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.     

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.     

Effect of glycine on isolated,perfused rabbit livers following 48-hour preservation in University of Wisconsin solution without glutathione

Glycine has been shown to decrease membrane injury in isolated cells due to hypoxia or cold ischemia. The mechanisms of action of glycine are not known, but glycine may be useful in organ preservation solutions or in treating recipients of liver transplantation. In this study the isolated, perfused rabbit liver was used to measure how glycine affected liver performance after 48-h preservation in University of Wisconsin (UW) solution without added glutathione. UW solution is less effective for 48-h liver preservation when glutathione is omitted. Rabbit livers stored for 48 h without glutathione show a large increase in enzyme release (LDH and AST) from the liver and a reduction in bile production. The addition of 15 mM glycine to UW solution, in place of glutathione, did not improve bile production or reduce enzyme release. However, infusion of 10 mM glycine into the reperfused liver lowered LDH release significantly (from 2383±562 units/100 g to 1426±286 units/100 g) during the initial reperfusion of the 48-h preserved liver. Hepatamine, a parenteral nutrition solution containing glycine, as well as other amino acids, was also effective in lowering LDH release from the preserved liver. Although glycine reduced LDH release, it did not decrease the amount of AST released from the liver, nor did it improve bile production. Thus, we conclude that glycine, either in UW solution or given to the liver upon reperfusion, has no significantly beneficial effect as tested in this model. Further testing of glycine, however, should be conducted in an orthotopic transplant model in the rat or dog.     

Evaluation of a Modified HTK Solution Containing the New Iron Chelator LK 614 in an Isolated Rat Liver Perfusion Model

Background: Cold storage-induced injury to donor organs remains a persistent problem in transplantation medicine. We here evaluated a modified HTK solution including, among others, a new, membrane-permeable iron chelator, LK 614, in the isolated perfused rat liver model. Methods: Rat livers were stored at 4°C for 24 hr in modified HTK solution, in modified HTK solution with LK 614 or in traditional HTK solution, and reperfused for 60 min at 37°C with Krebs-Henseleit buffer (KH buffer). Bile secretion and lactate dehydrogenase (LDH) release into the perfusate were measured, and hepatic microcirculation evaluated optically after the addition of trypan blue to the perfusate. Biopsies were evaluated by a pathologist blinded to the experimental conditions. Results: Compared with HTK-preserved livers, LDH leakage was significantly lower and bile secretion significantly higher in the modified HTK solution with the iron chelator (both p <. 05), while values for the modified solution without the iron chelator were in between (no significant difference to either of the two other solutions). The hepatic microcirculation was also preserved best in livers stored in the modified HTK solution with LK 614. Histomorphological investigation confirmed the improved preservation in the modified HTK solution with LK 614. Conclusions: These results suggest that livers might be better preserved in modified HTK solution containing the iron chelator LK 614 (and also, but less so, in the modified solution without the iron chelator) than in the original HTK solution, and such a modified solution should now be evaluated in an animal model of liver transplantation.     

The impact of liver preservation in HTK and UW solution on microcirculation after liver transplantation

Severe microcirculatory disturbances due to endothelial cell damage and leukocyte adherence during reperfusion of transplanted livers are considered to contribute to early graft failure. Since the degree of reperfusion injury after liver transplantation depends on the length of preservation time and the solution used for preservation, the aim of our study was to assess three solutions with respect to microvascular perfusion and leukocyte adhesion. Therefore, rat livers were stored up to 24 h in Euro-Collins (EC), University of Wisconsin (UW), or histidin-tryphtophan-ketoglutarate (HTK) solutions prior to orthotopic transplantation. The livers were studied in situ 60 min postoperatively using intravital fluorescence video microscopy. Using simple syringe flushing (10 ml), sinusoidal perfusion decreased below 50% in EC preserved livers after 8 h preservation, in HTK preserved livers after 16 h preservation, and remained higher than 70% in livers preserved in UW up to 24 h. Permanent adhesion of leukocytes was increased more rapidly in organs after 1, 8, 16, and 24 h preservation in HTK (16%, 15%, 34%, and 49.7% ± 4.7%) compared to those preserved in UW (15%, 18%, 17%; and 32.7% ± 3.3%; P < 0.05). Using a 10-fold volumn of the organ weight of HTK solution during the harvesting procedure, with an 8 min equilibration period, sinusoidal perfusion (39.6 ± 4.7%) and leukocyte adhesion (42.7 ± 3.1%) were not improved after 24 h. In contrast, equilibration with a volumn of approximately 40-times the liver weight improved sinusoidal perfusion (70.8% ± 2.7%; P < 0.01) and leukocyte adhesion (24.9% ± 3.1%; P < 0.01) significantly. Thus, using HTK solution, simple flushing prior to long-term cold storage resulted in microcirculatory disturbances when compared to UW solution. Larger volumns of HTK solution with an additional equilibration period of 8 min, however, reduced leukocyte adhesion and improved sinusoidal perfusion to a similar degree as UW solution.     

