腹主动脉联合门静脉快速灌注法在器官捐献供体肝肾联合获取中的应用

目的总结腹主动脉联合门静脉快速灌注法在器官捐献供体肝肾联合获取中的可行性和安全性。方法回顾性分析2011年9月至2014年6月在佛山市第一人民医院完成的43例中国心脏死亡供体器官捐献肝肾联合获取的临床资料。43例供体中,中国心脏死亡供体分类一类(脑死亡供体)(C-Ⅰ类)15例,中国二类(心脏死亡供体)(C-Ⅱ类)1例,中国三类(脑-心双死亡捐献供体)(C-Ⅲ类)27例。器官灌注采用腹主动脉、门静脉快速插管联合灌注法。结果开腹至腹主动脉插管时间约1.5~2.0 min,43例供体共获得肝脏43个,肾脏86个。C-Ⅰ类供体热缺血时间全部为0,其余供体热缺血时间范围为3~21 min,平均10 min。2例供肝分别因肝门部严重损伤和重度脂肪肝弃用,18例供肾分别因肾结石、肾萎缩、术前血清肌酐水平较高、肾动脉粥样硬化严重、肾微小血管血栓、多发肾囊肿、外伤性肾破裂等原因弃用,供体器官总弃用率为16%。结论腹主动脉联合门静脉快速灌注法是器官捐献供体肝肾联合获取的简单、安全的方法。     

The isolated perfused porcine liver: assessment of viability during and after six hours of perfusion

Isolated liver perfusion was developed for the study of liver physiology and preservation. The recent development of new perfusion devices and appropriate liver preservation solutions prompted us to reconsider liver perfusion for the specific purpose of evaluating viability in terms of biochemical changes, paying special attention to modifications in the histological ultrastructure. Twenty-two isolated pig livers were perfused with autologous blood. Arterio-portal perfusions were carried out using an extracorporeal perfusion circuit with a hollow fibre membrane oxygenator. Four groups of pig livers were studied using three different liver flushing solutions [Ringer's lactate, ELOHES, and University of Wisconsin (UW)] and two different oxygenation modalities. Liver function tests and histological studies were done. Our results revealed that a high partial oxygen pressure (PO₂) level was deleterious to the ultrastructural elements of hepatocytes, in particular to the mitochondria. It was also associated with deficient metabolic performance, i. e., poor bile production and lack of aerobic metabolism. Normal blood gas values could be obtained with the use of air for liver oxygenation. Flushing of the liver with Ringer's lactate or a macromolecular solution such as ELOHES was associated with severe liver cell injuries, as reflected by a marked rise in liver enzymes and histological lesions. Satisfactory results were obtained when UW solution was used for liver harvesting. We conclude that an appropriate liver preservation solution, normal blood gas values, and normal physiological arterio-portal pressure and blood flow are essential for appropriate liver function with preservation of liver architecture and of hepatocyte ultrastructures. Total bilirubin in bile and Factor V are sensitive indicators of good liver function. Received: 24 January 1997 Received after revision: 18 April 1997 Accepted: 24 April 1997     

Role of oxygen during hypothermic machine perfusion preservation of the liver

Grafts from non‐heart‐beating donors are thought to be best preserved by hypothermic machine perfusion (HMP). Controversy exists concerning the role of oxygenation during HMP. In this study, we wanted to evaluate the relative role of oxygenation for graft integrity during and after HMP. Cardiac arrest was induced in male Wistar rats (250–300 g) by phrenotomy. Thirty minutes later, livers were flushed via the portal vein and subjected to 18 h of HMP at 5 ml/min at 4 °C. During HMP, the preservation solution was equilibrated with 100% oxygen (HMP100), with air (HMP20) or not oxygenated at all (HMP0). Graft integrity was assessed thereafter upon warm reperfusion in vitro. During preservation, oxygenation of the perfusate reduced alanine aminotransferase release by 50% compared with HMP0. HMP100 resulted in reduced oxygen free radical‐mediated lipid peroxidation upon warm reperfusion compared with both HMP20 and HMP0. One hundred per cent oxygenation during HMP also significantly enhanced the activation of AMPK salvage pathway, and upstream activation of protein kinase A when compared with HMP0. Enzyme release during reperfusion was reduced by approximately 40% (HMP20) or approximately 70% (HMP100) after oxygenation compared with HMP0. Functional recovery (bile production) was only enhanced by HMP100 (approximately twofold increase vs. HMP20 and HMP0, P < 0.05). Efficiency of HMP might be markedly increased by additional aeration of the perfusate, most successfully by equilibration with 100% oxygen.     

Combined liver and kidney transplantation

Patients with end-stage renal and hepatic failure may be treated with combined liver and kidney transplantation (CLKTx). We reviewed the indications and outcomes of 16 CLKTx performed at the University of Minnesota between 1980 and 1994. The majority of the recipients (87.5%) were young patients affected by congenital hepatic anomalies and concomitant end-stage renal failure. Fourteen were treated with cyclosporin-based immunosuppression and had an excellent outcome: with an average of 6 years of follow-up, patient survival was 85.7%, liver graft survival 85.7%, and kidney graft survival 72%. The incidence of rejection episodes was similar to the rate of rejection in our solitary kidney and liver transplants. In conclusion, our experience supports the value of CLKTx in treating patients with simultaneous failure of both organs or with congenital enzymatic hepatic deficits leading to renal failure.     

