Ethical issues of organ donation after circulatory death: Considerations for a successful implementation in Chile.

Organ transplantation is a lifesaving procedure for end-organ damage and remains up to today as the most cost-effective alternative to treat these conditions. However, the main limitation to performing organ transplants is the availability of donor organs suitable for transplantation. To increase the donor pool, expanding organ donation from the conventional neurologic determination of death (NDD) to include circulatory determination of death (DCD) has been a well-established method of increasing donors in other countries. In this article, we discuss the clinical and ethical considerations for introducing DCD in Chile. The concepts we have used could very well be translatable to other similar countries which have not implemented this donation system yet. The most relevant issue to date is that DCD needs to alter the care of dying patients to obtain quality donor organs. In some countries, including Chile, there are some cultural barriers regarding withdrawal-of-care. These barriers include confusing withdrawal of care with acceleration of death, which leads to many practitioners refusing to remove artificial life support, and in turn only minimize ventilatory support or switch to a T-tube (without extubation). This cultural barrier could be overcome with careful consideration of the opinions of healthcare workers, family members, community and policy-based stakeholders. We also identified ethical issues related to informed consent of both donor and recipients, among other relevant ethical considerations. In conclusion, DCD donation in Chile can increase organ donation numbers in one of Latin America's countries with the lowest effective donor rate. However, this opportunity must be taken with caution to avoid the opposite effect if this policy is not well implemented, respecting the sound ethical principles mentioned in this paper.

Machine perfusion of circulatory determined death hearts: A scoping review.

BACKGROUND: Ex vivo machine perfusion (EVMP) is reported to can successfully be applied for donor heart preservation. To respond to the organ shortage, some centres also accept hearts from marginal donors such as non-heart beating donors (NHBD) or hearts donated after cardiac death (DCD) for heart transplantation (HTx). Clinical as well as preclinical science on EVMP of DCD hearts seems to be promising but the ideal perfusion practice itself appears unclear. OBJECTIVES: In accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA), this systematic review scopes all EVMP techniques for human and animal DCD heart preservation and addresses three specific questions, which refer to (a) the perfusion solutions, (b) the perfusion parameters and respective target values and (c) if possible, a direct comparison between cold static storage (CSS) and EVMP. RESULTS: Search results predominantly consisted of animal studies. Either perfusion with a crystalloid or blood-based solution, each with cardioplegic or non-cardioplegic properties was used. Some perfusates were supplemented with specific pharmacological medication to block pathophysiological pathways, which are involved in ischemia/reperfusion injury or edema formation. Besides normothermic EVMP with oxygenated blood, a wide range of temperature was applied in all approaches, with the lowest temperature at 4 °C. Pressure controlled anterograde Langendorff perfusion was applied mostly. If investigated, crystalloid machine perfusion was presented superior to CSS. CONCLUSIONS: Only blood based EVMP was introduced into clinical practice. More research, clinical as well as preclinical, is needed to develop the ideal EVMP technique, in terms of blood or crystalloid perfusion.

Current situation of clinical islet transplantation from allogeneic toward xenogeneic.

Currently, type 1 diabetes requires lifelong insulin injection and careful blood glucose control to prevent secondary complications, but islet transplantation could make a type 1 diabetic patient insulin independent. On the other hand, islet transplantation needs human donors and donor shortage is the most serious issue. To alleviate the donor shortage, non-heart-beating and living donors were used; in addition, the efficacy of islet isolation and transplantation has been improved. However, the donor shortage issue will not be solved as long as human donors are the only source. To solve the donor shortage issue, islet xenotransplantation using porcine islets was initiated in 1994. Islet xenotransplantation has a potential to cure many type 1 diabetic patients, although there is the risk of developing serious or novel infection. Therefore, the World Health Organization has been interested in xenotransplantation, and the International Xenotransplantation Association (IXA) has published consensus statements to initiate xenogeneic islet transplantation. Clinical islet xenotransplantation was conducted under the official regulation, and safety and efficacy data have been accumulated. Currently an efficient method to overcome xenorejection is an important research target. In addition to traditional immunosuppressive drugs and immune isolation methods, the gene modification with CRISPR and blastocyst complementation have been investigated with promising outcomes. Once the xenorejection issue is overcome, islet xenotransplantation should become a curative treatment for type 1 diabetic patients.