Comparison of University of Wisconsin (UW) and Eurocollins (EC) preservation solutions in a rat liver transplant model

The Eurocollins (EC) and University of Wisconsin (UW) preservation solutions were compared in a rat liver transplant model. After hepatectomy, 48 rat livers were flushed with either EC or UW preservation solution and were randomly assigned to 1, 12, 24, and 30 h of preservation at 4°C, resulting in eight groups each containing six livers. Following preservation, orthotopic liver transplantation with reconstruction of the hepatic artery was performed. The efficacy of the preservation solution was assessed at 48 h post-transplantation by survival histological features and aspartate transaminase assay (AST) values. None of the rats survived 30 h of liver preservation with EC whereas five out of six rats did with UW preservation. After 24 h of liver preservation, three of the six rats in the EC group survived, compared to all six rats in the UW group. Histological evidence of severe ischemia was found in both groups in all but one survivor (UW, 24 h). After 12 h of EC preservation, one rat died within 48 h and severe ischemic changes were found in the remaining five rats. Among the rats with 12 h of UW preservation, only two out of six showed ischemic changes, and all six rats survived beyond 48 h. Without preservation (1 h), ischemic damage was found in two out of six rats in each group and all rats survived. The median AST values were higher in the EC groups than in the UW groups; the difference became significant after 12-h preservation (EC 900 IU/l versus UW 465 IU/l) and 24-h preservation (EC 5220 IU/l versus UW 631 IU/l). However, the median AST value in the five surviving rats whose livers had been preserved for 30 h in UW climbed to 1880 (950–2240) IU/l.. We conclude that UW solution provides better long-term preservation than EC solution. However, even with UW solution, the observed mortality, the severity of ischemic changes, and the pronounced increase in the median AST value cast doubt upon the safety of liver preservation beyond 24 h.     

SX-1液对肝脏保存效果的实验研究

目的 应用改良后的Kamada二袖套法大鼠原位肝移植模型,检验SX-1液、HC-A液和UW液对肝脏保存的效果.方法 在无菌条件下配制肝脏保存液.建立大鼠原位肝移植模型.使用SX-1液、UW液和HC-A液保存大鼠肝脏2、8、24 h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,SX-1液组(2、8、24 h)与UW液组同步升高,分析无统计学意义(P＞0.05),与HC-A液组相比,差异有统计学意义(P＜0.05).对于LDH,SX-1液组(2 h、8 h、24 h)与HC-A液组同步升高,差异无统计学意义(P＞0.05),与UW液组相比,差异有统计学意义(P＜0.05).对于分泌胆汁的肝脏个数,各组别与分泌胆汁的肝脏个数无差别(P＞0.05).本组内各时间点分泌胆汁个数有差别(P＜0.05).随肝脏保存时间增长,分泌胆汁的肝脏个数减少.结论 经大鼠原位肝移植模型证实,SX-1液在肝脏酶学方面与UW液作用相当,超过HC-A液水平.肝移植后6 h肝脏分泌胆汁的个数方面,SX-1液与HC-A液、UW液间无明显差别.     

In vitro evaluation of donor liver preservation fluids on human hepatocyte function

Successful liver transplantation depends on adequate preservation of cellular function. We therefore tested the effects of two currently used liver preservation fluids, Euro-Collins (EC) solution and University of Wisconsin (UW) solution, on the viability and some functional activities of hepatocytes isolated from human livers. Cells in primary culture were maintained under hypoxic (95% N₂/5% CO₂) and hypothermic (4°C) conditions for 24 h, either in EC or UW solution. This treatment did not result in significant hepatocyte damage, as judged by phase contrast microscopy, intracellular LDH release, and the MTT mitochondrial test. However, neutral red uptake indicated that lysosomal functions were slightly affected (35% decrease) when compared to control conditions. At the end of the hypoxia/hypothermia period, hepatocyte monolayers were incubated at 37°C under normoxic conditions for 24 h, in order to simulate the reperfusion of a transplanted liver. Three drugs-midazolam, diazepam, zidovudine-were used as diagnostic substrates to check the metabolic abilities of human hepatocytes replaced in normal conditions. Both phase I (hydroxylation, demethylation) and phase II (glucuronidation) metabolic reactions were affected by the hypoxia/hypothermia shock. Indeed, a 30%–50% decrease in these activities was observed as compared to values obtained in control hepatocytes. No difference could, however, be found at the cellular level regarding the solution used for cold storage. These results suggest that the superiority of UW over EC solution, already reported in clinical practice after transplantation of preserved human livers, was not due to a better preservation of the hepatocytes.     

