Custodiol® Supplemented with Synthetic Human Relaxin Decreases Ischemia-Reperfusion Injury after Porcine Kidney Transplantation.

Objective. Ischemia-reperfusion injury (IRI) is inevitable after kidney transplantation (KT), impairing outcomes. Relaxin-2 (RLX) is a promising insulin-related peptide hormone that protects against renal IRI in rodents, although large animal models are needed before RLX can be tested in a human setting. Methods. In this blinded, randomized, and placebo-controlled experimental study kidneys from 19 donor pigs were retrieved after perfusion with Custodiol® ± RLX (5 or 20 nmol/L) and underwent static cold storage (SCS) for 24 and 48 h, respectively. Subsequently, KT was performed after unilateral right nephrectomy. Study outcomes included markers for kidney function, oxidative stress, lipid peroxidation, and endothelial cell damage. PCR analysis for oxidative stress and apoptosis-related gene panels as well as immunohistochemistry were performed. Results. RLX upregulated SOD2 and NFKB expression to 135% (p = 0.042) and 125% (p = 0.019), respectively, while RIPK1 expression was downregulated to 82% (p = 0.016) of corresponding controls. Further RLX significantly downregulated RIPK1 and MLKL expression and decreased the number of Caspase 3- and MPO-positive cells in grafts after SCS. Conclusions. RLX supplemented Custodiol® significantly decreased IRI via both antioxidant and anti-apoptotic mechanisms. Clinical trials are warranted to implement synthetic human RLX as a novel additive to preservation solutions against IRI.

Emerging role of carbon monoxide in intestinal transplantation.

Intestinal transplantation has become an established therapeutic option that provides improved quality of life to patients with end-stage intestinal failure when total parenteral nutrition fails. Whereas this challenging life-saving intervention has shown exceptional growth over the past decade, illustrating the evolution of this complex and technical procedure from its preclinical origin in the mid-20th century to become a routine clinical practice today with several recent innovations, its success is hampered by multiple hurdles including technical challenges such as surgical manipulation during intestinal graft procurement, graft preservation and reperfusion damage, resulting in poor graft quality, graft rejection, post-operative infectious complications, and ultimately negatively impacting long-term recipient survival. Therefore, strategies to improve current intestinal transplantation protocol may have a significant impact on post-transplant outcomes. Carbon monoxide (CO), previously considered solely as a toxic gas, has recently been shown to be a physiological signaling molecule at low physiological concentrations with therapeutic potentials that could overcome some of the challenges in intestinal transplantation. This review discusses recent knowledge about CO in intestinal transplantation, the underlying molecular mechanisms of protection during intestinal graft procurement, preservation, transplantation and post-transplant periods. A section of the review also discusses clinical translation of CO and its challenges in the field of solid organ transplantation.

Appraising 5 years in activity of the largest public Canadian vascular graft bank.

BACKGROUND: In Canada, tissue distribution is managed by provincial entities. In 2014, Hema-Quebec established a cryopreserved vascular tissue bank accessible to all Canadian hospitals. The objectives of this report were to review the first 5 years of activity of Hema-Quebec's vascular bank and to briefly assess the competitiveness of its products. METHODS: Deceased donors, ages 15 to 60, were screened for common blood-borne diseases. Grafts were treated in a triple-antibiotic solution at 35°C before preservation at -100°C. Hema-Quebec's vascular graft records were analyzed from 2014 to 2019 inclusively. RESULTS: The average donor age was 35 years old and 78% of donors were men. Overall, 63% of harvested grafts cleared the quality management system. Positive microbial cultures and morphologic defects were the major reasons for graft discard. As such, a total of 60 grafts were delivered between 2016 and 2019 to 8 hospital centers. Moreover, the bank achieved a mean activity increase of 55% per year and Hema-Quebec's homografts were 48% less costly compared with similar homographs from for-profit organizations. CONCLUSIONS: Our findings demonstrate that Hema-Quebec has established a viable cryopreserved vascular tissue bank with steady increase in activity and an acceptable graft discard rates and pricing. Based on our findings, we recommend that efforts should be directed to expand the tissue bank graft distribution outside the province of Quebec.

