生理盐水替代HTK保存液保存活体供肾的临床研究

目的 探讨生理盐水替代组氨酸-色氨酸-酮戊二酸(histidine-tryptophan-ketoglurate,HTK)保存液对活体移植肾功能恢复的作用及可行性.方法 亲属活体供肾肾移植的患者82例,按患者意愿分为生理盐水组(29例)和HTK组(53例).生理盐水组用生理盐水作为移植肾灌注液,HTK组用HTK保存液作...     

Post-ischemia normal function of living related kidney transplants after preservation with HTK solution

This study reports on the first clinical use of HTK preservation solution devised by Bretschneider in renal transplantation. Using this HTK solution, nine living related donor kidneys subjected to cold ischemia for up to 4 h were consecutively transplanted between 1987 and 1989. The postoperative function of the donor and recipient kidneys is analyzed. The endogenous creatinine clearance and the plasma creatinine level are used as function parameters. Within 24-48 h after transplantation a postischemic normal graft function occurred. With triple drug therapy the transplanted kidneys showed an increase in renal function identical with that in the donor's single remaining kidney. Within 7 postoperative days no perfusion damage and no HTK or CyA nephrotoxicity was observed.     

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.     

Ultrastructural findings during human myocardial preservation with HTK solution

Although the majority of recent scientific advances developed in the field of myocardial preservation have improved surgery procedures, it seems that during cardiothoracic surgery ischemia-reperfusion continues triggering clinical postoperative problems. This report focused on the changes human capillary endothelial cells and nerve endings suffer after cardiopulmonary bypass. The study involved four patients who received Bretschneider solution for cardioplegia during mitral stenosis surgery. Biopsies of right atrium were taken prior to and after CPB to be analyzed under electron microscopy. Samples taken after CPB showed detachment of myocardial capillary basal membrane, endothelial edema, and widespread nerve-ending destruction. Nevertheless, the shelter provided by the most advanced cardioplegic solutions, myocardial endothelial edema, and nerve-ending destruction cannot be completely prevented. Thus, it is possible to suggest that low interstitial concentration of Na(+), which activates Na(+)/Ca(++) exchanger, and inflow of Ca(++), present during ischemia-reperfusion, may lead to endothelial and neuronal cell damage, triggering cardiac contraction dysfunction. This mechanism would explain at least in part some of the problems patients face during the postoperative state.     

Pulmonary preservation with Bretscheider''s HTK and Celsior solution in minipigs

Background: Pulmonary preservation with high potassium/low oncotic pressure Euro-Collins (EC) solution is associated with endothelial dysfunction and reduced surfactant function. We compared two low potassium solutions, histidine-tryptophane-ketoglutarate (HTK) and Celsior, to EC in lung ischemia-reperfusion injury. Methods: In 19 minipigs, the left lung was perfused in situ with cold preservation solution (EC, n=6; HTK, n=6; Celsior, n=7). Reperfusion was started after 90 min of warm ischemia. The right pulmonary artery and main bronchus were clamped. Bronchoalveolar lavage (BAL) was obtained before ischemia and after 2 h of reperfusion. Surfactant activity was determined from the BAL in a pulsating bubble surfactometer. Results: Animals in the EC group survived 3.7±1.4 h. Six Celsior and five HTK treated animals survived the observation period of 7 h (P<0.001). Compliance of the reperfused lung deteriorated less in both Celsior and HTK groups (P<0.001). In EC and HTK animals, the pO₂/FiO₂ ratio was lower (P=0.002), and pulmonary vascular resistance was higher (P=0.02) than in Celsior animals. Surfactant function was impaired after reperfusion in all groups. Conclusions: Compared to EC, HTK solution showed moderate and Celsior distinct improvement of post-ischemic pulmonary function. However, surfactant function was not well preserved in any group.     

保证活体肝移植供、受者安全的几个问题

目前,能有效治疗终末期肝病的惟一方法是进行肝移植,但长期以来供肝短缺一直是困扰国际肝移植界的一大难题.近年来,活体供肝移植(LDLT)的兴起缓解了供肝短缺这一矛盾.     

活体肝移植供体的安全性

早期活体肝移植主要应用于儿童受体，供肝切取量较小，并发症发生率低，供体安全性很快得到确认。此后，有学者总结了活体肝移植的经验，建立了开展活体肝移植的三条基本原则，即波士顿标准：（1）对于受者具有显著的成功率；（2）对于供者低风险；（3）供者的知情同意。迄今为止，波士顿标准仍然是指导活体肝脏移植开展的基本原则，促使活体肝移植在充分保障供体安全的前提下，逐步应用于成人终末期肝病的治疗。[第一段]     

Safety of donor right hepatectomy for adult-to-adult living donor liver transplantation

