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.     

Effect of blood group matching on liver transplant survival rates

From the immunological standpoint,^1–5 liver allografts are more resistant to hyperacute rejection than are other solid organ grafts. Therefore, until recently, donor/recipient blood type (ABO type), human leukocyte antigen (HLA) matching, and crossmatch tests were not considered in clinical liver transplantation. In this report, we demonstrated that: (a) crossing the ABO barrier must be avoided except in extreme emergency; (b) HLA class I matching effect on liver allografts is as acceptable as in kidney transplantation, although, with regard to the effect of Class II matches, there are remarkable differences depending on the patients' original disease; and (c) anti-donor lymphocytotoxic antibodies (positive crossmatch) adversely affect liver allograft survival rates.     

Effects of cyclosporin A on the blood flow of the native and transplanted rat pancreas and duodenum

The aim of the present study was to evaluate the effects of cyclosporin A (CyA) on the blood perfusion of the transplanted pancreas. For this purpose syngeneic pancreaticoduodenal transplantations were performed in Wistar-Furth rats. After nephrectomy the graft was anastomosed using a nonsuturing cuff technique to the left renal vessels. Beginning 7 days after transplantation and then continuing for 2 weeks, CyA (15 mg/kg body weight) or vehicle was given p.o. once daily, 6 days a week. The serum CyA concentrations were greater than 600 ng/ml at all points in time tested. Intraperitoneal glucose tolerance tests were normal in CyA-treated animals after 12 days, but the pancreatic insulin concentration was decreased to the same extent in the native and transplanted pancreas. A microsphere technique was used to measure the blood perfusion of the pancreaticoduodenal graft, the native pancreas and duodenum, and remaining kidney 14 days after starting the CyA treatment. The renal blood flow was markedly decreased by CyA when compared with the control animals. In rats given vehicle alone, pancreatic, islet, and duodenal blood flows were higher in the graft than in the corresponding native organs. However, in rats given CyA, hyperperfusion of the graft was not observed. We conclude that the administration of CyA prevents the transplantation-induced blood flow increase seen in pancreaticoduodenal grafts of vehicle-treated rats. These observations may reflect graft denervation.     

供体抗原注入胸腺处理对大鼠胰腺移植功能存活的影响

在大鼠胰腺移植模型上将供体Ｗｉｓｔａｒ大鼠的脾细胞于移植前或移植时注入受体ＳＤ大鼠胸腺内，辅以短期免疫抑制剂，结果显示能明显延长胰腺移植物功能存活。崦单纯短期免疫抑制剂或单纯供体脾细胞注入胸腺均未能延长胰腺功能存活。提示供体脾细胞注入胸腺预处理延长胰腺功能存活效果优于移植时处理，但移植时处理可能更有实用价值。     

Success rate and impact of HLA matching on kidney graft survival in highly immunized recipients

From 1985 to 1990, 225 highly immunized recipients were transplanted based on a program of serum exchange and priority allocation of kidneys to crossmatch negative recipients. The 1-year graft survival rate in first transplant recipients was 73% and in second transplant recipients, 71 %. Recipients of third or fourth transplants had a 25 % lower success rate. HLA matching exerted a significant influence on graft outcome. Twenty-five first or second grafts with zero mismatches for HLA-B,-DR had a 91 % 1-year survival rate, in contrast to a 58% survival rate of 38 grafts with of three or four HLA-B,-DR mismatches (log rank P < 0.001).     

Postoperative recovery of mitochondrial function of the human liver graft procured and preserved with University of Wisconsin (UW) solution

Changes in arterial blood ketone body ratio (KBR) were investigated in 47 human liver transplantations. Of the 20 grafts preserved with University of Wisconsin (UW) solution, 10 had a cold preservation period of less than 10 h (UWS group) and 10 of more than 10 h (UWL group). In 27 other cases, grafts were preserved with EuroCollins (EC) solution for less than 10 h (EC group). In the EC group, KBR increased over 0.7 within 6 h after reperfusion of the graft in 17 cases (63%) and within 24 h in 7 cases (26%). In the 3 other cases, KBR failed to recover, and these patients underwent retransplantation. In the UW group, KBR recovered within 6 h in 13 cases (65%) and within 24 h in 7 cases (35%). There were no significant differences between the UWS and UWL groups. It is shown that the mitochondrial function of liver grafts preserved with UW solution can be well maintained even after extended preservation periods of more than 10 h.     

Interstitial and vascular pancreas rejection in relation to graft survival

To examine the incidence of interstitial and vascular rejection in pancreas allografts and its impact on graft survival, we studied 36 percutaneous pancreas biopsies and 10 pancreas transplantectomy specimens from 32 patients who had undergone simultaneous pancreas-kidney transplantation. Interstitial rejection (IR) was predominantly found in the biopsies, while vascular rejection (VR) was most prominent in the transplantectomies. Pancreas graft survival was significantly decreased for pancreas grafts that had suffered from vascular rejection when compared to those with only interstitial rejection. Potential rejection markers, i. e., serum amylase, glucose, creatinine, and urinary amylase, did not correlate with histological signs of rejection, although increased levels of serum amylase were, in all but one case, associated with rejection.We conclude that a percutaneous pancreas biopsy remains the most reliable method to determine pancreas rejection, and that by distinguishing between IR andVR, a pancreas biopsy may provide important diagnostic as well as prognostic information. Received: 6 March 1997 Received after revision: 5 June 1997 Accepted: 30 June 1997     

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.     

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.     