Comparison of Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Preservation in Renal Transplantation

Histidine-tryptophan-ketoglutarate (HTK) is replacing University of Wisconsin (UW) solution as the preservation fluid for renal allografts in many centers, but recent large-scale data to support this transition are lacking. We conducted a retrospective analysis of patient and graft outcomes after renal transplantation at our center, comparing 475 consecutive living donor and 317 deceased donor transplants since the adoption of HTK with equal numbers of grafts preserved using UW solution. Data collected included donor and recipient age, race, sex, comorbidities and graft ischemia time. Graft and patient survival, as well as the incidence of delayed graft function (DGF), were studied by Kaplan–Meier and Cox regression analysis. No significant difference was seen in either patient or graft survival. Deceased donor kidneys in the HTK group had a higher incidence of DGF than the UW cohort, whereas this trend was reversed in the case of living donor organs. In multivariate analysis, HTK was associated with a significant risk reduction on the incidence of DGF. Prolonged preservation with HTK compared to UW was not associated with excess risk to the graft or patient. In summary, HTK demonstrated efficacy similar to UW in terms of patient and graft survival.     

High-Na + low-K + UW cold storage solution reduces reperfusion injuries of the rat liver graft

The isolated perfused rat liver model was used to assess graft viability after 24 h of cold preservation. Two solutions were compared for liver preservation: Belzer's original UW solution (high-K ⁺ UW) and a solution containing the same components but with inverted concentrations of sodium and potassium (high-Na ⁺ UW). During the 120 min of normothermic reperfusion, livers preserved in the high-Na ⁺ UW solution released lower levels of creatine kinase-BB isoenzyme, transaminases (ALT and AST), and potassium than those preserved in the high-K ⁺ UW solution. Bile flow and biliary excretion of indocyanine green increased when livers were preserved in the high-Na ⁺ UW solution. We found no statistical differences for oxygen consumption and tissue ATP concentration. The results of this study support the concept that a high-Na ⁺ UW solution is a more effective means of preserving rat livers, at least after 24 h of cold-storage and 120 min of reperfusion in the isolated perfused model, than the original high-K ⁺ UW solution. Liver preservation in the high-Na ⁺ UW solution reduces damage to sinusoidal endothelial and hepatocellular cells. The use of an extracellular-like Belzer cold storage solution eliminates potassium-related problems in cold preservation and subsequent normothermic reperfusion while keeping all the qualities of the original UW solution. Received: 26 August 1997 Received after revision: 12 November 1997 Accepted: 28 November 1997     

Histidine-Tryptophan-Ketoglutarate (HTK) Is Associated with Reduced Graft Survival of Deceased Donor Kidney Transplants

Single-center studies have reported equivalent outcomes of kidney allografts recovered with histidine-tryptophan-ketoglutarate (HTK) or University of Wisconsin (UW) solution. However, these studies were likely underpowered and often unadjusted, and multicenter studies have suggested HTK preservation might increase delayed graft function (DGF) and reduce graft survival of renal allografts. To further inform clinical practice, we analyzed the United Network for Organ Sharing (UNOS) database of deceased donor kidney transplants performed from July 2004 to February 2008 to determine if HTK (n = 5728) versus UW (n = 15 898) preservation impacted DGF or death-censored graft survival. On adjusted analyses, HTK preservation had no effect on DGF (odds ratio [OR] 0.99, p = 0.7) but was associated with an increased risk of death-censored graft loss (hazard ratio [HR] 1.20, p = 0.008). The detrimental effect of HTK was a relatively late one, with a strong association between HTK and subsequent graft loss in those surviving beyond 12 months (HR 1.43, p = 0.007). Interestingly, a much stronger effect was seen in African-American recipients (HR 1.55, p = 0.024) than in Caucasian recipients (HR 1.18, p = 0.5). Given recent studies that also demonstrate that HTK preservation reduces liver and pancreas allograft survival, we suggest that the use of HTK for abdominal organ recovery should be reconsidered.     