The Effects of Using Pancreases Obtained from Brain-Dead Donors for Clinical Islet Transplantation in Japan.

BACKGROUND: The pool of brain-dead donors (BDDs) was increased with the revision to the relevant law in 2010, and islet transplantation from BDDs was started in 2013. The present study assessed the influence of using pancreases from BDDs on islet transplantation in Japan. METHODS: The donor information registered with the secretariat of islet transplants from 2012 was reviewed, and the results of 86 clinical islet isolations performed in Japan between 2003 and 2018 with non-heart-beating donors (NHBDs) (n = 71) and BDDs (n = 15) were investigated. RESULTS: The number of cases for which donor information was registered with the secretariat of islet transplants increased to 1.84 cases/month from 2013 to 2018 in comparison to 1.44/month in 2012, when only NHBDs were used. The median pancreatic islet yield was 275,550 IEQ (Islet equivalents) in the NHBD group but 3,627,000 in the BDD group, which amounted to a statistically significant difference (p = 0.02). As a result, 38/71 cases (53.5%) were achieved successful islet isolation (>5000 IEQ per recipient weight (kg)) was achieved in 38/71 cases (53.5%) in the NHBD group, and 12/15 cases (80.0%) in the BDD group; thus, the rate of successful islet transplantation was higher in the BDD group. CONCLUSION: The use of pancreases from BDDs has increased the overall number of cases for which donor information is registered with the secretariat of islet transplants and has improved the performance of islet isolation, thereby increasing the probability of successfully achieving islet transplantation.

The Airflow Characteristics in a 3D Airway Model Based on CT Images / 医用生物力学

Objective To discuss the mass transfer of low temperature gas in the lung bronchus, so as to provide a theoretical basis for the implementation of hypothermic ventilation cooling non-heart-beating donor (NHBD) lung program. Methods A real airway model was reconstructed based on human lung CT images, and the computational fluid dynamics (CFD) method was used to investigate the airflow characteristics inside the airway during reciprocating ventilation. The effect of ventilation frequency (0.5, 0.25, 0.125 Hz) on bronchial flow was also studied. Results The flow in the airway showed complex three-dimensional （3D） flow characteristics during reciprocating ventilation. The flow in different areas of the airway was different during inhaling and exhaling; the irregular bronchial geometry had an important effect on its internal flow; when the ventilation frequency decreased from 0.5 Hz to 0.125 Hz, the thickness of flow boundary layer would increase, and the mainstream velocity in different areas of the airway was enhanced to different degrees. Conclusions The real airway model based on CT 3D reconstruction was more accurate than the ideal circularity tube model in showing the bronchial flow. The research findings have an important guiding significance to optimize the hypothermic ventilation cooling NHBD lung technique.

Stereological assessment of the blood-air barrier and the surfactant system after mesenchymal stem cell pretreatment in a porcine non-heart-beating donor model for lung transplantation.

