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Frontiers in Immunology 2022The frequent use of marginal livers forces transplant centres to explore novel technologies to improve organ quality and outcomes after implantation. Organ perfusion... (Review)
Review
The frequent use of marginal livers forces transplant centres to explore novel technologies to improve organ quality and outcomes after implantation. Organ perfusion techniques are therefore frequently discussed with an ever-increasing number of experimental and clinical studies. Two main approaches, hypothermic and normothermic perfusion, are the leading strategies to be introduced in clinical practice in many western countries today. Despite this success, the number of studies, which provide robust data on the underlying mechanisms of protection conveyed through this technology remains scarce, particularly in context of different stages of ischemia-reperfusion-injury (IRI). Prior to a successful clinical implementation of machine perfusion, the concept of IRI and potential key molecules, which should be addressed to reduce IRI-associated inflammation, requires a better exploration. During ischemia, Krebs cycle metabolites, including succinate play a crucial role with their direct impact on the production of reactive oxygen species (ROS) at mitochondrial complex I upon reperfusion. Such features are even more pronounced under normothermic conditions and lead to even higher levels of downstream inflammation. The direct consequence appears with an activation of the innate immune system. The number of articles, which focus on the impact of machine perfusion with and without the use of specific perfusate additives to modulate the inflammatory cascade after transplantation is very small. This review describes first, the subcellular processes found in mitochondria, which instigate the IRI cascade together with proinflammatory downstream effects and their link to the innate immune system. Next, the impact of currently established machine perfusion strategies is described with a focus on protective mechanisms known for the different perfusion approaches. Finally, the role of such dynamic preservation techniques to deliver specific agents, which appear currently of interest to modulate this posttransplant inflammation, is discussed together with future aspects in this field.
Topics: Humans; Immunity; Inflammation; Liver Transplantation; Organ Preservation; Perfusion
PubMed: 35874758
DOI: 10.3389/fimmu.2022.855263 -
Transplant International : Official... 2022Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard clinically. However, machine perfusion (MP) is considered an... (Review)
Review
Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard clinically. However, machine perfusion (MP) is considered an approach for donor organ management to extend the donor pool and/or increase the utilization rate. This review summarizes and critically assesses the available clinical data on MP in heart transplantation. We searched Medline (PubMed), Cochrane, Embase, and clinicaltrials.gov, along with reference lists of the included publications and identified 40 publications, including 18 articles, 17 conference abstracts, and five ongoing clinical trials. Two types of MP were used: hypothermic MP (HMP) and normothermic MP (NMP). Three studies evaluated HMP, and 32 evaluated NMP. Independent of the system, MP resulted in clinical outcomes comparable to traditional SCS. However, NMP seemed especially beneficial for high-risk cases and donation after circulatory death (DCD) hearts. Based on currently available data, MP is non-inferior to standard SCS. Additionally, single-centre studies suggest that NMP could preserve the hearts from donors outside standard acceptability criteria and DCD hearts with comparable results to SCS. Finally, HMP is theoretically safer and simpler to use than NMP. If a machine malfunction or user error occurs, NMP, which perfuses a beating heart, would have a narrower margin of safety. However, further well-designed studies need to be conducted to draw clear conclusions.
Topics: Heart; Heart Transplantation; Humans; Organ Preservation; Perfusion; Tissue Donors
PubMed: 35401041
DOI: 10.3389/ti.2022.10258 -
American Journal of Transplantation :... Apr 2021Normothermic machine perfusion (NMP) technologies are emerging as an important adjunct in organ preservation and transplantation. NMP can enable the reduction or...
Normothermic machine perfusion (NMP) technologies are emerging as an important adjunct in organ preservation and transplantation. NMP can enable the reduction or avoidance of cold ischemia and allows for pretransplant measurement of function and metabolic status to assess the suitability of the organ for transplantation. The key requirement of NMP is to provide an environment that is protective to the organ, ensures optimal oxygen delivery and supports metabolic function. Red blood cell-based solutions, artificial hemoglobin solutions, and acellular solutions have all been utilized in NMP. However, there is no clear consensus on perfusion protocols. A period of NMP after hypothermic preservation is the most commonly used strategy. As an alternative, several groups have developed and tested the feasibility of more prolonged periods of NMP. There are only a few reports of the application of NMP in clinical kidney transplantation and each uses different approach and conditions. This review details the rationale for NMP protocols considering duration of NMP and different perfusate compositions in experimental and clinical models. We also include a discussion on the mechanistic action of NMP, comparison of subnormothermic and hypothermic conditions, the different logistical approaches and future requirements.
