Routine utilization of machine perfusion in liver transplantation:Ready for prime time?

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.

Hemoperfusion and continuous veno-venous hemodiafiltration for eliminating chlorfenapyr in poisoning patients

Chlorfenapyr is a liposoluble insecticide belonging to the pyrrole family.Chlorfenapyr is activated when the N-ethoxymethyl side chain breaks,forming a toxic metabolite,which uncouples oxidative phosphorylation in the mitochondria,inhibits the production of adenosine triphosphate (ATP),and leads to the death of cells and targe organisms.[1] Symptoms of chlorfenapyr poisoning in patients are mild and atypical in the early stage,especially in patients receiving low dose exposure;however,such cases are rare and may be ignored by physicians,often leading to delayed treatment.[2,3].

New strategy for distal limb perfusion in veno-arterial extracorporeal membrane oxygenation treatment: application of continuous renal replacement therapy tubing

Extracorporeal membrane oxygenation(ECMO)is a technology that can temporarily take over the functions of the heart and lungs.Acute kidney injury is a common issue in patients receiving ECMO treatment,with reported incidence rates ranging from 70%to 85%.[1]To maintain the balance of fluids and electrolytes in patients,continuous renal replacement therapy(CRRT)is frequently employed.

Early peripheral perfusion index predicts 28-day outcome in patients with septic shock

BACKGROUND:To investigate the prognostic value of the peripheral perfusion index(PPI)in patients with septic shock.METHODS:This prospective cohort study,conducted at the emergency intensive care unit of Peking University People's Hospital,recruited 200 patients with septic shock between January 2023 and August 2023.These patients were divided into survival(n=84)and death(n=116)groups based on 28-day outcomes.Clinical evaluations included laboratory tests and clinical scores,with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission.Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses.Receiver operator characteristic(ROC)curve was used to assess predictive performance.Mortality rates were compared,and Kaplan-Meier survival plots were created.RESULTS:Compared to the survival group,patients in the death group were older and had more severe liver damage and coagulation dysfunction,necessitating higher norepinephrine doses and increased fl uid replacement.Higher lactate levels and lower PPI levels at 0 h,6 h,and 12 h were observed in the death group.Multivariate Cox regression identifi ed prolonged prothrombin time(PT),decreased 6-h PPI and 12-h PPI as independent risk factors for death.The area under the curves for 6-h PPI and 12-h PPI were 0.802(95%CI 0.742-0.863,P<0.001)and 0.945(95%CI 0.915-0.974,P<0.001),respectively,which were superior to Glasgow Coma Scale(GCS),Sequential Organ Failure Assessment(SOFA)scores(0.864 and 0.928).Cumulative mortality in the low PPI groups at 6 h and 12 h was signifi cantly higher than in the high PPI groups(6-h PPI:77.52%vs.22.54%;12-h PPI:92.04%vs.13.79%,P<0.001).CONCLUSION:PPI may have value in predicting 28-day mortality in patients with septic shock.

Artificial intelligence software for assessing brain ischemic penumbra/core infarction on computed tomography perfusion:A real-world accuracy study

BACKGROUND With the increasingly extensive application of artificial intelligence(AI)in medical systems,the accuracy of AI in medical diagnosis in the real world deserves attention and objective evaluation.AIM To investigate the accuracy of AI diagnostic software(Shukun)in assessing ischemic penumbra/core infarction in acute ischemic stroke patients due to large vessel occlusion.METHODS From November 2021 to March 2022,consecutive acute stroke patients with large vessel occlusion who underwent mechanical thrombectomy(MT)post-Shukun AI penumbra assessment were included.Computed tomography angiography(CTA)and perfusion exams were analyzed by AI,reviewed by senior neurointerventional experts.In the case of divergences among the three experts,discussions were held to reach a final conclusion.When the results of AI were inconsistent with the neurointerventional experts’diagnosis,the diagnosis by AI was considered inaccurate.RESULTS A total of 22 patients were included in the study.The vascular recanalization rate was 90.9%,and 63.6%of patients had modified Rankin scale scores of 0-2 at the 3-month follow-up.The computed tomography(CT)perfusion diagnosis by Shukun(AI)was confirmed to be invalid in 3 patients(inaccuracy rate:13.6%).CONCLUSION AI(Shukun)has limits in assessing ischemic penumbra.Integrating clinical and imaging data(CT,CTA,and even magnetic resonance imaging)is crucial for MT decision-making.