More frequent utilization of non-heart-beating donor (NHBD) organs for lung transplantation has the potential to relieve the shortage of donor organs. In particular with respect to uncontrolled NHBD, concerns exist regarding the risk of ischaemia/reperfusion (IR) injury-related graft damage or dysfunction. Due to their immunomodulating and tissue-remodelling properties, bone-marrow-derived mesenchymal stem cells (MSCs) have been suspected of playing a beneficial role regarding short- and long-term survival and function of the allograft. Thus, MSC administration might represent a promising pretreatment strategy for NHBD organs. To study the initial effects of warm ischaemia and MSC application, a large animal lung transplantation model was generated, and the structural organ composition of the transplanted lungs was analysed stereologically with particular respect to the blood-gas barrier and the surfactant system. In this study, porcine lungs (n = 5/group) were analysed. Group 1 was the sham-operated control group. In pigs of groups 2-4, cardiac arrest was induced, followed by a period of 3 h of ventilated ischaemia at room temperature. In groups 3 and 4, 50 × 106 MSCs were administered intravascularly via the pulmonary artery and endobronchially, respectively, during the last 10 min of ischaemia. The left lungs were transplanted, followed by a reperfusion period of 4 h. Then, lungs were perfusion-fixed and processed for light and electron microscopy. Samples were analysed stereologically for IR injury-related structural parameters, including volume densities and absolute volumes of parenchyma components, alveolar septum components, intra-alveolar oedema, and the intracellular and intra-alveolar surfactant pool. Additionally, the volume-weighted mean volume of lamellar bodies (lbs) and their profile size distribution were determined. Three hours of ventilated warm ischaemia was tolerated without eliciting histological or ultrastructural signs of IR injury, as revealed by qualitative and quantitative assessment. However, warm ischaemia influenced the surfactant system. The volume-weighted mean volume of lbs was reduced significantly (P = 0.024) in groups subjected to ischaemia (group medians of groups 2-4: 0.180-0.373 µm³) compared with the sham control group (median 0.814 µm³). This was due to a lower number of large lb profiles (size classes 5-15). In contrast, the intra-alveolar surfactant system was not altered significantly. No significant differences were encountered comparing ischaemia alone (group 2) or ischaemia plus application of MSCs (groups 3 and 4) in this short-term model.

Clinical outcomes of donation after circulatory death liver transplantation in primary sclerosing cholangitis.

BACKGROUND & AIM: Primary sclerosing cholangitis (PSC) is a progressive fibro-inflammatory cholangiopathy for which liver transplantation is the only life-extending intervention. These patients may benefit from accepting liver donation after circulatory death (DCD), however their subsequent outcome is unknown. The aim of this study was to determine the clinical impact of using DCD liver grafts in patients specifically undergoing transplantation for PSC. METHODS: Clinical outcomes were prospectively evaluated in PSC patients undergoing transplantation from 2006 to 2016 stratified by donor type (DCD, n=35 vs. donation after brainstem death [DBD], n=108). RESULTS: In liver transplantation for PSC; operating time, days requiring critical care support, total ventilator days, incidence of acute kidney injury, need for renal replacement therapy (RRT) or total days requiring RRT were not significantly different between DCD vs. DBD recipients. Although the incidence of ischaemic-type biliary lesions was greater in the DCD group (incidence rate [IR]: 4.4 vs. 0 cases/100-patient-years; p<0.001) there was no increased risk of post-transplant biliary strictures overall (hazard ratio [HR]: 1.20, 0.58-2.46; p=0.624), or in sub-analysis specific to anastomotic strictures or recurrent PSC, between donor types. Graft loss and mortality rates were not significantly different following transplantation with DCD vs. DBD livers (IR: 3.6 vs. 3.1 cases/100-patient-years, p=0.34; and 3.9 vs. 4.7, p=0.6; respectively). DCD liver transplantation in PSC did not impart a heightened risk of graft loss (HR: 1.69, 0.58-4.95, p=0.341) or patient mortality (0.75, 0.25-2.21, p=0.598). CONCLUSION: Transplantation with DCD (vs. DBD) livers in PSC patients does not impact graft loss or patient survival. In an era of organ shortage, DCD grafts represent a viable therapeutic option for liver transplantation in PSC patients. Lay summary: This study examines the impact of liver transplantation in primary sclerosing cholangitis (PSC) with organs donated after circulatory death (DCD), compared to donation after brainstem death (DBD). We show that in appropriately selected patients, the outcomes for DCD transplantation mirror those using DBD livers, with no significant differences in complication rate, patient survival or transplanted liver survival. In an era of organ shortage and increasing wait-list times, DCD livers represent a potential treatment option for transplantation in PSC.

Retrograde Oxygen Persufflation of Kidney - Experiment on an Animal.