Protective Effects of a Hydrogen-Rich Preservation Solution in a Canine Lung Transplantation Model.

BACKGROUND: Molecular hydrogen (H2) has protective effects against ischemia-reperfusion injury in various organs. Because they are easier to transport and safer to use than inhaled H2, H2-rich solutions are suitable for organ preservation. In this study, we examined the protective effects of an H2-rich solution for lung preservation in a canine left lung transplantation (LTx) model. METHODS: Ten beagles underwent orthotopic left LTx after 23 hours of cold ischemia followed by reperfusion for 4 hours. Forty-five minutes after reperfusion, the right main pulmonary artery was clamped to evaluate the function of the implanted graft. The beagles were divided into two groups: control group (n = 5), and H2 group (n = 5). In the control group, the donor lungs were flushed and immersed during cold preservation at 4°C using ET-Kyoto solution, and in the H2 group, these were flushed and immersed using H2-rich ET-Kyoto solution. Physiologic assessments were performed during reperfusion. After reperfusion, the wet-to-dry ratios were determined, and histology examinations were performed. RESULTS: Significantly higher partial pressure of arterial oxygen and significantly lower partial pressure of carbon dioxide were observed in the H2 group than in the control group (P = .045 and P < .001, respectively). The wet-to-dry ratio was significantly lower in the H2 group than in the control group (P = .032). Moreover, in histology examination, less lung injury and fewer apoptotic cells were observed in the H2 group (P < .001 and P < .001, respectively). CONCLUSIONS: Our results demonstrated that the H2-rich preservation solution attenuated ischemia-reperfusion injury in a canine left LTx model.

Histidine-tryptophan-ketoglutarate solution versus University of Wisconsin solution in adult-to-adult living donor liver transplantation: A propensity score matching analysis from mainland China.

ABSTRACT: To compare the difference between University of Wisconsin (UW) solution and histidine-tryptophan-ketoglutarate (HTK) solution in adult living donor liver transplantation (LDLT).This study included LDLT patients at the Liver Transplantation Center of West China Hospital of Sichuan University from November 2001 to June 2018. These patients were classified into 2 groups depending on the use of the different preservation solutions, and the confounding factors between the 2 groups were eliminated by propensity score matching. Finally, the incidence of complications; serum examination at postoperative days 1, 3, 5, 7, 14, 21, and 30; and the overall survival rate of the 2 groups were compared to observe whether there were any differences between the 2 preservation solutions.Of the 298 patients we screened, 170 were treated with UW solution and 128 with HTK solution. After propensity score matching, 106 pairs of patients were selected. In the comparison of the 2 groups, the length of intensive care unit stay in the UW group was significantly longer than that in the HTK group (P = .022), but there was no difference in the total length of hospital stay between the 2 groups (P = .277). No statistically significant difference was observed in the 2 groups in terms of the incidence of complications or postoperative examinations. However, the incidence of early allograft dysfunction in the HTK group was slightly lower than that in the UW group (HTK: UW = 14.1%: 20.7%), although the difference was not statistically significant. In terms of the overall survival rate, the 1, 3, and 5-year survival rates of the HTK group were 85.5%, 70.2%, and 65.1%, respectively, while the 1, 3, and 5-year survival rates of the UW group were 83.1%, 67.2%, and 59.8%, respectively, and there was no significant difference between the 2 groups.In conclusion, our study shows that UW solution and HTK solution are equivalent in perioperative safety, the recovery of transplanted liver function, the occurrence of postoperative complications and overall survival and can be safely and effectively applied in adult LDLT. If economic factors are taken into account, HTK can save costs to a certain extent.

Ex-Vivo Normothermic Limb Perfusion With a Hemoglobin-Based Oxygen Carrier Perfusate.