Topics: Cold Ischemia; Kidney; Kidney Transplantation; Organ Preservation; Perfusion; Review Literature as Topic
PubMed: 32897651
DOI: 10.1111/ajt.16307 -
Transplantation Nov 2021The use of cold preservation solutions to rapidly flush and cool the kidney followed by static cold storage in ice has been the standard kidney preservation technique... (Review)
Review
The use of cold preservation solutions to rapidly flush and cool the kidney followed by static cold storage in ice has been the standard kidney preservation technique for the last 50 y. Nonetheless, changing donor demographics that include organs from extended criteria donors and donation after circulatory death donors have led to the adoption of more diverse techniques of preservation. Comparison of hypothermic machine perfusion and static cold storage techniques for deceased donor kidneys has long been debated and is still contested by some. The recent modification of hypothermic machine perfusion techniques with the addition of oxygen or perfusion at subnormothermic or near-normothermic temperatures are promising strategies that are emerging in clinical practice. In addition, the use of normothermic regional perfusion to resuscitate abdominal organs of donation after circulatory death donors in situ before cold flushing is also increasingly being utilized. This review provides a synopsis of the different types of preservation techniques including their mechanistic effects and the outcome of their application in clinical practice for different types of donor kidney.
Topics: Graft Survival; Kidney; Kidney Transplantation; Organ Preservation; Perfusion; Tissue Donors
PubMed: 33982904
DOI: 10.1097/TP.0000000000003679 -
The Journal of Extra-corporeal... Mar 2022A diverse and equitable working environment is desirable. In 2011, a survey was distributed to all female perfusionists in the United States. This survey suggested that...
A diverse and equitable working environment is desirable. In 2011, a survey was distributed to all female perfusionists in the United States. This survey suggested that the female perfusionists share the same difficulties as women in the labor force. The role of women in society in general is clearly changing. Female perfusionists have been part of that evolution. Promoting equality and respecting diversity are central to life today. A follow-up survey was distributed to evaluate the status and the change in gender stereotypes in the field of perfusion over the past 10 years. Women make up nearly half of the U.S. labor force and 35.7% of the present perfusion workforce in North America (1,077 certified women). Women make 82 cents for every dollar that men earn and this disparity widens for women with more education. The purpose of this survey was to poll women in perfusion to evaluate concerns and opinions in their careers and to compare to the 2011 survey results. In December 2021, a 39-question survey (surveymonkey.com, San Mateo, CA) was made available to all female perfusionists in North American via social media websites (Facebook.com, Perfusion.com, LinkedIn.com, Perflist, Perfmail, and FPP Listserv). There were 384 responses to the 2021 survey compared to the 538 responses in 2011. About 32.1% of the survey participants have been used in perfusion for more than 20 years; 37.6% have earned a master's degree compared to 2011, where 18.3% had master's level education; 72.5% are the financial providers for their family with 44.2% earning $101-150,000.00 and 40.3% greater than $200,000.00, which is a significant change from 2011; 61.5% consider themselves under moderate stress compared to 63.0% in 2011; 94.3% take call on a regular basis; and 74.1% feel they miss essential family functions because of their schedules. Similarly, 62.8% felt discriminated against because of gender compared to 50.9% in 2011. This survey suggests that the female perfusionists have shown to be assertive (72% are the primary financial supporter of their families) and competent in the field of cardiovascular perfusion (nearly 40% have masters degrees). Further analysis is needed to discern whether female perfusionists are treated with comparable respect as their male colleagues when 50.0% report some discrimination or harassment in their workplace.
