 43 % of the EC-(n = 119) preserved kidneys (P = 0.001). Multivariate analysis showed no significant influence of the preservation solution on the incidence of INF in the UW-HTK study, but factors contributing to INF were donor age, cause of death, retransplantation, and cold ischemic period. The EC-HTK study showed a significantly higher risk of INF, using EC as preservation, in addition to cold ischemic period and donor quality. The 3-year graft survival of HTK-preserved kidneys was 73 %, compared to 68 % for UW-preserved kidneys in the UW-HTK study (P = NS); while the 3-year graft survival of HTK preserved kidneys was 70 % compared to 67 % for EC-preserved kidneys in the EC-HTK study (P = NS). We can conclude that HTK is comparable to UW in its preservative abilities, using kidneys from heart-beating kidney-only donors, whereas EC as renal preservation solution should be avoided. Received: 2 November 1998 Received after revision: 10 August 1999 Accepted: 16 September 1999     

A report of the eurotransplant randomized multicenter study comparing kidney graft preservation with HTK, UW and EC solutions

Abstract Special attention has been focused in this randomized study on the primary function of renal allografts preserved with different solutions. Histidine-Tryptophane-Ketoglutarate (HTK) and University of Wisconsin (UW) solutions provided a significantly lower incidence of delayed graft function compared to Euro-Collins solution. Improved renal function after transplantation was observed in the HTK and UW groups compared to the EC group.     

UW与HTK保存液在肝脏移植术中临床效果对比的系统评价和meta分析

目的比较肝脏移植术中两种常用的器官保存液(UW液与HTK液)的临床效果。方法全面检索PubMed、Embase、Cochrane Library、中国期刊全文数据库、中国生物医学文献数据库、万方、维普等中英文数据库,纳入对比UW(UW液组)与HTK(HTK液组)两种保存液对移植肝脏保存效果的研究,提取资料并评价后用RevMan 5.3软件进行分析。结果最终纳入16篇文献共35 024例受者,meta分析结果显示,与UW液组比较,HTK液组的术后胆管并发症发生率[RR=1.30,95%CI(1.07,1.58),P=0.008]和术后7 d内天门冬氨酸氨基转移酶峰值[MD=112.45,95%CI(93.34,131.56),P<0.01]均较低,而术后移植肝原发性无功能发生率[RR=1.07,95%CI(0.52,2.18),P=0.86]、术后不同时间点移植肝和受者存活率(P>0.05)、术后再移植率[RR=0.83,95%CI(0.48,1.45),P=0.51]、急性排斥反应发生率[RR=1.27,95%CI(0.96,1.68),P=0.33]、7 d内丙氨酸氨基转移酶峰值[MD=31.79,95%CI(–161.84,225.42),P=0.75]、总胆红素水平[MD=19.42,95%CI(–10.83,49.67),P=0.21]、凝血酶原时间[MD=1.75,95%CI(0.01,3.49),P=0.838]等指标比较差异均无统计学意义。结论 HTK保存液对移植肝的保存安全且有效,具有与UW保存液相似的效果,关于二者对肝移植术后受者和移植肝远期存活率的影响仍需要大样本、高质量的随机对照试验研究来系统评价。     

Myocardial preservation with the UW solution. First European results in clinical heart transplantation

In recent years, there is a growing body of evidence that the University of Wisconsin (UW) solution offers many advantages in organ preservation with regard to preservation quality and time. We, therefore, conducted the first European prospective, randomized, clinical trial comparing myocardial performance after preservation with UW and St. Thomas Hospital (ST) solution. Preliminary results indicated superior heart function after preservation with UW solution.     

Effects of various HTK solution regimens on proteinuria after renal transplantation in dogs

Investigations were carried out by means of an autologous, heterotopic model for kidney transplantation applied to dogs. Duration of cold ischemia was 48 h. Four experimental groups were arranged. During the first 20 min following revitalization of the transplanted kidney, group 1 (HTK solution/80 cm perfusion height) showed a significant glomerular and tubular malfunction. In group 2 (HTK solution/120 cm perfusion height), only four urinary proteins with molecular weights of 25 kDa, 67 kDa, 100 kDa and >100 kDa were found. The excretion of higher molecular proteins receded over the 20-min period of observation. In both group 3 (HTK/aspartate solution) and group 4 (HTK/tryptophan solution) the quantity of excreted glomerular and tubular protein was well above that of group 2. As opposed to the Tryptophan group, a complete restoration of renal function was observed in the Aspartate group after 4 weeks. In general, the standard HTK protective solution delivered with 120 cm perfusion pressure gave the most favorable results, with the lowest levels of proteinuria and a satisfactory recovery of renal function after revitalization.     