AIM: There is still a lack of organs for transplantation purposes. In the field of kidney and liver transplantation, one available solution is the use of organs from so-called marginal donors. These donors can be e.g. non-heart-beating donors. In these cases, perfusion and preservation of organs intended for transplantation is generally more difficult. Retrograde oxygen persufflation (ROP) may be a possible solution to this issue. This method is based on retrograde perfusion by oxygen through the renal vein thus reconditioning the organ. MATERIALS AND METHODS: We operated on 10 animals (porcine models). Ischemic injury of the right kidney was simulated in all animals. In group A (N=5), kidneys were perfused with retrograde oxygen persufflation after explantation. In group B (N=5), kidneys were perfused intrarterially as in usual clinical practice. After perfusion all kidneys were transplanted to the original donor animal. Quality of graft restitution was evaluated by the urea level obtained from the renal vein and by histopathological analysis after explantation. RESULTS: We found no statistically significant differences between groups A and B in urea levels after transplantation, nor did we find any significant differences in quality of kidney parenchyma restoration between these groups. CONCLUSION: Retrograde oxygen persufflation is able to protect and restore kidney parenchyma.

Unusual case of tacrolimus vascular toxicity after deceased donor renal transplantation.

We report a case of tacrolimus vascular toxicity found on a protocol biopsy shortly after a deceased donor renal transplantation. The patient was immunologically high-risk and acute antibody-mediated rejection during post-transplant dialysis phase was suspected on the protocol biopsy. Although the patient was stable after treatment of rejection, a further examination showed a very rare but specific side-effect of tacrolimus. It is sometimes difficult to make a differential diagnosis during postoperative dialysis period among AMR, primary non-functioning, drug toxicity, infection or just prolonged recovery from the damage of a long agonal phase on the non-heart beating donor. Although the possibilities of coexistence of rejection or other causes such as infection have not been completely excluded, it is important to be aware of this unusual side effect of tacrolimus.

Controlled non-heart beating donor lung transplantation: initial experience in Spain.

Although the number of lung transplants in Spain is increasing annually, more organs are required to ease waiting lists. Controlled non-heart beating donors (NHBD) (Maastricht III) are a reality at international level, and contribute significantly to increasing donor numbers. In this study, we present our NHBD protocol and the initial experience in Spain using lung grafts from this type of donor. Three bilateral lung transplants were performed between January 2012 and December 2014. Preservation was by ex-vivo lung perfusion in 2 cases and by traditional cold ischemia in the other. None of the patients developed grade 3 primary graft dysfunction, no in-hospital mortality was recorded and 1-year survival was 100%. These initial results, and international experience, should help to develop similar protocols to encourage the use of controlled non-heart beating donors.

Lung transplantation from donation after cardiocirculatory death: a systematic review and meta-analysis.

BACKGROUND: Lung transplantation (LTx) can extend life expectancy and enhance the quality of life for select patients with end-stage lung disease. In the setting of donor lung shortage and waiting list mortality, the interest in donation after cardiocirculatory death (DCD) is increasing. We performed a systematic review and meta-analysis to compare outcomes between DCD and conventional donation after brain death (DBD). METHODS: PubMed, CINAHL, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and ClinicalTrials.gov were searched. We identified original research studies with 1-year post-transplant survival data involving >5 DCD transplants. We performed meta-analyses examining 1-year survival, primary graft dysfunction, and acute rejection after LTx. RESULTS: We identified 519 citations; 11 observational cohort studies met our inclusion criteria for systematic review, and 6 met our inclusion criteria for meta-analysis. There were no differences found in 1-year mortality after LTx between DCD and DBD cohorts in individual studies or in the meta-analysis (DCD [n = 271] vs DBD [n = 2,369], relative risk [RR] 0.88, 95% confidence interval [CI] 0.59-1.31, p = 0.52, I(2) = 0%). There was also no difference between DCD and DBD in a pooled analysis of 5 studies reporting on primary graft dysfunction (RR 1.09, 95% CI 0.68-1.73, p = 0.7, I(2) = 0%) and 4 studies reporting on acute rejection (RR 0.72, 95% CI 0.49-1.05, p = 0.09, I(2) = 0%). CONCLUSIONS: Survival after LTx from DCD is comparable to survival after LTx from DBD in observational cohort studies. DCD appears to be a safe and effective method to expand the donor pool.