INTRODUCTION: Ex-vivo normothermic limb perfusion (EVNLP) has been proven to preserve limb viability better than standard cold storage. Perfusates containing packed red blood cells (pRBC) improve outcomes when compared to acellular perfusates. Limitations of pRBC-based perfusion include limited availability, need for cross match, mechanical hemolysis, and activation of pro-inflammatory proteins. Hemoglobin-based oxygen carrier (HBOC)-201 (Hemopure) is a solution of polymerized bovine hemoglobin, characterized by low immunogenicity, no risk of hemolytic reaction, and enhanced convective and diffusive oxygen delivery. This is a preliminary study on the feasibility of EVNLP using HBOC-201 as an oxygen carrier. MATERIALS AND METHODS: Three porcine forelimb perfusions were performed using an established EVNLP model and an HBOC-201-based perfusate. The perfusion circuit included a roller pump, oxygenator, heat exchanger, and reservoir. Electrolytes, limb temperature, weight, compartment pressure, nerve conduction, and perfusion indicated by indocyanine green angiography and infra-red thermography were monitored. Histological evaluation was performed with hematoxylin and eosin and electron microscopy. RESULTS: Three limbs were perfused for 21.3 ± 2.1 hours. Muscle contractility was preserved for 10.6 ± 2.4 hours. Better preservation of the mitochondrial ultrastructure was evident at 12 hours in contrast to crystallization and destruction features in the cold-storage controls. CONCLUSIONS: An HBOC-201-EVNLP produced outcomes similar to RBC-EVNLP with preservation of muscle contractility and mitochondrial structure.

Do storage solutions protect endothelial function of arterialized vein graft in an experimental rat model?

BACKGROUND: This study aims to compare the effects of storage solutions commonly used in coronary artery bypass grafting on the vascular reactivity in vein graft interposed in arterial position in syngeneic rats. METHODS: Twenty-seven male Lewis rats were sacrified to sample a vein graft implanted 6 weeks ago into abdominal aorta position. The vein grafts were inferior venae cavae initially pretreated with heparinized saline solution (HS) or autologous heparinized blood (AHB) or our referent solution, GALA. The endothelial functionality, the in situ Reactive Oxygen Species (ROS) levels and the histological characteristics were conducted from segments of arterialized vein graft. RESULTS: At 6 weeks, graft thrombosis occurred respectively in 22% of AHB group, 62.5% in the HS group and 82.5% in the GALA group. In each group, significative intimal hyperplasia was observed. After 6 weeks, an endothelium-remodeling layer associated with an increase of wall thickness was observed in each group. Endothelium-dependent tone was reduced in the vein graft regardless of the group. No difference was observed concerning the ROS in vein graft between the different groups. In distal aortic sections, ROS levels were increased in HS and GALA groups. CONCLUSIONS: Storage solutions used in this experimental model of vein graft implanted in arterial position cause graft injury and a complete disappearance of vascular reactivity. GALA solution did not reduce intimal risk hyperplasia when the vein graft was exposed to arterial flow in a rat model.

A prospective, randomized, single-blind, multicentre, phase III study on organ preservation with Custodiol-N solution compared with Custodiol® solution in organ transplantation (kidney, liver and pancreas).

BACKGROUND: Organ preservation before transplantation is still a challenge. Both the University of Wisconsin and Bretschneider's histidine-tryptophan-ketoglutarate (HTK; Custodiol®) solution are standard for liver, kidney and pancreas preservation. Organ preservation with both solutions is comparable; recently, however, Custodiol® solution has been modified to Custodiol-N according to the needs of today. Thus, our study was defined to study its effect in clinical transplantation. METHODS: Patients undergoing kidney transplantation (n = 412) (including approximately 30 combined kidney-pancreas) or liver transplantation (n = 202) receive grafts that have been cold stored in either Custodiol® or Custodiol-N to demonstrate noninferiority of Custodiol-N regarding both graft function and graft injury after transplantation. DISCUSSION: Preclinical data have clearly shown that Custodiol-N is superior to Custodiol® in cold static organ preservation via mechanisms including inhibition of hypoxic cell injury, cold-induced cell injury and avoidance of adverse effects during warm exposure to the solution. Further clinical safety data on Custodiol-N for cardioplegia are available. Thus, this study was designed to compare Custodiol® with Custodiol-N for the first time in a prospective, randomized, single-blinded, multicentre, phase III clinical transplantation trial. TRIAL REGISTRATION: Eudra-CT, 2017-002198-20. Registered on 28 November 2018.