Comparison of solutions for preservation of the rabbit liver as tested by isolated perfusion

The University of Wisconsin (UW) solution consists of a relatively complex mixture of agents. In this study we compared simpler preservation solutions, namely, histidine-tryptophan-ketoglutarate glutarate (HTK) and phosphatebuffered sucrose (PBS) with different compositions of UW solution in the isolated perfused rabbit liver model. Livers were stored cold for 24 and 48 h. After 24 h of preservation, the amount of bile produced in UW-preserved livers was significantly greater (P<0.05) than that in HTK-preserved livers. Also, there was less LDH released into the perfusate in UW-preserved livers. There was more edema and lower K+/Na+ rations in HTK-preserved livers than in UW-preserved livers (all data P<0.05). After 48 h of preservation, the differences between livers preserved in UW or HTK solution were less noticeable than at 24 h and bile production was similar. LDH and AST release were greater in HTK-preserved livers than in UW livers, but these differences were not statistically significant. Preservation in PBS for 48 h was worse than in either UW or HTK solution. Substitution of polyethylene glycol (PEG) for hydroxyethyl starch (HES) in 48-h UW-preserved livers was not effective. We conclude that solutions simpler in composition than UW solution may be effective in kidney transplantation but do not appear suitable for successuful liver preservation.     

The superiority of UW solution for maintaining ATP concentrations during pulmonary preservation

We evaluated three solutions used for preserving lungs, namely, University of Wisconsin (UW), Euro-Collins (E-C), and low potassium dextran (LPD), by measuring the high energy phosphates in the preserved lung tissue. The left lungs of Sprague-Dawley rats were excised and flushed with 5 ml of one of the solutions at 10°C through the pulmonary artery, after which they were deflated and immersed in the solution at 10°C for 24 h. The tissue adenosine triphosphate (ATP) concentration in mol/g tissue wet weight after 24 h of storage was 2.55 ± 0.48 (n = 7) in the UW lungs, 1.98 ± 0.25 (n = 6) in the E-C lungs, and 1.53 ± 0.32 (n = 4) in the LPD lungs, being significantly higher in the UW lungs than in either the E-C or LPD lungs (P < 0.05). The histopathological findings of the E-C lungs were more deteriorated, with marked interstitial edema, septal hypertrophy, and perivascular hyaline degeneration, than either the UW or LPD lungs. Thus, the findings of this study indicate the superiority of UW solution for lung preservation.     

Effect of prostaglandin E1 on preservation injury of canine liver grafts preserved in UW solution

This study investigated whether prostaglandin E₁ (PGE₁) could reduce hepatic injury to the liver graft caused by harvesting and 24-h preservation in University of Wisconsin (UW) solution in a canine model. The PGE₁-treated group was intravenously administered 0.5 g/kg per minute of PGE₁ for 30 min before harvesting, as well as a concentration of 1 mg/l PGE₁ in the washout and UW solutions. In both the PGE₁-treated and the control group, all recipients survived for 1 week or more after transplantation. Arterial ketone body ratio (AKBR) remained over 1.0 in the early postoperative period. The PGE₁ group showed significant reductions in guanase, GOT, and LDH during the early postoperative period compared to the untreated control group. Histological examination disclosed partial mitochondrial swelling, hepatocyte vacuolation, and necrosis in the control group, while such abnormalities were rarely seen in the PGE₁ group. These results suggest that PGE₁ can effectively reduce hepatic injury to liver grafts preserved in UW solution prior to transplantation.     

UW器官保存液在胰腺移植中的研究进展

近年来,糖尿病发病率在全球呈快速增长的趋势,我国患病率已达到3%.多数Ⅰ型和部分Ⅱ型糖尿病患者需要采用外源性胰岛素注射控制血糖,患者不但要承受胰岛素注射带来的痛苦,而且还不可避免地要发生远期的并发症.因此,重建内源性胰岛分泌系统是近年来人们关注的热点.大量实验表明,胰腺移植不但可以中止胰岛素依赖性糖尿病并发症的发展,还可以转归已有的并发症,明显改善患者的预后.与其他器官移植一样,移植器官的获取及保存是移植成功的前提,由于胰腺组织的特殊性,不同的器官保存液对于保存胰腺效果不一.本文将对University of Wisconsin(UW)保存液在胰腺移植中作用作一论述.     