Experience of a Maastrich type II non heart beating donor program in a small city: preliminary results.

OBJECTIVE: To study the results of a non-controlled cardiac death (Maastricht type II) donor program in a city of 200,000 inhabitants. The study was initially focused on lung donation and was extended to kidney donation after 9 months. DESIGN: A prospective observational study was conducted between October 2012 and December 2013. SETTING: The Intensive Care Unit of Marqués de Valdecilla University Hospital in Santander (Spain), and surrounding areas. POPULATIONS: Patients (< 55 years) who died of out-of-hospital cardiac arrest. INTERVENTIONS: All out-of-hospital cardiac arrests were treated with mechanical cardiac compression (LUCAS II). The diagnosis of death and organ preservation were performed in the ICU. RESULTS: A total of 14 calls were received, of which three were discarded. Of the 11 potential donors, 7 were effective donors with a median age of 39.5 years (range: 32-48). A total of 5 single lung transplants and four kidney transplants were performed. In addition, corneas and tissues were harvested. The non-valid donors were rejected mainly due to technical problems. There were no donation refusals on the part of the patient relatives. The lung transplant patient survival rate was 100% after one month and 80% after one year. One month after transplantation, the kidney recipients had a serum creatinine concentration of<2mg/dl. The interval from cardiac arrest to renal preservation was 80minutes (range: 71-89), and the interval from cardiac arrest to lung preservation was 84minutes (range: 77-94). CONCLUSIONS: A Maastricht type II donation program in a small city is viable for both abdominal and thoracic organs. The program was initially very cautious, but its potential is easily improvable by increasing donor and by equipping mobile ICU ambulances with mechanical cardiac compression systems. Full management of the donor in the ICU, avoiding the emergency department or operating rooms, reduces the warm ischemia time, thereby improving transplant outcomes.

Effects of exogenous surfactant on the non-heart-beating donor lung graft in experimental lung transplantation - a stereological study.

The use of non-heart-beating donor (NHBD) lungs may help to overcome the shortage of lung grafts in clinical lung transplantation, but warm ischaemia and ischaemia/reperfusion injury (I/R injury) resulting in primary graft dysfunction represent a considerable threat. Thus, better strategies for optimized preservation of lung grafts are urgently needed. Surfactant dysfunction has been shown to contribute to I/R injury, and surfactant replacement therapy is effective in enhancing lung function and structural integrity in related rat models. In the present study we hypothesize that surfactant replacement therapy reduces oedema formation in a pig model of NHBD lung transplantation. Oedema formation was quantified with (SF) and without (non-SF) surfactant replacement therapy in interstitial and alveolar compartments by means of design-based stereology in NHBD lungs 7 h after cardiac arrest, reperfusion and transplantation. A sham-operated group served as control. In both NHBD groups, nearly all animals died within the first hours after transplantation due to right heart failure. Both SF and non-SF developed an interstitial oedema of similar degree, as shown by an increase in septal wall volume and arithmetic mean thickness as well as an increase in the volume of peribron-chovascular connective tissue. Regarding intra-alveolar oedema, no statistically significant difference could be found between SF and non-SF. In conclusion, surfactant replacement therapy cannot prevent poor outcome after prolonged warm ischaemia of 7 h in this model. While the beneficial effects of surfactant replacement therapy have been observed in several experimental and clinical studies related to heart-beating donor lungs and cold ischaemia, it is unlikely that surfactant replacement therapy will overcome the shortage of organs in the context of prolonged warm ischaemia, for example, 7 h. Moreover, our data demonstrate that right heart function and dysfunctions of the pulmonary vascular bed are limiting factors that need to be addressed in NHBD.