The purpose of this study was to ascertain the usefulness of preoperative evaluations of donors by computed tomography (CT) volumetry and CT cholangiography for prevention of unexpected liver failure and biliary complications after donor right hepatectomy for adult-to-adult living donor liver transplantation. Fifty-two donors who underwent right hepatectomy without the middle hepatic vein were enrolled in this study. The values of graft weight (GW) were significantly correlated with those of estimated graft volume (GV; P < 0.0001). GW was predicted by the following formula: GW = 155.25 + 0.658 x GV; r(2) = 0.489. CT cholangiography revealed anatomical variants of biliary structure in one-third of the donors and also clearly showed one or two small biliary branches from the caudate lobe to the right hepatic ducts or the confluence in 58% of the donors. Biliary leakage, which was treated by conservative therapy, occurred in only one donor (1.9%). No donors received homologous blood transfusion. Hyperbilirubinemia (serum total bilirubin >5 mg/dl) occurred in 5.8% of the donors during their early postoperative periods. Precise evaluations of liver remnant volume by CT volumetry and biliary variation by CT cholangiography are essential for performing safe donor hepatectomy, preventing hepatic insufficiency and minimizing the risk of biliary tract complications.     

活体右半肝供体的安全性

目的 探讨活体右半肝供体的安全性。方法 对2002年1月至2005年6月施行的13例活体右半肝移植中供体的资料进行回顾性研究。不阻断入肝血流,在肝中静脉右侧,用超声刀离断肝组织得到右半供肝。通过计算得到标准肝体积及残余左半肝的比例。结果 右半供肝切取术平均失血490ml,平均输血440ml。围手术期平均输入人血白蛋白85g。1例供体门静脉分为3支,2例供体右后与右前胆管汇入左肝管,1例左外与左内胆管先后与右肝管汇合成肝总管,术中处理恰当,门静脉左干血流及左肝管胆汁引流保持通畅。2例供肝轻度脂肪变。术后第1天肝功能均有不同程度损害,但术后1周恢复到接近正常水平。术后并发症包括1例腹腔内出血,2例切口脂肪液化和1例乳糜漏。所有供体恢复好并回到原工作岗位。结论 只要保证左半肝血管与胆管通畅,残余肝体积在30％以上及手术对残余肝无大的损伤,右半供肝切取是安全的。     

Safety of right lobectomy in living donor liver transplantation

The goal of this study was to examine the safety and effectiveness of right lobectomy in living donor liver transplantation (LDLT). From January 1999 to January 2002, 100 cases of LDLT were performed at Seoul National University Hospital; 45 involved right lobectomy (RL), 17 involved extended left lobectomy (ELL), 37 involved left lateral segmentectomy (LLS), and 1 involved right posterior segmentectomy. The outcome of RL was compared with those of other types of hepatectomy. An RL resulted in a longer operative time (minutes) than an LLS (349.0 ± 65.1 versus 286.7 ± 54.0, P < .01), but not an ELL (351.2 ± 84.3, P =.99). The hospital stay (days) in the RL group (14.4 ± 3.1) was longer than for those in the ELL group (11.7 ± 1.7, P < .01) and the LLS group (11.7 ± 1.9, P < .01). The drain amount (mL) of the postoperative third day in the RL group (194.4 ± 143.4) was larger than for those in the ELL group (56.8 ± 84.1, P < .01) and the LLS group (46.5 ± 39.6, P < .01). The postoperative peak serum level of total bilirubin (mg/dL) was 3.0 ± 1.5 in the RL group, 1.9 ± 0.7 in the ELL group, and 1.9 ± 0.9 in the LLS group (P < .01, RL versus LLS, ELL). There was no mortality or major morbidity and no reoperation of donors. Right lobectomy is a relatively safe and effective procedure in LDLT, but brings more potential risks and morbidity in donors. (Liver Transpl 2002;8:910-915.)     

Morphological investigation of the porcine liver directly following preservation with Euro-Collins,University of Wisconsin and Bretschneider's HTK solution

Zusammenfassung Zur Klärung der Frage, ob unter der Anwendung verschiedener Verfahren zur Leberkonservierung strukturell nachweisbare perfusionsbedingte Schäden auftreten können, wurden Lebern von Schweinen mit a) HTK-Lösung nach Bretschneider (Histidin-Tryptophan-Ketoglutarat), b) Euro-Collins-Lösung (EC), c) University of Wisconsin-Lösung (UW) entsprechend den Anweisungen des Herstellers perfundiert. Anschließend wurden alle Organe zusammen mit unprotelctionierten Lebern licht- und elektronenmikroskopisch unter Einschluß computergestutzter morphometrischer Analysen untersucht. Die Kontinuität der Sinusendothelzellen, die Weite des Disseschen Raumes sowie die Ultrastruktur der Hepatozyten wurden primär durch keines der protektiven Verfahren beeintrdchtigt. Beträchtliche Unterschiede wurden aber hinsichtlich der Ausspülung des Blutes festgestellt. Die mit der HTK-Lösung perfundierten lebern waren mit Abstand am besten von korpuskulären Blutbestandteilen befreit, gefolgt von EC-und UW-Lebern. Mittels eines computerunterstützten Morphometrieverfahrens konnten keine signifikanten Größenunterschiede zwischen den Hepatozyten der EC-, UW- and HTK-Gruppe festgestellt wurden. Lediglich die Hepatozyten der normothermen Kontrollebern waren um 10% größer als diejenigen in den mit den 3 protektiven Lösungen perfundierten Organen. Es ergaben sich unter keinem der drei Protektionsverfahren strukturelle Anhaltspunkte für einen Perfusionsschaden.Supported by the Deutsche Forschungsgemeinschaft, SFB 330 -Organprotektion     

