Donation After Cardiac Death Liver Grafts Research Articles

Beneficial Effects of Combined Use of Extracorporeal Membrane Oxygenation and Hypothermic Machine Perfusion in Porcine Donors after Cardiac Death for Liver Transplantation.

Grafts from donors after cardiac death (DCD) have greatly contributed to expanding the donor organ pool. This study aimed to determine the benefits of subnormothermic extracorporeal membrane oxygenation (ECMO) and hypothermic machine perfusion (HMP) in a porcine model of DCD liver. Female domestic crossbred Large Yorkshire and Landrace pigs weighing approximately 20 kg were used. The abdominal aorta and inferior vena cava were cannulated and connected to an ECMO circuit for in situ perfusion of the abdominal organs at 22 °C for 60 min, 45 min after cardiac death. The pigs were divided into the cold storage (CS) group (n = 3), where liver grafts were preserved at 4 °C, and the HMP group (n = 3), where liver grafts were preserved by HMP at 8-10 °C. After 4 h of preservation, liver function was evaluated using an isolated liver reperfusion model for 2 h. Although the difference was insignificant, the liver effluent enzyme levels in the HMP group were lower than those in the CS group. Furthermore, morphological findings showed fewer injured hepatocytes in the HMP group than in the CS group. The combined use of in situ subnormothermic ECMO and HMP was beneficial for the functional improvement of DCD liver grafts.

Combined Use of Subnormothermic Extracorporeal Support and Hypothermic Oxygenated Machine Perfusion for Liver Graft After Cardiac Death in Pigs

The use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. This study aims to determine the benefits of extracorporeal membrane oxygenation (ECMO) and hypothermic oxygenated machine perfusion (HOPE) in a large animal model of DCD liver. After cardiac arrest, the abdominal aorta and the inferior vena cava were cannulated and connected to an ECMO circuit. Porcine livers were perfused in situ with ECMO at 22°C for 60 minutes after 45 minutes of cardiac death. Then, the livers were perfused for 4 hours by cold storage (CS) or HOPE. In group 1, non-in situ ECMO and grafts were preserved by HOPE. In group 2, in situ ECMO and grafts were preserved by HOPE. In group 3, in situ ECMO and grafts were preserved by CS. After preservation, all grafts were evaluated using an isolated reperfusion model (IRM) with autologous blood for 2 hours. During HOPE, aspartate aminotransferase (AST) levels and hepatic arterial pressure in group 2 tended to be lower than in group 1. Hematoxylin-eosin staining findings after HOPE showed more massive sinusoidal congestion and hepatocyte cytoplasmic vacuolization in group 1 than in group 2. The AST and LDH levels in group 2 at the start-up of IRM tended to be lower than in group 1. The combined use of in situ subnormothermic ECMO and HOPE is essential for the functional recovery of DCD liver grafts.

Effects of Short-Term Normothermic and Subnormothermic Perfusion After Cold Preservation on Liver Transplantation From Donors After Cardiac Death

BackgroundLiver transplantation from donors after cardiac death (DCD) could increase the pool of organs. We previously reported that oxygenated subnormothermic (20°C-25°C) ex vivo liver perfusion (SELP) improved the graft viability in rats. This study aimed to compare the effectiveness of SELP and normothermic (37°C) ex vivo liver perfusion (NELP) after cold storage (CS) in DCD liver grafts. MethodsMale Wistar rats were used, and grafts were retrieved 30 minutes after cardiac arrest. We performed oxygenated NELP and SELP with a Krebs-Henseleit buffer for different time points and durations: Group 0, donation performed from heart-beating donors (control); Group 1 (DCD group), donation performed from DCD donors with no treatments; Group 2, NELP performed before CS (30 minutes); Group 3, NELP performed after CS (30 minutes); Group 4, SELP performed after CS (30 minutes); Group 5, SELP performed after CS (60 minutes); and Group 6, SELP performed after CS (90 minutes). After 15 minutes of incubation at room temperature, the grafts were reperfused under normothermic conditions for 60 minutes as a model of liver transplantation. ResultsNo significant differences in body and liver weight were observed between all groups. In the SELP after CS groups, even 30 minutes of perfusion improved bile production, tumor necrosis factor-α, and interleukin-1β significantly compared with the DCD group (P < .05), comparable with NELP groups. ConclusionSELP rescued DCD livers from ischemia-reperfusion injury the same as the normothermic perfusion before or after CS groups. SELP after CS is more convenient than normothermic perfusion; hence, this technique may increase the organ pool.