Topics: Female; Male; Humans; United States; Perfusion; Workforce; Surveys and Questionnaires; Certification
PubMed: 36380828
DOI: 10.1182/ject-29-34 -
Multimedia Manual of Cardiothoracic... Apr 2023Available donor organs for lung transplantation are scarce. Ex vivo lung perfusion provides a platform to preserve, assess, and recondition donor lungs and can thereby...
Available donor organs for lung transplantation are scarce. Ex vivo lung perfusion provides a platform to preserve, assess, and recondition donor lungs and can thereby aid in enlarging the donor pool. This video tutorial discusses the indications, preparation, and surgical technique for and the initiation, maintenance and termination of the ex vivo lung perfusion procedure.
Topics: Humans; Perfusion; Lung; Extracorporeal Circulation; Lung Transplantation; Tissue Donors
PubMed: 37010027
DOI: 10.1510/mmcts.2023.011 -
Journal of Hepatology Jun 2022The development of cholangiopathies after liver transplantation impacts on the quality and duration of graft and patient survival, contributing to higher costs as... (Review)
Review
The development of cholangiopathies after liver transplantation impacts on the quality and duration of graft and patient survival, contributing to higher costs as numerous interventions are required to treat strictures and infections at the biliary tree. Prolonged donor warm ischaemia time in combination with additional cold storage are key risk factors for the development of biliary strictures. Based on this, the clinical implementation of dynamic preservation strategies is a current hot topic in the field of donation after circulatory death (DCD) liver transplantation. Despite various retrospective studies reporting promising results, also regarding biliary complications, there are only a few randomised-controlled trials on machine perfusion. Recently, the group from Groningen has published the first randomised-controlled trial on hypothermic oxygenated perfusion (HOPE), demonstrating a significant reduction of symptomatic ischaemic cholangiopathies with the use of a short period of HOPE before DCD liver implantation. The most likely mechanism for this important effect, also shown in several experimental studies, is based on mitochondrial reprogramming under hypothermic aerobic conditions, e.g. exposure to oxygen in the cold, with a controlled and slow metabolism of ischaemically accumulated succinate and simultaneous ATP replenishment. This unique feature prevents mitochondrial oxidative injury and further downstream tissue inflammation. HOPE treatment therefore supports livers by protecting them from ischaemia-reperfusion injury (IRI), and thereby also prevents the development of post-transplant biliary injury. With reduced IRI-associated inflammation, recipients are also protected from activation of the innate immune system, with less acute rejections seen after HOPE.
Topics: Constriction, Pathologic; Graft Survival; Humans; Inflammation; Organ Preservation; Perfusion; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 35589254
DOI: 10.1016/j.jhep.2022.01.024 -
International Survey of Perfusion Practice for Pediatric and Congenital Heart Surgery: 2021 Results.The Journal of Extra-corporeal... Dec 2022The conduct of cardiopulmonary bypass in neonatal, infant, and pediatric patients continuously evolves as new devices and innovative techniques are introduced. Since...
The conduct of cardiopulmonary bypass in neonatal, infant, and pediatric patients continuously evolves as new devices and innovative techniques are introduced. Since 1989, periodic pediatric perfusion surveys have been conducted to ascertain practice patterns involving demographics, equipment, and perfusion techniques. The goal of this current project is to provide an updated perspective on international pediatric and congenital perfusion practice since the last survey conducted in 2016. In July 2021, a 100-question perfusion survey was distributed to 284 pediatric cardiac surgery centers using a secure web browser-based data application. Each center was given a unique survey hyperlink to ensure one response per institution and to monitor the response rate. Centers were given 1 month to complete the survey and electronic reminders were sent weekly to nonrespondents. After the survey was closed, information from completed surveys was exported to a software program for analysis. Responses were received from 153 of 284 pediatric centers for a response rate of 54%. Sixty respondents (39%) were from North American (NA) centers while 93 respondents (61%) were from non-North American (NNA) centers. The vast majority of centers use a roller head arterial pump (93%), hollow fiber oxygenators with open reservoirs (86%), and integrated arterial line filters (73%). The use of modified ultrafiltration was reported by 76% of centers. Ninety-two percent of centers reported the use of selective antegrade cerebral perfusion for aortic arch repairs. The N + 1 staffing model was most prevalent (52%), followed by two perfusionists per case (33%). Periodic surveys continue to be a useful modality in assessing regional variation in pediatric perfusion practice. This survey marked the first time the majority of responses came from non-North American institutions. Identifying these practice patterns may aid in the development of, and adherence to, regional standards and guidelines. This would foster the reduction of variation in practice and potentially improve patient safety.