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     

Microcirculatory disturbances and leucocyte adherence in transplanted livers after cold storage in Euro-Collins,UW and HTK solutions

Integrity of the hepatic microcirculation and maintenance of endothelial cell viability are critical components in preventing primary non-function after liver transplantation. Therefore, hepatic microcirculation and leucocyte-endothelial interaction were studied in rat livers stored for 1 h in Euro-Collins (EC), University of Wisconsin (UW), and histidine-tryptophan-ketoglutarate (HTK) solutions and subsequently transplanted. One hour after transplantation surgery, the livers were exposed under an intravital fluorescence microscope. After injection of the leucocyte marker acridine orange (1 mol/kg), six pericentral fields were observed for 30 s and experiments were recorded continuously. The percentage of perfused sinusoids was reduced in the livers in the EC group (82.9%) in contrast to the UW (93.2%) and HTK groups (91.0%). Livers in the EC group showed a reduction in the diameters of pericentral sinusoids (7.3±0.2 m; mean±SEM) compared with the UW group (9.5±0.2 m; P<0.05) and HTK group (10.2±0.8 m; P<0.05), indicating substantial cell swelling in livers stored in EC solution. Permanent adherence of leucocytes was most frequently observed in the EC group (33.5±1%), while this phenomenon was less pronounced in the UW group (14.5+1.1%; P<0.05) and HTK group (16.3±0.7%; P<0.05). Conversely, temporary adherence of leucocytes was reduced in the EC group (19.7+1.3%) compared with the UW group (30.5+2.1%) and the HTK group (34.4+0.8%). Microcirculatory failure and cell swelling in the EC group might be due to the lack of osmotic substances or oxygen radical scavengers included in UW (allopurinol, glutathione) and HTK (mannitol) solutions. In conclusion, cold storage of livers in UW and HTK solutions results in better preservation of the microcirculation and prevention of adhesion of leucocytes after transplantation compared with the EC solution.     

A comparison of histadine lactobionate solution with University of Wisconsin solution for rat liver and heart preservation

We developed a new solution mainly composed of Na-lactobionate and histidine (HL) and compared the effectiveness of this solution with that of University of Wisconsin (UW) solution using orthotopic liver and heterotopic heart transplantation in rats. The new solution has a higher sodium content and a lower potassium content (Na, 90 mEq/l; K, 45 mEq/l) than UW. Hydroxyethyl starch, adenosine, dexamethasone and insulin are not included. Buffering capacity is increased by adding histidine (90 mm/l) together with KH₂PO₄ (20 mm/l). Rat liver was perserved in either UW or HL solution hypothermically for 24 h and then transplanted orthotopically into the recipient rat. The heart was preserved in either solution for 18 h and transplanted heterotopically into the recipient rat. The 1-week survival rate for rats receiving livers preserved in UW for 24 h at 4°C was 29% (5/17). In contrast, the new solution (HL) gave a 78% (11/14) survival rate (P < 0.01). The 1-week heart graft survival rate, using UW solution was 50% (3/6), following 18-h cold preservation, whereas all hearts (7/7) continued to beat for over a week using new HL solution (P < 0.05). These results demonstrated that the new HL solution, with a substantial buffering capacity, was superior to UW solution in rat liver and heart preservation.     

The use of the University of Wisconsin (UW) and Euro-Collins (EC) solutions either alone or in a combined method

From June 1988 to October 1990, a total of 100 orthotopic liver transplantations (OLTs) in 91 patients were performed at the Hospital Clínic of Barcelona. Euro-Collins (EC) solution was used as the flush and storage solution in 29 livers, and the University of Wisconsin (UW) solution was used in 24. A combined method, consisting of flushing and harvesting the liver with UW solution through the portal vein and with EC solution through the aorta, was used in the remaining 47 livers. Livers harvested using such a combined method showed substantially better postoperative function in terms of AST, ALT, and prothrombin activity than those harvested in EC solution alone. Although AST and ALT values were lower in patoents whose livers were harvested using the combined method than with UW alone, differences were not significant. On the other hand, prothrombin activity was consistently better in the UW group. Bilirubin levels, platelet count, and bile output showed no difference among the three groups. We conclude that the combined use of UW and EC solutions for flushing and harvesting is not hazardous to human liver preservation and, in fact, may considerably reduce the amount of UW solution needed and, consequently, the costs.Preliminary results from this study were presented at the First International Congress of the Society for Organ Sharing in Rome in June 1991 and will also appear in Transplantation Proceedings.     