Cytoprotective Effects of Mesenchymal Stem Cells During Liver Transplantation From Donors After Cardiac Death in Swine

BackgroundLiver transplantation from donors after cardiac death (DCDs) can increase the pool of available organs. Recently, mesenchymal stem cells (MSCs) have been used to treat various diseases. Some studies have reported that MSCs improve the outcome of liver transplantation from DCDs in mice. The aim of this study was to evaluate the cytoprotective effects and safety of MSC transplantation on liver grafts from DCDs in swine. MethodsFor the MSCs, we used swine adipose-derived stem cells (ADSCs). Landrace swine were divided into 3 groups (n = 5) as follows: 1. the heart-beating (HB) group, from which liver grafts were retrieved and transplanted; 2. the DCD group, from which liver grafts were retrieved 10 minutes after apnea-induced cardiac arrest and transplanted; and 3. the ADSC group, from which liver grafts were retrieved as with the DCD group, transplanted, and then infused with 1.0 × 107 ADSCs 2 hours after reperfusion. ResultsIn the HB group, all 5 recipients survived for >7 days, whereas all 5 recipients in the DCD group died within 24 hours after transplantation. In the ADSC group, 3 recipients survived for >7 days, whereas 2 recipients died within 4 days after transplantation. The survival rate was significantly higher in the ADSC group than in the DCD group. ConclusionsMSCs could protect the function of liver grafts from warm ischemia-reperfusion injury and improve the viability of DCD liver grafts.

Impact of human-derived hemoglobin based oxygen vesicles as a machine perfusion solution for liver donation after cardiac death in a pig model.

The recent clinical application of perfusion technology for the machine preservation of donation after cardiac death (DCD) grafts has some advantages. Oxygenation has been proposed for the preservation of DCD liver grafts. The aim of this study is to clarify whether the use of HbV-containing preservation solution during the subnormothermic machine perfusion (SNMP) of the liver graft improves the graft function of DCD porcine livers in an ex vivo reperfusion model. Pig livers were excised after 60 minutes of warm ischemic time and were preserved under one of three preservation conditions for 4 hours. The preservation conditions were as follows: 4°C cold storage (CS group; N = 5), Hypothermic machine preservation (HMP) with UW gluconate solution (HMP group; N = 5), SNMP (21°C) with UW gluconate solution (SNMP group; N = 5), SNMP (21°C) with HbVs (Hb; 1.8 mg/dl) perfusate (SNMP+HbV group; N = 5). Autologous blood perfusion was performed for 2 hours in an isolated liver reperfusion model (IRM). The oxygen consumption of the SNMP and SNMP+HbV group was higher than the HMP groups (p < 0.05). During the reperfusion, the AST level in the SNMP+HbV group was lower than that in the CS, HMP and SNMP groups. The changes in pH after reperfusion was significantly lower in SNMP+HbV group than CS and HMP groups. The ultrastructural findings indicated that the mitochondria of the SNMP+HbV group was well maintained in comparison to the CS, HMP and SNMP groups. The SNMP+HbVs preservation solution protected against metabolic acidosis and preserved the liver function after reperfusion injury in the DCD liver.