[IV Consensus meeting of the Spanish Society of Liver Transplantation (SETH) 2012. Liver transplant with non-conventional grafts: Split liver transplantation and non-heart beating donors]. / IV Reunión de consenso de la Sociedad Española de Trasplante Hepático (SETH) 2012. Trasplante hepático con injertos no convencionales: bipartición hepática (split) y donante en asistolia.

The disbalance between the number of candidates to liver transplant and the number of liver grafts leads to waiting list mortality. Two potential ways of increasing the number of liver grafts are split liver transplantation and the transplantation of grafts from non-heart beating donors. Both of them were discussed in a consensus meeting of the Spanish Society of Liver Transplantation in October 2012. This paper outlines the conclusions of that meeting.

Advances in lung preservation.

After a brief review of conventional lung preservation, this article discusses the rationale behind ex vivo lung perfusion and how it has shifted the paradigm of organ preservation from conventional static cold ischemia to the utilization of functional normothermia, restoring the lung's own metabolism and its reparative processes. Technical aspects and previous clinical experience as well as opportunities to address specific donor organ injuries in a personalized medicine approach are also reviewed.

Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non-heart-beating donors.

OBJECTIVE: We sought to determine whether ventilation of lungs after death in non-heart-beating donors with carbon monoxide during warm ischemia and ex vivo lung perfusion and after transplant would reduce ischemia-reperfusion injury and improve lung function. METHODS: One hour after death, Sprague-Dawley rats were ventilated for another hour with 60% oxygen (control group) or 500 ppm carbon monoxide in 60% oxygen (CO-vent group; n=6/group). Then, lungs were flushed with 20 mL cold Perfadex, stored cold for 1 hour, then warmed to 37 °C in an ex vivo lung perfusion circuit perfused with Steen solution. At 37 °C, lungs were ventilated for 15 minutes with alveolar gas with or without 500 ppm carbon monoxide, then perfusion-cooled to 20 °C, flushed with cold Perfadex and stored cold for 2 hours. The left lung was transplanted using a modified cuff technique. Recipients were ventilated with 60% oxygen with or without carbon monoxide. One hour after transplant, we measured blood gases from the left pulmonary vein and aorta, and wet-to-dry ratio of both lungs. The RNA and protein extracted from graft lungs underwent real-time polymerase chain reaction and Western blotting, and measurement of cyclic guanosine monophosphate by enzyme-linked immunosorbent assay. RESULTS: Carbon monoxide ventilation begun 1 hour after death reduced wet/dry ratio after ex vivo lung perfusion. After transplantation, the carbon monoxide-ventilation group had better oxygenation; higher levels of tissue cyclic guanosine monophosphate, heme oxidase-1 expression, and p38 phosphorylation; reduced c-Jun N-terminal kinase phosphorylation; and reduced expression of interleukin-6 and interleukin-1ß messenger RNA. CONCLUSIONS: Administration of carbon monoxide to the deceased donor and non-heart-beating donor lungs reduces ischemia-reperfusion injury in rat lungs transplanted from non-heart-beating donors. Therapy to the deceased donor via the airway may improve post-transplant lung function.

Protective effects of ulinastatin on ischemia-reperfusion injury during rat non-heart beating donor lung transplantation / 中华器官移植杂志