Fungal infection after keratoplasty and the role of antifungal supplementation to storage solution: a review.

Fungal infection after corneal transplantation is a rare, yet potentially devastating, postoperative complication and has become a growing concern for the transplant surgeon and eye banking community. The Eye Bank Association of America (EBAA) has reported an increasing trend in the rate of postkeratoplasty fungal infections and a reversal in the previously documented predominance of bacterial over fungal infections. Additionally, several studies have confirmed a high correlation between positive corneoscleral donor rim fungal cultures and postoperative infections. Optisol GS (Bausch & Lomb, Irvine, California, USA), the most extensively used corneal storage solution in US eye banks, does not currently contain any antifungal supplementation. Although large randomised control trials evaluating the efficacy and safety of routine antifungal supplementation to corneal storage solution are lacking, several investigative studies have assessed the role of antifungal agents in reducing fungal contamination of donor corneas without causing undue corneal toxicity. This review will present the current epidemiology of postkeratoplasty fungal infections and evidence for obtaining routine fungal rim cultures and antifungal supplementation of storage solution.

Efeito da infusão da solução M& G na proteção do tecido renal de ratos Wistar submetidos a isquemia e reperfusão programada / Effect of infusion of M& G solution for protection of renal tissue in Wistar rats subjected to programmed ischemia-reperfusion

Resumo Contexto A isquemia e reperfusão (I/R) renal está envolvida diretamente com insuficiência renal aguda, ocorrendo em casos como infarto por embolização ou trombose, quadros de septicemia e transplante renal. Esse processo é complexo, envolvendo respostas imunes inatas e adaptativas, presença de infiltrado celular, produção e liberação de citocinas e quimiocinas. Também desencadeia respostas celulares e liberação de espécies reativas de oxigênio, além de resultar em apoptose e, em alguns casos, necrose celular. Nesse contexto, é imprescindível a avaliação dos mecanismos de proteção ao tecido renal. Objetivos O objetivo foi testar a solução desenvolvida M&G, avaliando sua capacidade protetora no rim por meio de análise morfométrica e presença e expressão de citocinas inflamatórias (TNF-alfa, VEGF, HIF e IL-8). Métodos Foram selecionados 18 ratos Wistar, divididos em três grupos: Sham (S), Controle (C) e Estudo (E). O grupo S foi submetido ao processo cirúrgico sem o clampeamento arterial. No grupo C, foi clampeada a aorta acima e abaixo da artéria renal esquerda, sem a infusão de solução preservadora. No grupo E, além do clampeamento, realizou-se a punção da aorta e a infusão contínua da solução M&G por 20 minutos a 15 °C. Realizou-se a avaliação morfológica e imuno-histoquímica com os marcadores. Resultados Identificaram-se diferenças morfológicas entre o grupo S comparado aos grupos C e E. Na análise dos marcadores, houve redução na intensidade de expressão do TNF e na expressão do VEGF no grupo E. Não houve diferenças com HIF e IL-8 entre os grupos. Conclusões A solução M&G apresentou redução da presença e expressão de TNF-alfa e tendência de redução do VEGF.