Effects of Subnormothermic Perfusion Before Transplantation for Liver Grafts from Donation After Cardiac Death: A Simplified Dripping Perfusion Method in Pigs

BackgroundLiver transplantation from donors after cardiac death (DCD) provides a solution to the donor shortage. However, DCD liver grafts are associated with a high incidence of primary graft nonfunction. We investigated the effectiveness of subnormothermic porcine liver perfusion, before transplantation from DCD, on graft viability. MethodsLandrace pigs (25–30 kg) were randomly allocated to 3 groups (5 per group): heart-beating (HB) graft, transplanted after a 4-hour period of cold storage (CS); DCD graft, retrieved 20 minutes after apnea-induced cardiac arrest (respiratory withdrawal) and transplanted after a 4-hour period of CS; and subnormothermic ex vivo liver perfusion (SELP) graft, retrieved in the same manner as the DCD graft but perfused with a subnormothermic oxygenated Krebs-Henseleit buffer (21–25°C, 10–15 cm H2O) for 30 minutes in a simplified dripping manner, without a machine perfusion system, after the 4-hour period of CS, and subsequently transplanted. ResultsAlthough all animals in the HB group survived for >7 days, all animals in the DCD group died within 12 hours after transplantation. In the SELP group, 2 recipients survived for >7 days and another 2 recipients were killed on day 5. The survival rate was significantly better for SELP than for DCD grafts (P = .0016). The values of tumor necrosis factor α were not significantly different between the SELP and HB groups. Preserved structure of the parenchyma was observed in the SELP group on histologic examination. ConclusionsA simplified subnormothermic perfusion before liver transplantation is expected to improve graft viability and survival.

Cytoprotective Effects of Mesenchymal Stem Cells During Liver Transplantation from Donors After Cardiac Death in Rats

BackgroundLiver transplantation from donors after cardiac death (DCD) might increase the pool of available organs. Recently, some investigators reported the potential use of mesenchymal stem cells (MSCs) to improve the outcome of liver transplantation from DCD. The aim of this study was to evaluate the cytoprotective effects and safety of MSC transplantation on liver grafts from DCD. MethodsRats were divided into 4 groups (n = 5) as follows: 1. the heart-beating group, in which liver grafts were retrieved from heart-beating donors; 2. the DCD group, in which liver grafts were retrieved from DCD that had experienced apnea-induced agonal conditions; 3. the MSC-1 group, and 4. the MSC-2 group, in which liver grafts were retrieved as with the DCD group, but were infused MSCs (2.0 × 105 or 1.0 × 106, respectively). The retrieved livers were perfused with oxygenated Krebs-Henseleit bicarbonate buffer (37°C) through the portal vein for 2 hours after 6 hours of cold preservation. Perfusate, bile, and liver tissues were then investigated. ResultsBile production in the MSC-2 group was significantly improved compared with that in the DCD group. Based on histologic findings, narrowing of the sinusoidal space in the both MSC groups was improved compared with that in the DCD group. ConclusionsMSCs could protect the function of liver grafts from warm ischemia-reperfusion injury and improve the viability of DCD liver grafts. In addition, we found that the infusion of 1.0 × 106 MSCs does not obstruct the hepatic sinusoids of grafts from DCD.

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.

Mesenchymal stem cells improve mouse non-heart-beating liver graft survival by inhibiting Kupffer cell apoptosis via TLR4-ERK1/2-Fas/FasL-caspase3 pathway regulation.

BackgroundLiver transplantation is the optimal treatment option for end-stage liver disease, but organ shortages dramatically restrict its application. Donation after cardiac death (DCD) is an alternative approach that may expand the donor pool, but it faces challenges such as graft dysfunction, early graft loss, and cholangiopathy. Moreover, DCD liver grafts are no longer eligible for transplantation after their warm ischaemic time exceeds 30 min. Mesenchymal stem cells (MSCs) have been proposed as a promising therapy for treatment of certain liver diseases, but the role of MSCs in DCD liver graft function remains elusive.MethodsIn this study, we established an arterialized mouse non-heart-beating (NHB) liver transplantation model, and compared survival rates, cytokine and chemokine expression, histology, and the results of in vitro co-culture experiments in animals with or without MSC infusion.ResultsMSCs markedly ameliorated NHB liver graft injury and improved survival post-transplantation. Additionally, MSCs suppressed Kupffer cell apoptosis, Th1/Th17 immune responses, chemokine expression, and inflammatory cell infiltration. In vitro, PGE2 secreted by MSCs inhibited Kupffer cell apoptosis via TLR4-ERK1/2-caspase3 pathway regulation.ConclusionOur study uncovers a protective role for MSCs and elucidates the underlying immunomodulatory mechanism in an NHB liver transplantation model. Our results suggest that MSCs are uniquely positioned for use in future clinical studies owing to their ability to protect DCD liver grafts, particularly in patients for whom DCD organs are not an option according to current criteria.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0416-y) contains supplementary material, which is available to authorized users.