机器灌注在心脏死亡捐献供肾保存中的应用进展

机器灌注在保存心脏死亡捐献(DCD)供肾过程中,比单纯静态冷保存具有更多的优越性。随着我国DCD供肾的应用,机器灌注已受到各大移植中心的重视,并越来越多地应用于捐献器官的保存。本文就机器灌注的工作原理、机制及在保存DCD供肾过程中的应用研究进展作一综述。     

Effects of cold ischemia and reperfusion on trapping of erythrocytes in the rat kidney

Abstract. After reperfusion of kidneys subjected to a period of warm ischemia, the medulla displays a vascular congestion of erythrocytes, especially in the inner stripe of the outer zone, a phenomenon referred to as "trapping." This trapping causes reflow alterations, thus contributing to postperfusion medullary ischemia. The purpose of the present investigation was to study whether trapping also occurs after reperfusion of kidneys following varying periods of cold ischemia and to determine if there is any correlation between the degree of cold ischemic injury and the extent of erythrocyte trapping. Rat kidneys stored at +4°C for 0–30 h were transplanted into recipient animals pretreated with a ⁵¹Cr-labelled erythrocyte suspension. Twenty minutes after reperfusion, the grafts were removed and microdissected into cortex, outer and inner stripes of the outer medullary zone, and inner zone, respectively. The radioactivity of these specimens was measured, and the erythrocyte content for each specimen was calculated. The results show a maximal trapping for cold ischemia time (CIT) of about 12–15 h. A linear correlation between the amount of trapping and CIT could be found in all parts of the kidney (except for the cortex) for CIT 0–15 h. The best correlation was found in the part where the trapping was most prominent, i.e., in the inner stripe. After CIT of 15 h or more, no correlation could be found. It is suggested, as described in models of warm ischemia, that the obstructions of the capillaries by trapped erythrocytes following reperfusion is of pathophysiological significance for the development of post-transplant acute renal failure. Furthermore, the strong correlation between CIT and the extent of erythrocyte trapping, particularly in the inner stripe, indicates that measurement of erythrocyte trapping after reperfusion could be a sensitive indicator of the degree of cold ischemic damage.     

Effects of cold ischemia and reperfusion on trapping of erythrocytes in the rat kidney

After reperfusion of kidneys subjected to a period of warm ischemia, the medulla displays a vascular congestion of erythrocytes, especially in the inner stripe of the outer zone, a phenomenon referred to as trapping. This trapping causes reflow alterations, thus contributing to postperfusion medullary ischemia. The purpose of the present investigation was to study whether trapping also occurs after reperfusion of kidneys following varying periods of cold ischemia and to determine if there is any correlation between the degree of cold ischemic injury and the extent of erythrocyte trapping. Rat kidneys stored at+4°C for 0–30 h were transphanted into recipient animals pretreated with a ⁵¹Cr-labelled erythrocyte suspension. Twenty minutes after reperfusion, the grafts were removed and microdissected into cortex, outer and inner stripes of the outer medullary zone, and inner zone, respectively. The radioactivity of these specimens was measured, and the erythrocyte content for each specimen was calculated. The results show a maximal trapping for cold ischemia time (CIT) of about 12–15 h. A linear correlation between the amount of trapping and CIT could be found in all parts of the kidney (except for the cortex) for CIT 0–15 h. The best correlation was found in the part where the trapping was most prominent, i.e., in the inner stripe. After CIT of 15 h or more, no correlation could be found. It is suggested, as described in models of warm ischemia, that the obstructions of the capillaries by trapped erythrocytes following reperfusion is of pathophysiological significance for the development of posttransplant acute renal failure. Furthermore, the strong correlation between CIT and the extent of erythrocyte trapping, particularly in the inner stripe, indicates that measurement of erythrocyte trapping after reperfusion could be a sensitive indicator of the degree of cold ischemic damage.     