Abstract Background Renal ischemia-reperfusion (I/R) is directly associated with acute renal failure and can occur in conditions such as infarction caused by embolization or thrombosis, septicemia, and kidney transplantation. The process is complex, involving innate and adaptive immune responses, presence of cellular infiltrate, and production and release of cytokines and chemokines. It also triggers cell responses and release of reactive oxygen species, in addition to causing apoptosis and, in some cases, cell necrosis. Against this background, evaluation of renal tissue protection mechanisms is essential. Objectives The objective of this study was to test the M&G solution, developed in prior research, evaluating its capacity to protect the kidneys using morphometric analysis and by assaying the presence and expression of inflammatory cytokines (TNF-alpha, VEGF, HIF, and IL-8). Methods Eighteen Wistar rats were divided into three groups: Sham (S), Control (C), and Experimental (E). The S group underwent the surgical operation, but without arterial clamping. In group C, the aorta was clamped above and below the left renal artery, without infusion of the preservation solution. In group E, in addition to clamping, the aorta was punctured and M&G solution was infused continuously for 20 minutes at 15o C. Morphological analysis and immunohistochemical assessment of markers were then conducted. Results Morphological differences were identified in group S compared with groups C and E. Analysis of markers revealed reduced intensity of expression of TNF and of VEGF in group E. There were no differences in HIF or IL-8 between groups. Conclusions The M&G solution was associated with a reduction in presence and expression of TNF-alpha and a trend to reduced VEGF.

Combating Donor Organ Shortage: Organ Care System Prolonging Organ Storage Time and Improving the Outcome of Heart Transplantations.

INTRODUCTION: Cardiovascular diseases are the number one cause of death globally contributing to 37% of all global deaths. A common complication of cardiovascular disease is heart failure, where, in such cases, the only solution would be to conduct a heart transplant. Every 10 minutes a new patient is added to the transplant waiting list. However, a shortage of human donors and the short window of time available to find a correct match and transplant the donors' heart to the recipient means that numerous challenges are faced by the patient even before the operation could be done, reducing their chances of living even further. METHODS: This review aims to evaluate the application of the Organ Care System (OCSTM) in improving the efficiency of heart storage based on journal articles obtained from PubMed, Elsevier Clinical Key, and Science Direct. RESULTS: Studies have shown that OCS is capable of extending the ischemic time 120 minutes longer than conventional methods without any detrimental effect on the recipient nor donor's safety. Based on the PROTECT I and PROCEED II study, 93% of transplantation recipients using the OCS system passed through the 30-day mortality period. DISCUSSION: OCS is able to prolong the ischemic time of donors' hearts by perfusing the organ at 34°C in a beating state, potentially reducing the detrimental effect of cold storage and providing additional assessment options. Another clear advantage is the implanting surgeon can assess the quality of the donor heart before surgery as well as providing a time safety buffer in unanticipated circumstances that will reduce the mortality risk of transplant recipients.

A novel endothelial damage inhibitor for the treatment of vascular conduits in coronary artery bypass grafting: protocol and rationale for the European, multicentre, prospective, observational DuraGraft registry.

BACKGROUND: Vein graft disease (VGD) impairs graft patency rates and long-term outcomes after coronary artery bypass grafting (CABG). DuraGraft is a novel endothelial-damage inhibitor developed to efficiently protect the structural and functional integrity of the vascular endothelium. The DuraGraft registry will evaluate the long-term clinical outcomes of DuraGraft in patients undergoing CABG procedures. METHODS: This ongoing multicentre, prospective observational registry will enrol 3000 patients undergoing an isolated CABG procedure or a combined procedure (ie, CABG plus valve surgery or other surgery) with at least one saphenous vein grafts or one free arterial graft (ie, radial artery or mammary artery). If a patient is enrolled, all free grafts (SVG and arterial will be treated with DuraGraft. Data on baseline, clinical, and angiographic characteristics as well as procedural and clinical events will be collected. The primary outcome measure is the occurrence of a major adverse cardiac event (MACE; defined as death, non-fatal myocardial-infarction, or need for repeat-revascularisation). Secondary outcome measures are the occurrence of major adverse cardiac and cerebrovascular events (MACCE; defined as death, non-fatal myocardial-infarction, repeat-revascularisation, or stroke), patient-reported quality of life, and health-economic data. Patient assessments will be performed during hospitalisation, at 1-month, 1-year, and annually thereafter to 5 years post-CABG. Events will be adjudicated by an independent clinical events committee. This European, multi-institutional registry will provide detailed insights into clinical outcome associated with DuraGraft. DISCUSSION: This European, multi-institutional registry will provide detailed insights into clinical outcome associated with the use of DuraGraft. Beyond that, and given the comprehensive data sets comprising of patient, procedural, and graft parameters that are being collected, the registry will enable for multiple subgroup analyses targeting focus groups or specific clinical questions. These may include analysis of subpopulations such as patients with diabetes or multimorbid high-risk patients (patient level), evaluation of relevance of harvesting technique including endoscopic versus open conduit harvesting (procedural level), or particular graft-specific aspects (conduit level). TRIAL REGISTRATION: ClinicalTrials.gov NCT02922088 . Registered October 3, 2016. ETHICS AND DISSEMINATION: The regional ethics committees have approved the registry. Results will be submitted for publication.

Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs.

Various methods have been devised to dissolve hydrogen gas in organ preservation solutions, including use of a hydrogen gas cylinder, electrolysis, or a hydrogen-generating agent. However, these methods require considerable time and effort for preparation. We investigated a practical technique for rapidly dissolving hydrogen gas in organ preservation solutions by using a canister containing hydrogen-absorbing alloy. The efficacy of hydrogen-containing organ preservation solution created by this method was tested in a miniature pig model of kidney transplantation from donors with circulatory arrest. The time required for dissolution of hydrogen gas was only 2-3 minutes. When hydrogen gas was infused into a bag containing cold ETK organ preservation solution at a pressure of 0.06 MPa and the bag was subsequently opened to the air, the dissolved hydrogen concentration remained at 1.0 mg/L or more for 4 hours. After warm ischemic injury was induced by circulatory arrest for 30 minutes, donor kidneys were harvested and perfused for 5 minutes with hydrogen-containing cold ETK solution or hydrogen-free cold ETK solution. The perfusion rate was faster from the initial stage with hydrogen-containing cold ETK solution than with hydrogen-free ETK solution. After storage of the kidney in hydrogen-free preservation solution for 1 hour before transplantation, no urine production was observed and blood flow was not detected in the transplanted kidney at sacrifice on postoperative day 6. In contrast, after storage in hydrogen-containing preservation solution for either 1 or 4 hours, urine was detected in the bladder and blood flow was confirmed in the transplanted kidney. This method of dissolving hydrogen gas in organ preservation solution is a practical technique for potentially converting damaged organs to transplantable organs that can be used safely in any clinical setting where organs are removed from donors.

Preservation Solutions for Kidney Transplantation: History, Advances and Mechanisms.

Solid organ transplantation was one of the greatest medical advances during the past few decades. Organ preservation solutions have been applied to diminish ischemic/hypoxic injury during cold storage and improve graft survival. In this article, we provide a general review of the history and advances of preservation solutions for kidney transplantation. Key components of commonly used solutions are listed, and effective supplementations for current available preservation solutions are discussed. At cellular and molecular levels, further insights were provided into the pathophysiological mechanisms of effective ingredients against ischemic/hypoxic renal injury during cold storage. We pay special attention to the cellular and molecular events during transplantation, including ATP depletion, acidosis, mitochondrial dysfunction, oxidative stress, inflammation, and other intracellular mechanisms.

The efficiency of heart protection with HTK or HTK-N depending on the type of ischemia.

We investigated isolated guinea pig hearts (n = 121) in an ischemia/ reperfusion model with the aim to compare the efficiency of the cardioplegic solution HTK with its novel replacement HTKN. Following consolidation with Tyrode's solution, ischemia started either immediately or after preceding cardioplegia with HTK, HTKN, or modified HTK enriched with Ca. Ischemia lasted either 80 min at 30 °C, or 360 min at 5 °C, or 81 min at 30 °C with intermittent cardioplegic perfusion. During ischemia we measured intracellular calcium (iCa++) and the time of gap junction uncoupling (t-in). During reperfusion we measured the reestablishment of cell coupling (t-ret), left ventricular developed pressure (LVDP), and heart rhythm (VC-RR). In 5 °C groups, iCa++ at t-in was significantly higher than before ischemia, and longest t-in, shortest t-ret, and best VC-RR were observed after HTK-protection. Of all 30 °C groups, the intermittent group with modified HTK showed shortest t-ret, best VC-RR, and the highest LVDP. At 5 °C, HTK groups had higher LVDP than HTK-N groups, but not at 30 °C. The data suggest that the higher calcium level in the HTK-N solution improves reperfusion after short ischemia at 30 °C but for long lasting ischemia at 5 °C it is beneficial to use the HTK solution.