Subnormothermic Machine Perfusion Preservation With Rewarming for Donation After Cardiac Death Liver Grafts in Pigs

BackgroundThe use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, the implementation of such a strategy requires the development of novel preservation methods to recover from changes owing to warm ischemia. The aim of this study was to evaluate the effectiveness of subnormothermic machine perfusion (MP) preservation with rewarming for porcine DCD liver grafts for transplantation. MethodsPorcine livers were perfused with newly developed MP system. The livers were perfused for 4 hours with modified University of Wisconsin gluconate solution. Group 1 grafts were preserved with no warm ischemia time (WIT) and hypothermic MP (HMP) for 4 hours. Group 2 grafts were preserved with WIT 60 minutes and HMP for 4 hours. Group 3 grafts were preserved with WIT 60 minutes and rewarming up to 25°C by MP (RMP) for 4 hours. ResultsThe aspartate aminotransferase and lactate dehydrogenase in the effluent maintained at lower level in group 3 compared with group 2. However, tissue ATP levels did not recover in groups 2 and 3. Histologically, the fatty degenerate and swelling of the hepatocyte was slightly seen in all groups. The normal structure of the hepatocellular cords, the bile duct and the sinusoid endothelium were preserved in all groups. ConclusionsPotentially, subnormothermic preservation with rewarming is expected to help the recovery of function for DCD liver grafts.

Applicability of Combined Use of Extracorporeal Support and Temperature-Controlled Machine Perfusion Preservation for Liver Procurement of Donors After Cardiac Death in Pigs

BackgroundThe use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. The objective of this study is to determine the benefits of extracorporeal membrane oxygenation (ECMO) and subnormothermic machine perfusion (MP) with rewarming in a large animal model of DCD liver. MethodsAfter cardiac arrest, the abdominal aorta and the inferior vena cava were cannulated and connected to an ECMO circuit. Porcine livers were perfused in situ with ECMO at 22°C for 60 minutes after 60 minutes of cardiac death. Then the livers were perfused for 4 hours by MP as a graft viability test. In group 1, non–in situ ECMO and grafts were preserved hypothermic MP. In group 2, non–in situ ECMO and grafts were preserved subnormothermic rewarming MP. In group 3, we used ECMO and subnormothermic rewarming MP. To assess potential methods and effect, effluent enzymes were measured. Portal vein and hepatic artery pressure during MP were evaluated. ResultsEffluent enzyme of AST, alanine aminotransferase and LDH as viability markers were significantly low (aspartate aminotransferase, 2899, 2292, and 972 IU/L; alanine aminotransferase, 134, 140, and 72 IU/L; and lactate dehydrogenase, 4354, 4455, and 1855 IU/L in each group, respectively). Portal vein and hepatic artery pressure during preservation came down smoothly in group 3 compared with group 1. ConclusionsThe combined use of in situ subnormothermic ECMO and machine preservation with rewarming is more essential for the recovery and resuscitating function of DCD liver grafts.

Potential approaches to improve the outcomes of donation after cardiac death liver grafts.

There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death (DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications. In order to maximize the usage of DCD livers several new preservation approaches have been proposed. Here, we will review 3 innovative organ preservation methods: (1) different ex vivo perfusion techniques; (2) persufflation with oxygen; and (3) addition of thrombolytic therapy. Improvement of the quality of DCD liver grafts could increase the pool of liver graft's for transplantation, improve the outcomes, and decrease the mortality on the waiting list.