Celsior液和UW液保存供肝的前瞻性随机对照研究

目的比较Celsior液和UW液保存供肝的效果。方法随机选取拟行肝移植的患者60例，平均分为两组，一组接受以Celsior液灌洗和冷保存的供肝（Celsior液组）移植，另一组接受以UW液灌洗和冷保存的供肝（UW液组）移植，两组在患者年龄、性别构成、肝功能分级以及原发病、肝移植术式等方面的差异无统计学意义。比较两组供肝组织学变化、术后早期肝功能恢复情况及术后3个月内缺血性胆道狭窄的发生率。结果Celsior液组供肝冷缺血时间为（8．83±1．53）h，UW液组为（9．08±1．85）h，差异无统计学意义（P〉0．05）。两组术后早期血清丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶、胆红素总量、出血时间及胆汁量的差异无统计学意义（P〉0．05），术后3个月内，Celsior液组缺血性胆道狭窄发生率为6．7％（2／30），UW液组为13．3％（4／30），差异无统计学意义（P〉0．05）。两组移植肝的组织学改变相似。结论在冷缺血时间一致的情况下，Celsior液保存供肝的效果与UW液相同。     

A preliminary report of the HTK randomized multicenter study comparing kidney graft preservation with HTK and EuroCollins solutions

The main goal of transplantation is to restore good renal function and to improve the quality of life of thousands of dialysis patients, something which can only be achieved by providing them with well functioning grafts. Delayed renal allograft function is a serious problem. It is important to prevent this complication because it makes the diagnosis of acute rejection in the early postoperative period difficult, increases the necessity for diagnostic procedures, introduces dialysis treatments and prolongs hospital stay. The aetiology of delayed graft function (DGF) is multifactorial, and factors including donor management, technique used for organ procurement and preservation, age, anatomical variations in the graft, ischemia periods, use of cyclosporine A (CyA) or recipient immunological reactions have been implicated. Using different preservation solutions DGF rates vary from 30% to 60%. Recent clinical data have demonstrated better preservation and improved renal function posttransplant with HTK and University of Wisconsin (UW) solutions compared to EuroCollins solution. In a randomized multicenter study in collaboration with the Eurotransplant organ exchange organization, the efficacy of the HTK solution in renal transplantation was compared to EuroCollins and UW solutions in two parallel prospective randomized trials. The first preliminary results comparing HTK and EuroCollins solutions are reported here.     

HX—3液和UW液保存大鼠肝脏效果的比较

采用大鼠肝脏非循环离体灌注模型比较自制的ＨＸ－３液和ＵＷ液对大鼠肝脏的保存效果。实验结果显示，经ＨＸ－３液原位灌洗并保存４８小时的肝脏肝组织含水量正常，而同等条件下换用ＵＷ液，肝组织的含水量虽无明显变化，但都低于正常值；随着保存时间的延长，两组肝窦内皮细胞死亡率逐渐上升，但在２４小时以内两组肝窥内皮细胞死亡率的差异不显著．     

自制肝脏保存液在大鼠原位肝移植模型中的应用

目的研制一种新型的专用于肝脏保存的溶液,以期达到价廉、专用、损伤小并能长时间保存的目标。方法自制肝脏保存液;建立大鼠原位肝移植模型;使用自制肝脏保存液(A组)、UW液(B组)和HC-A液(C组)保存大鼠肝脏2、8、24h后行大鼠原位肝移植,于移植后6 h比较各项肝脏功能。结果对于ALT、AST、HA,自制肝脏保存液组及其亚组与UW液组同步升高(P>0.05),与HC-A液组比较,前者的含量均低,差异有统计学意义(P<0.05)。对于LDH、STB,自制肝脏保存液组及其亚组与HC-A液组同步升高(P>0.05),与UW液组比较,前者的含量均高(P<0.05)。结论经大鼠原位肝移植模型证实,自制肝脏保存液与UW液在保护肝脏功能方面作用相当,优于HC-A液。     

Protective effects of the lazaroid U74500A and lidoflazine on liver preservation with UW solution

The effect of adding a 21-aminosteroid, U74500A, and a Ca²⁺ antagonist, lidoflazine, alone and together to UW solution was assessed in a rat liver preservation model. Following preservation, the livers were reperfused using a closed circuit, and the release of hepatocellular enzymes (ASAT, ALAT, and LDH) into the perfusate was determined with increasing time. Both drugs reduced the amount of enzymes lost from the liver. The combination of the two drugs was better than either drug alone. These data suggest that both agents may be of value in organ preservation for clinical liver transplantation.