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.     

Histidine–Tryptophan–Ketoglutarate (HTK) Is Associated with Reduced Graft Survival in Deceased Donor Livers, Especially Those Donated After Cardiac Death

Single-center studies have reported that liver allograft survival is not affected by preservation in histidine–tryptophan–ketoglutarate (HTK) versus University of Wisconsin (UW) solution. We analyzed the UNOS database of liver transplants performed from July, 2004, through February, 2008, to determine if preservation with HTK (n = 4755) versus UW (n = 12 673) impacted graft survival. HTK preservation of allografts increased from 16.8% in 2004 to 26.9% in 2008; this was particularly striking among donor after cardiac death (DCD) allografts, rising from 20.7% in 2004 to 40.9% in 2008. After adjusting for donor, recipient and graft factors that affect graft survival, HTK preservation was associated with an increased risk of graft loss (HR 1.14, p = 0.002), especially with DCD allografts (HR 1.44, P = 0.025) and those with cold ischemia time over 8 h (HR 1.16, P = 0.009). Furthermore, HTK preservation was associated with a 1.2-fold higher odds of early (< 30 days) graft loss as compared to UW preservation (OR 1.20, p = 0.012), with a more pronounced effect on allografts with cold ischemia time over 8 h (OR 1.31, p = 0.007), DCD allografts (OR 1.63, p = 0.09) and donors over 70 years (OR 1.67, p = 0.081). These results suggest that the increasing use of HTK for abdominal organ preservation should be reexamined.     

Improved microcirculation by low‐viscosity histidine– tryptophan–ketoglutarate graft flush and subsequent cold storage in University of Wisconsin solution: results of an orthotopic rat liver transplantation model

As previously shown in a model of isolated rat liver perfusion, the combined use of an initial graft flush with low‐viscosity histidine–tryptophan–ketoglutarate (HTK) solution followed by cold storage in University of Wisconsin (UW) solution markedly improved the preservation during an extended cold storage period. In this study, we aimed to transfer our results into an in vivo model of orthotopic rat liver transplantation, and to elucidate the potential mechanism of the improved preservation by focusing on the hepatic microcirculation. Livers were harvested from male Wistar rats. Aortic perfusion with a pressure of 100 cm H₂O was performed with either UW (group UW) or HTK (groups UW and HTK_UW), followed by additional back‐table perfusion with UW (group HTK_UW). After 20‐h cold storage at 4 °C, livers were orthotopically transplanted with reconstructing the hepatic artery. As measured by bile flow and liver enzymes, HTK flush followed by UW storage was superior compared to single use of either UW or HTK solution. The hepatic microcirculation was significantly improved, as shown by the increased percentage of reperfused sinusoids and reduced sinusoidal leucostasis. HTK and UW effectively reduce ischaemia‐reperfusion injury after liver transplantation. By combining the comparative advantages of both solutions, a cumulative effect resulting in an improved preservation was shown. Thus, this mechanism improves microcirculatory reperfusion.     

Histidine-Tryptophan-Ketoglutarate (HTK) Is Associated with Reduced Graft Survival in Pancreas Transplantation

Prior single-center studies have reported that pancreas allograft survival is not affected by preservation in histidine-tryptophan-ketoglutarate (HTK) versus University of Wisconsin (UW) solution. To expand on these studies, we analyzed the United Network for Organ Sharing (UNOS) database of pancreas transplants from July 2004, through February 2008, to determine if preservation with HTK (N = 1081) versus UW (N = 3311) impacted graft survival. HTK preservation of pancreas allografts increased significantly in this time frame, from 15.4% in 2004 to 25.4% in 2008. After adjusting for other recipient, donor, graft and transplant center factors that impact graft survival, HTK preservation was independently associated with an increased risk of pancreas graft loss (hazard ratio [HR] 1.30, p = 0.014), especially in pancreas allografts with cold ischemia time (CIT) ≥12 h (HR 1.42, p = 0.017). This reduced survival with HTK preservation as compared to UW preservation was seen in both simultaneous pancreas-kidney (SPK) transplants and pancreas alone (PA) transplants. Furthermore, HTK preservation was also associated with a 1.54-fold higher odds of early (<30 days) pancreas graft loss as compared to UW (OR 1.54, p = 0.008). These results suggest that the increasing use of HTK for abdominal organ preservation should be re-examined.     

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。