Objective To investigate the protective effects of ulinastatin (UTI) on ischemiareperfusion injury of donor lungs,and the possible mechanism.Method Forty male SD rats were randomly divided into two groups:group C as control group and group U as UTI group.In group C donor lungs were antegradely flushed with 20 ml of cold (4 C) low potassium dextron (LPD) solution and 5 ml retrogradely.Meanwhile,in group U,UTI (500 000 U/L) was added in LPD solution and the same doses were used.According to the time after initiation of reperfusion,each group was divided into two subgroups:30 min (subgroup A) and 1 h (subgroup B).Arterial blood samples were collected for blood gas analysis.Lung samples were obtained at the end of reperfusion (30 min or 1 h).Microscopic examination of the donor lungs was conducted.Besides,the pulmonary water index (W/D),tissue malondialdehyde (MDA) and superoxide dismutase (SOD) content,and mRNA expression of tumor necrosis factor (TNF-a),intercellular adhesion molecule 1 (ICAM-1) and interleukin 10 (IL-10) were also measured.Results (1) One h after reperfusion,oxygenation index in group U was higher than that in group C (P =0.025) ; (2) The levels of W/D in subgroup A and subgroup B of group U were decreased as compared with group C (P =0.005 and P =0.006) ; (3)The microscopic changes of donor lung tissues in group U were lessen than in group C; (4) In subgroup A of group U,MDA content was decreased (P=0.039),and SOD content was increased (P=0.035),and similar results could be observed in subgroup B of group U (P =0.006 and P =0.030 respectively); (5) As compared with group C,the mRNA expression of TNF-α in group U was decreased at the time of 30 min after reperfusion (P =0.000),but no significant change was found at the time of 1 h (P =0.139).The mRNA expression of ICAM-1 was not decreased evidently at the time of 30 min (P=0.062),but significantly decreased at the time of 1 h (P=0.001).The mRNA expression of IL-10 was increased in subgroups A and B (P =0.004 and P =0.000 respectively).Conclusion This study demonstrated that UTI had protective effects of reducing ischemia-reperfusion injury on the donor lungs after lung transplantation in rat non-heart beating donor models.

Current status and recent advances of liver transplantation from donation after cardiac death.

The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a significant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably "prematurely" offered without ideal donor management or even prior to brain death being established. The absolute benefits of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.

Anesthesia for liver transplantation from a maastricht category 4 non-heart-beating donor -A case report-.

Great improvements in patient selection, surgical techniques, perioperative care, and immunosuppression have been made for the optimization of liver transplantation. To increase the number of organs available for liver transplantation, transplant centers have used marginal donors, split livers, living donors, or non-heart-beating donors (NHBDs). Despite recent enthusiasm for NHBDs in liver transplantation, warm ischemic injury to recovered organs has been an obstacle for the wide acceptance of NHBD. In the present case, we have conducted a liver transplantation from a Maastricht Category 4 NHBD. Warm ischemic time was 20 minutes and cold ischemic time was 5 hour 43 minutes. Consequently, the liver was successfully transplanted into the recipient.

Effects of HGF in Celsior solution on levels of INF-γ. IL-4 and IL-10 in a rat liver transplantation model / 中华肝胆外科杂志

Objective To explore the impact of recombinant human hepatocyte growth factor (rhHGF) in Celsior (CS) solution on the expression of INF-γ, IL-4 and IL-10 in a rat liver transplan-tation model. Methods After flushed with CS solution with addition of rhHGF (experimental group) or saline (control group), NHBD livers were stored at 4℃; for 16 h.then they were transplanted using the two-cuff technique with arterial reconstruction. The serum levels of INF-γ, IL-4 and IL-10 at lh after reperfusion were detected using ELISA. The INF-γ, IL-4 and IL-10 mRNA in the corresponding liver tissue were determined by RT-PCR. The 7-day survival rate was calculated and the histopatho-logical examination results were analyzed by hematoxylin and eosin staining. Results Compared with the control group, the experimental group showed lower INF-γ level and higher IL-4 and IL-10 levels in serum at 1 h after reperfusion (P<0. 05). The level of INF-γ mRNA in liver tissue was significant decreased at 1 h after reperfusion (P<0. 05) , and the level of IL-4 and IL-10 mRNA was significantly increased in the experimental group (P<0. 05). In experimental group, recipients got a better survival rate and histopathological examination showed a well-preserved hepatic architecture without hepatocyte necrosis, milder sinusoidal and portal congestion. Conclusion Adding exogenous rhHGF in CS solu-tion can protect NHBD livers from ischemia-reperfusion injury and prolong the survival in rats, which might be due to down-regulation of TNF-γ and up-regulation of IL-4 and IL-10.