MELD-Na评分对逆行灌注法原位肝移植术后早期急性肾损伤发生的预测作用

目的  探讨术前终末期肝病模型联合血清钠（MELD-Na）评分对肝移植术后早期急性肾损伤（AKI）发生率的预测效果。方法  回顾性分析315例行经下腔静脉逆行灌注法原位肝移植受者的临床资料。根据术前MELD-Na评分,将患者分为3组：A组为MELD-Na评分≤ 10分（115例）;B组为10分20分（82例）。比较3组受者术前、术中各项指标。术前指标包括血清肌酐（Scr）、血尿素氮（BUN）、白蛋白（Alb）、总胆红素（TB）、凝血酶原时间国际标准化比值（PT-INR）、平均动脉压（MAP）、血清Na⁺等;术中指标包括手术时间、腔静脉阻断时间、出血量、输红细胞量、输血浆量、总补液量等。统计3组受者肝移植术后早期AKI的发生率及分期情况,并采用Spearman等级相关分析术前MELD-Na评分与AKI分期之间的关系。结果  3组受者术前BUN、Alb、TB、PT-INR、MAP、Na⁺比较,差异均有统计学意义（均为P < 0.05）,术中的腔静脉阻断时间、出血量、输红细胞量、输血浆量比较,差异亦均有统计学意义（均为P < 0.05）。315例肝移植受者,术后早期1周内AKI发生率64.8%（204/315）,其中A、B、C组术后AKI发生率分别为43%（49/115）、71%（84/118）、87%（71/82）,3组间比较差异有统计学意义（P < 0.05）。经Spearman等级相关分析,术前MELD-Na评分与AKI分期存在正相关（r=0.442,P=0.000）。结论  MELD-Na评分不仅可以作为术前病情评估指标,也是术后发生AKI的重要预测指标。     

The value of myocardial perfusion imaging in screening coronary artery disease before kidney transplantation

The value of myocardial single-photon emission computed tomography (SPECT) in pre-transplant evaluation of kidney transplant recipients is controversial. We assessed whether myocardial SPECT predicts major adverse cardiac events (MACE) and determined whether SPECT findings affected transplant recipients' medical and invasive treatment. We analyzed 301 patients referred for myocardial SPECT before kidney transplantation and combined the results with information from patient files and the Transplantation Registry. During the median follow-up time of 96 months (IQR 70.75-118.25 months), the incidence of MACE was higher in patients (n = 37) with severely abnormal SPECT (>10% reversible perfusion defect) than in patients (n = 35) with mildly abnormal or normal SPECT (51.4%, 29.4%, and 27.0%, respectively, P = .011). Severely abnormal SPECT findings predicted long-term MACE in a univariable analysis but not after adjusting for other risk factors. Following SPECT, 29 patients (9.6%) underwent coronary angiography and 14 (4.6%) were revascularized. New antithrombotic or statin medication was prescribed to 7.3% of patients with ischemia in SPECT. Kidney transplantation patients are at high long-term risk of MACE even with normal preoperative myocardial SPECT. Abnormal SPECT did not predict MACE when adjusted for other risk factors. Minority of the patients underwent coronary revascularization or had changes in preventive medication before transplantation.     

重视供肝机械灌注研究,推动肝移植高质量发展

随着器官捐献数量不断增加和扩大标准供者(ECD)供肝定义不断拓展,供肝质量必然成为影响肝移植高质量发展的突出问题,也是相关领域的研究重点.最大限度解决器官短缺和推动器官移植高质量发展是我国器官捐献与移植事业发展的方向.近年来,利用机械灌注(MP)对供肝进行灌注、保存、评估及修复,已成为当前国际上提高肝移植质量的研究热点...     

肾脏常温机械灌注与无缺血肾移植

为了增加扩大标准供者(ECD)肾脏的利用率,肾脏保存方法近年来在不断发展。常温机械灌注(NMP)的使用,促进了离体供肾保存、评估和修复,以及肾移植手术方式革新。中山大学附属第一医院器官移植中心首创的无缺血肾移植(IFKT)手术,利用肾脏NMP机器在供肾获取、保存、移植全过程中,保持供肾血流和供氧不中断,从根本上避免了供肾缺血-再灌注损伤(IRI),降低了术后移植物功能延迟恢复(DGF)和急性排斥反应发生的风险。本文着重总结肾脏NMP的新进展,以及IFKT手术方式和近期疗效,旨在为提高ECD供肾利用率、解决器官短缺的问题提供参考。     

肝肾联合切取对移植肾质量的影响和技术探讨

目的 探讨肝肾联合切取对供肾质量的影响和技术改进。方法 比较59例肝肾联合切取供肾肾移植受者和152例单独肾脏切取肾移植受者近期肾功能的差异。结果 肝肾联合切取组受者术后急性肾小管坏死发生率为10．2％,术后第4天血肌酐值平均为262μmol/L,肾脏单独切取组受者分别为0．7％和162μmol/L,两组间比较差异有显著性。结论 肝肾联合切取对供肾质量有不良影响,操作过程中应注意保护供肾。     

常温机械灌注在无缺血肝移植中的应用体会

目的探讨常温机械灌注在无缺血肝移植手术中的应用体会。方法选取我院2017年7月23日~2017年8月25日应用常温机械灌注行无缺血肝移植的患者6例,术前做好人员准备、捐献供体准备、肝移植受体准备、环境和物品准备、器械和设备准备、机械灌注系统准备;术中配合医生完成无缺血供肝获取、无缺血供肝保存及无缺血肝移植手术。结果 6例供体肝脏均成功实施了无缺血器官获取术,手术时间3~4 h,平均3.5 h。器官机械灌注保存过程顺利,未发生异常。接着成功完成了6例全球首创不中断血流肝移植手术,手术过程顺利,手术时间5~7 h,平均6 h,手术出血600~2000 mL,平均1400 mL。结论常温机械灌注系统在无缺血肝移植手术中应用安全有效,术前准备充分,术中娴熟准确的护理配合是手术成功的基础和保障。