供体抗原经门静脉处理及移植物从门静脉回流对大鼠胰腺移植物功能存活的影响

以35只雄性SD大鼠为受体，制成糖尿病模型，以同龄Wistar雄性大鼠为供体，行全胰腺移植。供体抗原分别经门静脉或周围静脉处理，处理时间分别为移植前预处理或移植时处理，移植物静脉分别从门静脉或下腔静脉回流，结果表明供体抗原经门静脉预处理及移植物从门静脉回流对胰腺移植物功能存活的延长具有协同效应，移植时处理延长胰腺移植物效果不如移植前预处理，但可能具有一定的实用意义。     

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     

Influence of UW solution on in vitro platelet aggregability

Abstract  Bleeding problems in or-thotopic liver transplantation (OLT), starting immediately after reperfusion of the graft, are complicating the outcome of transplantation. Platelets may be involved in this situation, but there is still a lack of information about the influence of UW solution on platelet function. We evaluated the effect of UW solution on in vitro platelet aggreg ability in healthy volunteers using whole blood electrical aggregometry and concluded, that UW solution causes impaired platelet aggregabil ity and may contribute to bleeding problems during OLT. The mechanism of impairment remains un clear, since central pathways as well as membrane receptors seem to be involved. Furthermore. our data support the necessity of extended flushing of the liver graft after re perfusion.     

Prolonged rat pancreas preservation using a solution with the combination of histidine and lactobionate

A newly formulated solution consisting of lactobionate with or without histidine was tested in the preservation of the rat pancreas. Adult male Lewis rats weighing 120–250 g were used as donors and recipients. Fifty-four rat pancreas transplants were performed to investigate the effectiveness of this test solution and to compare it with the standard University of Wisconsin (UW) solution. The final osmolarity of the new test solution was 290–320 mosmol/l. This solution had a higher sodium content and lower potassium content (Na: 110 mEq/l, K: 50 mEq/l). Adenosine, insulin, hydroxyethyl starch and dexamethasone, which are components of the UW solution, were not present in this test solution. Histidine was used as a buffer. Rat pancreases were stored at 4 °C in either standard UW solution, or high-Na ⁺-histidine solution, or high-Na ⁺ -lactobionate solution for 48 h and 72 h prior to heterotopic transplantation into rats with streptozotocin-induced diabetes mellitus. Functional success rates for rats receiving pancreases that had been preserved in high-Na*-histidine and in high-Na ⁺-lactobionate solutions at 4°C were 100% (5/5) and 100% (7/7) after 48 h preservation, and 50% (4/8) and 14% (1/7) after 72 h preservation, respectively. By contrast, standard UW solution gave only a 44% (4/9) success rate after 48 h preservation and a 0% (0/8) success rate after 72 h preservation. These results demonstrated that the high-Na ⁺-histidine solution was superior to standard UW solution for rat pancreas preservation. This was probably due to the buffer, histidine, which prevented the acidosis of ischemic tissue during the period of preservation.     

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.     

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.     

HLA配型对移植肾功能恢复的影响

为了探讨ＨＬＡ配型对移植肾功能恢复的影响，对２５例肾移植患者术前进行了ＨＬＡ配型，术后测定内醇结合蛋白（ＲＢＰ）的含量来评价肾功能的恢复情况。结果表明，与血清肌酐相比，ＲＢＰ能更准确地反映肾功能的状态，ＨＬＡ有１个以上ＤＲ位点上配者，术后１个月有９／１１的患者ＲＢＰ低于原始值的１０％；有１个以上Ｂ位点相配者，术后１个月有７／８的患者ＲＢＰ低于原始值的１０％；而无呈仅有１个Ａ位点相配，主后１个月仅有     

Octreotide administration in the treatment of pancreatic fistulae after pancreas transplantation

Among the surgical complications of pancreas transplantation are pancreatic fistulae, which arise rather frequently. Suppression of exocrine secretion with polymers has succeeded in reducing the rate of this complication. Nevertheless, in some instances, pancreatic fistulas may occur. Thirty pancreas transplantations were performed in 27 diabetic patients. In 5 cases a pancreatic fistula occurred and was drained after the insertion of a catheter for the collection of secretions. A serous liquid was collected with a high concentration of amylases (61604±19562 IU/24h). Fistula output was 280 ±87 ml/24 h. Patients were treated with octreotide, administered subcutaneously in a dose of 300–750 g/day. In all patients a progressive reduction in fistula output was observed after a mean of 16+2 days. Fistula flow rate dropped to 24±10 ml/24 h-areduction of 95%±5% and drainage was subsequently stopped. Sonographic followup did not show recurrence of peripancreatic collections in these patients. All patients were insulin-independent up to 12–44 months after surgery.     

Effect of the surgical technique on long-term outcome of pancreas transplantation

To date there is no general consensus as to the best surgical technique for pancreas transplantation. Patients with a pancreas transplant functioning for 3 years or more were retrospectively investigated to compare three surgical techniques: segmental graft with duct obstruction (DO), whole graft with bladder drainage (BD), and whole graft with enteric drainage (ED). Several parameters were studied: patient and graft survival, rejection, long-term surgical and medical complications, and endocrine function. The best results in terms of graft survival and quality of metabolic control were obtained in the group that underwent whole graft transplantation with ED. At 3 years, overall pancreas graft survival was 65 % for ED, 60 % for BD, and 47 % for DO. This surgical method has become the preferred technique in our unit. Received: 9 October 1997 Received after revision: 29 January 1998 Accepted: 30 March 1998