Topics: Infant; Infant, Newborn; Child; Humans; Perfusion; Surveys and Questionnaires; Cardiopulmonary Bypass; Cardiac Surgical Procedures; Heart Defects, Congenital
PubMed: 36742024
DOI: 10.1182/ject-2200012 -
The British Journal of Surgery May 2021Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate...
BACKGROUND
Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate biochemistry and significant perfusion-induced oedema are reported universally. Optimizing perfusion protocols is therefore essential for maintaining tissue health.
METHODS
A randomized, two-stage open preclinical trial design was used to determine the optimal temperature and mean arterial pressure for machine perfusion. Conditions compared were: normothermic machine perfusion at 70 mmHg (NMP-70); subnormothermic perfusion (28°C) at 70 mmHg; subnormothermic (28°C) perfusion at 50 mmHg; and hypothermic perfusion (10°C) at 30 mmHg. Following this, a head-to-head experiment was undertaken comparing the optimal machine perfusion with static cold storage. Paired bilateral limbs (10 in total) were randomized to either 8 h of static cold storage, or 2 h of static cold storage and 6 h of optimal machine perfusion. Both groups of limbs were then reperfused on a circuit primed with matched blood from unrelated donors for 4 h without immunosuppression.
RESULTS
NMP-70 resulted in less tissue injury and stable perfusion biochemistry. Assessing reperfusion outcomes, static cold storage resulted in acidosis with increased lactate and a worsening electrolyte profile, necessitating bolus infusions of bicarbonate to prevent graft loss. Conversely, NMP-70 was associated with haemodynamic and biochemical stability. Histologically, on reperfusion with allogeneic whole blood, limbs subjected to static cold storage exhibited multifocal ischaemic injury and increased inflammation, which was absent with NMP-70. Static cold storage also resulted in significant oedema compared with NMP-70.
CONCLUSION
Normothermic perfusion resulted in superior graft preservation and less reperfusion injury compared with the current static cold storage protocol.
Topics: Animals; Blood Pressure; Composite Tissue Allografts; Graft Survival; Models, Animal; Perfusion; Random Allocation; Reperfusion Injury; Specimen Handling; Swine; Temperature
PubMed: 34043778
DOI: 10.1002/bjs.11921 -
American Journal of Transplantation :... May 2022Pancreas transplantation improves and extends the life of patients with insulin-dependent diabetes. Pancreata from extended criteria donors have been increasingly used...
Pancreas transplantation improves and extends the life of patients with insulin-dependent diabetes. Pancreata from extended criteria donors have been increasingly used due to the scarcity of available grafts. Normothermic ex situ pancreas perfusion (NESPP) can keep grafts metabolically active, potentially allowing for assessment and organ repair, and could improve outcomes of marginal grafts. A novel NESPP technique was developed and tested. Porcine pancreata were removed after a short period of warm ischemia and subjected to 6 h of NESPP. Perfusion parameters, potential graft assessment markers and graft injury were measured. Next, pancreata subjected to 3 h of NESPP were transplanted and animals were followed for up to 3 days. Graft function and injury post-transplantation were evaluated. Using this novel system of perfusion, pancreata were perfused for an extended period of time with minimal edema. Histology at the end of perfusion showed intact islet cells with only mild signs of tissue injury. NESPP transplanted grafts showed immediate function after transplantation, with glucose levels in normal range. NESPP maintains a physiologic environment and excellent graft function without causing significant graft injury. Porcine pancreas transplantation is feasible and allows for in vivo graft assessment of pancreas function and injury after NESPP.
Topics: Animals; Humans; Organ Preservation; Pancreas; Pancreas Transplantation; Perfusion; Swine; Warm Ischemia
PubMed: 35258859
DOI: 10.1111/ajt.17019