First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis.

Exposure of donor liver grafts to prolonged periods of warm ischemia before procurement causes injuries including intrahepatic cholangiopathy, which may lead to graft loss. Due to unavoidable prolonged ischemic time before procurement in donation after cardiac death (DCD) donation in 1 participating center, each liver graft of this center was pretreated with the new machine perfusion "Hypothermic Oxygenated PErfusion" (HOPE) in an attempt to improve graft quality before implantation. HOPE-treated DCD livers (n = 25) were matched and compared with normally preserved (static cold preservation) DCD liver grafts (n = 50) from 2 well-established European programs. Criteria for matching included duration of warm ischemia and key confounders summarized in the balance of risk score. In a second step, perfused and unperfused DCD livers were compared with liver grafts from standard brain dead donors (n = 50), also matched to the balance of risk score, serving as baseline controls. HOPE treatment of DCD livers significantly decreased graft injury compared with matched cold-stored DCD livers regarding peak alanine-aminotransferase (1239 vs 2065 U/L, P = 0.02), intrahepatic cholangiopathy (0% vs 22%, P = 0.015), biliary complications (20% vs 46%, P = 0.042), and 1-year graft survival (90% vs 69%, P = 0.035). No graft failure due to intrahepatic cholangiopathy or nonfunction occurred in HOPE-treated livers, whereas 18% of unperfused DCD livers needed retransplantation. In addition, HOPE-perfused DCD livers achieved similar results as control donation after brain death livers in all investigated endpoints. HOPE seems to offer important benefits in preserving higher-risk DCD liver grafts.

Donation after cardiac death liver transplantation: Graft quality evaluation based on pretransplant liver biopsy.

Donation after cardiac death (DCD) liver grafts are associated with inferior clinical outcomes and high discard rates because of poor graft quality. We investigated the predictive value of DCD liver biopsy for the pretransplant graft quality evaluation. DCD liver transplants that took place between October 2010 and April 2014 were included (n = 127). Histological features of graft biopsy samples were analyzed to assess risk factors for graft survival. Macrovesicular steatosis ≥ 20% [hazard ratio (HR) = 2.973; P = 0.045] and sinusoidal neutrophilic infiltrate (HR = 6.969; P = 0.005) were confirmed as independent risk factors for graft survival; hepatocellular swelling, vacuolation, and necrosis failed to show prognostic value. Additionally, a donor serum total bilirubin level ≥ 34.2 μmol/L was also associated with a lower probability of graft survival. Our analysis indicates that macrovesicular steatosis ≥ 20% and sinusoidal neutrophilic infiltrate are novel and useful histological markers for DCD liver grafts with unacceptable quality. This finding can be used by transplant surgeons to improve DCD liver acceptance protocols.

The bile duct in donation after cardiac death donor liver transplant.

This review considers the biliary complications associated with liver transplantation using donation after cardiac death (DCD) donor grafts. The increasing use of DCD liver grafts with their increased incidence of biliary complications is discussed. The ethics of this greater use is briefly analysed. Recent animal and human study evidence to support the peribiliary vascular plexus' role in ischaemic cholangiopathy is reviewed. Recent advances in in-vivo and ex-vivo perfusion are explored. In particular, the latest theories regarding perfusion's peribiliary plexus preserving effects and the mechanism by which biliary regeneration may be promoted as a consequence are discussed. This article explores the need for DCD liver graft use and the associated biliary complications. The current theories regarding the cause of DCD biliary complications are reviewed, as are the current strategies to reduce them.

Impact of Machine Perfusion Preservation of Liver Grafts From Donation After Cardiac Death

Because of the critical shortage of deceased donor grafts, using a donation after cardiac death (DCD) donor is an important resource. However, the ischemic damage of those DCD grafts jeopardizes organ viability during cold storage. Maintaining organ viability after donation until transplantation is important for optimal graft function and survival. This review describes the effective preservation in transplantation for DCD livers. Concepts and development of machine perfusion for DCD liver grafts to reduce ischemia/reperfusion injury are discussed. Despite the fact that hypothermic machine perfusion might be superior to static cold preservation, DCD livers are exposed to hypothermia-induced damage. Recently, some groups introduced the beneficial effects of normothermic or subnormothermic machine perfusion in DCD liver preservation and transplantation.