Safety of donor in adult-to-adult living donor liver transplantation using right lobe graft

BACKGROUND: The growing gap between the number of patients awaiting liver transplantation and available organs has continued to be the primary issue facing the transplant community. To overcome the waiting list mortality, living donor liver transplantation has become an option, in which the greatest concern is the safety of the donor, especially in adult-to-adult living donor liver transplantation (A-A LDLT) using a right lobe liver graft. OBJECTIVE: We evaluated the safety of donors after right lobe liver donation for A-A LDLT performed in our center. METHODS: From January 2002 to March 2006, 26 patients underwent A-A LDLT using right lobe liver grafts in our center. Seven donors were men and 19 were women (range, 19-65 years; median age, 38 years). The right lobe liver grafts were obtained by transecting the liver on the right side of the middle hepatic vein without interrupting the vascular blood flow. The mean follow-up time for these donors was 9 months. RESULTS: These donor residual liver volumes ranged from 30.5% to 60.3%. We did not experience any donor mortality. Two cases (7.69%) experienced major complications: intra-abdominal bleeding and portal vein thrombosis in one each and three (11.54%), minor ones: wound steatosis in two, and transient chyle leak in one. All donors were fully recovered and returned to their previous occupations. CONCLUSIONS: A-A LDLT using a right lobe liver graft has become a standard option. The donation of right lobe liver for A-A LDLT was a relatively safe procedure in our center.     

HTK-N, a modified HTK solution, decreases preservation injury in a model of microsteatotic rat liver transplantation

Background

Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) solution, HTK-N, has been developed. This solution contains N-acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury.

Methods

Microvesicular steatosis was induced by a single dose of ethanol (8?g/kg BW). Livers were harvested and stored at 4?°C for 8?h with HTK or HTK-N before transplantation. Tissue and blood samples were taken at 1, 8, and 24?h after reperfusion to compare serum liver enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), standard histology, and immunohistochemistry for myeloperoxidase (MPO), caspase-3, and inducible nitric oxide synthase. Survival was compared after 1?week. For statistics, Analysis of Variance and t test were used.

Results

HTK-N improved survival from 12.5?% in HTK to 87.5?% (p?<?0.05). Furthermore, liver enzymes were decreased to 2?C75?% of HTK values (p?<?0.05). Necrosis and leukocyte infiltration and MPO, caspase-3, and iNOS expression after transplantation were decreased (p?<?0.05).

Conclusions

This study demonstrates that HTK-N protects liver grafts with microvesicular steatosis caused by acute toxic injury from cold ischemic injury better than standard HTK most likely via inhibition of hypoxic injury and oxidative stress and amelioration of the inflammatory reaction occurring upon reperfusion.     

The renal-sparing efficacy of basiliximab in adult living donor liver transplantation.

The purpose of this study is to find out whether basiliximab administration will improve postoperative renal function by delaying the start of tacrolimus and decreasing of dosage requirement for tacrolimus in adult living donor liver transplantation (LDLT). Forty-five adult LDLT recipients were enrolled in the study. The induction group (n = 27) was given basiliximab 20 mg on days 0 and 4; tacrolimus administration was delayed until renal function improved. The control group (n = 18) did not receive basiliximab; tacrolimus was given on the first postoperative day. Trough levels of tacrolimus in the induction and control groups were aimed to be maintained at 5-10 ng/ml and 10-15 ng/ml during the first week after transplant, respectively. The median follow-up was 22 months (range 10-34 months). The preoperative conditions were poorer in the induction group (Child C, 56% vs. 33%, P = 0.01; UNOS 2a, 15% vs. 0%, P = 0.02). The intraoperative blood loss was also higher in the induction group than in the control group (median 2,180 ml vs. 495 ml, P < 0.01). The median delay in tacrolimus administration in the induction group was 36 hours (range 24-108 hours). Serum creatinine levels at second and third postoperative months were significantly lower in the induction group. The creatinine clearance rate in the induction group was higher at the third month posttransplant (median 72 vs. 57 ml/minute, P = 0.04). The incidence of renal insufficiency was significantly lower in the induction group at the third month posttransplant (26% vs. 67%, P < 0.01). Blood cholesterol level at the sixth month posttransplant was lower in the induction group (median 152 vs. 196 mg/dl P = 0.03). The incidences of acute cellular rejection, bacteremia, and cytomegalovirus (CMV) infection were similar in both groups. In conclusion, for pretransplant critical patients with more intraoperative blood loss, basiliximab induction could prevent early renal dysfunction by delaying the start of tacrolimus and reducing the dose requirement of tacrolimus without increasing graft rejection and infection. Furthermore, it also improved renal function as well as lowered cholesterol levels within 6 months after transplantation.