The Effect of Histidine-tryptophan-ketoglutarate Solution and University of Wisconsin Solution: An Analysis of the Eurotransplant Registry.

BACKGROUND: Both University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are currently used in the Eurotransplant region for preservation of liver allografts. Previous studies on their effect have led to a lot of discussion. This study aims to compare the effect of HTK and UW on graft survival. METHODS: First liver transplantations in recipients 18 years or older from January 1, 2007, until December 31, 2016, were included. Graft survival was compared for livers preserved with HTK and UW at 30 days, 1, 3, and 5 years. Multivariable analysis of risk factors was performed and outcome was adjusted for important confounders. RESULTS: Of all 10 628 first liver transplantations, 8176 (77%) and 2452 (23%) were performed with livers preserved with HTK and UW, respectively. Kaplan-Meier curves showed significant differences in graft survival between HTK and UW at 30 days (89% vs 93%, P=<0.001), 1 year (75% vs 82%, P=<0.001), 3 years (67% vs 72%, P<0.001), and at 5 years (60% vs 67%, P<0.001). No significant differences in outcome were observed in separate analyses of Germany or non-German countries. In multivariable analysis, UW was associated with a decreased risk of graft loss at 30 days (HR 0.772, P=0.002) and at 1 year (0.847 (0.757-0.947). When adjusted for risk factors, no differences in long term outcome could be detected. CONCLUSIONS: Because the use of preservation fluids is clustered geographically, differences in outcome by preservation fluids are strongly affected by regional differences in donor and recipient characteristics. When adjusted for risk factors, no differences in graft survival exist between transplantations performed with livers preserved with either HTK or UW.

Organ Preservation in Liver Transplantation.

The discrepancy between the number of patients awaiting liver transplantation and the number of available donors has become a key issue in the transplant setting. Various strategies to cope with the donor shortage problem and to increase the use of suboptimal grafts have been explored. Machine perfusion has been applied ex situ to liver grafts in the effort to improve static cold-storage preservation. If a more extensive application of this technology confirms the preliminary results, machine perfusion will become crucial in increasing the donor pool as well as improving recipients' outcomes. In this review, the authors focused on the evolution of machine perfusion, from the first animal experiences to the latest evidence in humans, highlighting the pros and cons as well as the potential clinical applications of various types of machine.

Cold Storage Injury to Rat Small-bowel Transplants-Beneficial Effect of a Modified HTK Solution.

BACKGROUND: The small bowel is prone to ischemic injury during transport before transplantation, an injury that endangers the recipient patient. The small-bowel mucosal microcirculation in particular appears to be highly sensitive to injury. Current preservation solutions such as histidine-tryptophan-ketoglutarate (HTK) solution provide some protection to the graft. However, these were developed decades ago and do not address several critical processes, such as hypoxia-induced membrane pores and free radical-mediated hypothermic injury. METHODS: To protect the graft from cold ischemic injury, we implemented a modified HTK solution here, including glycine, alanine, and iron chelators in a heterotopic, syngeneic small-bowel transplantation model of the rat. The effects of the modified solution and its major components were compared against the conventional HTK solution using intravital microscopy in the early reperfusion period. RESULTS: The amino acid glycine, added to HTK solution, slightly improved mucosal perfusion. Both, the modified base solution (without iron chelators) and iron chelators increased functional capillary density of the mucosa during the early reperfusion period. The complete modified solution (with glycine, alanine, and iron chelators) significantly increased the perfusion index, functional capillary density of the mucosa, and red blood cell velocity in the grafts after reperfusion in comparison with the grafts preserved with HTK. CONCLUSIONS: The modified preservation solution improved the microcirculation of the transplants and needs detailed evaluation in further models of small-bowel transplantation.