Rewarming Preservation by Organ Perfusion System for Donation After Cardiac Death Liver Grafts in Pigs

BackgroundUse of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, this requires the development of novel preservation methods to recover the organ from changes due to warm ischemia time (WIT). MethodsPorcine livers were perfused with a newly developed machine perfusion (MP) system. The livers were perfused with modified University of Wisconsin solution (UW) − gluconate. All grafts were procured after acute hemorrhagic shock with the ventilator off. For group 1 (n = 6), grafts were procured after WIT of 60 minutes and preserved by hypothermic MP (HMP) for 3 hours. For group 2 (n = 5), grafts were preserved with 2 hours of simple cold storage (SCS) and HMP for 2 hours. For group 3 (n = 6), grafts were preserved with 2 hours of SCS and rewarming up to 25°C by MP for 2 hours (RMP). The preserved liver grafts were transplanted orthotopically. ResultsThe alanine aminotransferase level in perfusate in RMP during perfusion preservation was maintained at less than that of HMP. The levels of aspartate aminotransferase and lactate dehydrogenase in the 2 hours after reperfusion were significantly lower in group 3. Histologically, the necrosis of hepatocytes was less severe in group 3. The survival rate in group 3 was 2/4, but 0/4 in the other group. ConclusionRMP is expected to facilitate the recovery of the DCD liver grafts.

Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model

BackgroundEffects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. Materials and methodsDCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. ResultsSignificant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. ConclusionHypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.

Normothermic Acellular Ex Vivo Liver Perfusion (NEVLP) Reduces Liver and Bile Duct in DCD Liver Grafts

It is important to develop a large animal model that closely resembles ischemic type biliary stricture (ITBS) in donation after cardiac death (DCD) grafts. The studies by Brunner et al (3) and Hansen et al (4) investigated common bile duct biopsies in humans after cold storage and reperfusion. In both studies, the biopsies were taken from the most distal part of the common bile duct, which is usually not used for the anastomosis.

Impact of Rewarming Preservation by Continuous Machine Perfusion: Improved Post-Transplant Recovery in Pigs

BackgroundUtilization of grafts from donors after cardiac death (DCD) greatly expands the organ pool. However, implementation of such a strategy requires the development of novel preservation methods to achieve recovery from changes owing to warm ischemia. MethodsTo assess potential methods, porcine livers harvested after 60 minutes of warm ischemic time (WIT) were perfused and preserved under the following conditions: Group 1 (n = 3), 2-hour simple cold storage and 2-hour machine perfusion (MP) at 8°C; group 2 (n = 3), 2 hours at 25°C and MP at 25°C and group 3 (n = 3), 2-hour simple cold storage and gradual rewarming to 25°C by MP. The preserved liver grafts were transplanted orthotopically into recipients. ResultsThe aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and hyaluronic acid (HA) levels in recipient blood at 2 hours after reperfusion were significantly lower among group 3: AST, 789 ± 258.8, 1203 ± 217.0, and 421 ± 55.8 IU/L; LDH, 1417 ± 671.2, 2132 ± 483.9, and 634 ± 263.9 IU/L; and HA, 1660 ± 556.5, 1463 ± 332.3, and 575 ± 239.0 ng/mL for groups 1, 2 and 3, respectively. Histologically, necrosis and swelling of hepatocytes were less severe among group 3 than groups 1 and 2. Group 3 animals showed better vital responses and started spontaneous breathing within 2 hours after reperfusion; 1 recipient survived for >24 hours, although all animals in groups 1 and 2 died within 2 to 3 hours after reperfusion. ConclusionRewarming by MP preservation may facilitate recovery and resuscitation of DCD liver grafts.