Matched pair analysis of the effect of longer hypothermic machine perfusion time on kidney transplant outcomes

BACKGROUND Hypothermic machine perfusion(HMP)has demonstrated benefits in terms of early kidney transplant function compared to static cold storage.While longer preservation times have shown detrimental effects,a previous paired study indicated that longer pump times(the second kidney in a pair)might lead to improved outcomes.AIM To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience.METHODS A total of 61 pairs of transplant recipients who received kidneys from the same donor(2012-2021)were analyzed.Patients were divided into two groups depending on whether they were transplanted first(K1)or second(K2).Therefore,the patients in each pair had identical donor characteristics,except for time on the pump.Statistical analyses included Kaplan-Meyer analysis and paired tests,including McNemar's test,student's paired t-test,or Wilcoxon's test,as appropriate.RESULTS The two groups of recipients had similar demographics(age,body mass index,diabetes,time on dialysis,sensit-ization and retransplants).Cold ischemic times for K1 and K2 were 8.9(95%CI:7.9,9.8)and 14.7 hours(13.7,15.8)(P<0.0001),respectively.Overall,K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year(P=0.015).Delayed graft function was less common in K2,12/61(20%)than in K1,20/61(33%)(P=0.046).Finally,K2 showed a higher graft survival than K1(P=0.023).CONCLUSION Our results agree with a previous study that suggested possible advantages to longer pump times.Both studies should encourage further research into HMP's potential anti-inflammatory effect.

Normothermic regional perfusion mobile teams in controlled donation after circulatory death pathway: Evidence and peculiarities

To facilitate the implementation of controlled donation after circulatory death(cDCD)programs even in hospitals not equipped with a local Extracorporeal Membrane Oxygenation(ECMO)team(Spokes),some countries and Italian Regions have launched a local cDCD network with a ECMO mobile team who move from Hub hospitals to Spokes for normothermic regional perfusion(NRP)implantation in the setting of a cDCD pathway.While ECMO teams have been clearly defined by the Extracorporeal Life Support Organization,regarding composition,responsibilities and training programs,no clear,widely accepted indications are to date available for NRP teams.Although existing NRP mobile networks were developed due to the urgent need to increase the number of cDCDs,there is now the necessity for transplantation medicine to identify the peculiarities and responsibility of a NRP team for all those centers launching a cDCD pathway.Thus,in the present manuscript we summarized the character-istics of an ECMO mobile team,highlighting similarities and differences with the NRP mobile team.We also assessed existing evidence on NRP teams with the goal of identifying the characteristic and essential features of an NRP mobile team for a cDCD program,especially for those centers who are starting the program.Differences were identified between the mobile ECMO team and NRP mobile team.The common essential feature for both mobile teams is high skills and experience to reduce complications and,in the case of cDCD,to reduce the total warm ischemic time.Dedicated training programs should be developed for the launch of de novo NRP teams.

Liver graft preservation methods during cold ischemia phase and normothermic machine perfusion

The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.

Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant:What is the evidence?

The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.

Concise review of machine perfusion in liver transplantation

With the advances and clinical growth in liver transplantation over the last four decades the focus on expanding deceased donor organs has been in need of scientific research.In the past ten years several researchers have looked at the domain of machine perfusion as it applies to deceased donor livers.The following review focuses on the clinical trials and recent advances that will likely have the earliest entrance into the clinical arena.

Intestinal injury can be reduced by intra-arterial postischemic perfusion with hypertonic saline

AIM:To investigate the effect of local intestinal perfusion with hypertonic saline(HTS) on intestinal ischemia-reperfusion injury(IRI) in bothex vivo andin vivo rat models.METHODS:All experiments were performed on male Wistar rats anesthetized with pentobarbital sodium given intraperitoneally at a dose of 60 mg/kg.Ex vivo vascularly perfused rat intestine was subjected to 60-min ischemia and either 30-min reperfusion with isotonic buffer(controls),or 5 min with HTS of 365 or 415 mOsm/L osmolarity(HTS 365mOsm or HTS 415mOsm,respectively) followed by 25-min reperfusion with isotonic buffer.The vascular intestinal perfusate flow(IPF) rate was determined by collection of the effluent from the portal vein in a calibrated tube.Spontaneous intestinal contraction rate was monitored throughout.Irreversible intestinal injury or area of necrosis(AN) was evaluated histochemically using 2.3.5-triphenyltetrazolium chloride staining.In vivo,30-min ischemia was followed by either 30-min blood perfusion or 5-min reperfusion with HTS 365mOsm through the superior mesenteric artery(SMA) followed by 25-min blood perfusion.Arterial blood pressure(BP) was measured in the common carotid artery using a miniature pressure transducer.Histological injury was evaluated in both preparations using the Chui score.RESULTS:Ex vivo,intestinal IRI resulted in a reduction in the IPF rate during reperfusion(P < 0.05 vs sham).The postischemic recovery of the IPF rate did not differ between the controls and the HTS 365mOsm group.In the HTS 415mOsm group,postischemic IPF rates were lower than in the controls and the HTS 365mOsm group(P < 0.05).The intestinal contraction rate was similar at baseline in all groups.An increase in this parameter was observed during the first 10 min of reperfusion in the control group as compared to the sham-treated group,but no such increase was seen in the HTS 365mOsm group.In controls,AN averaged 14.8% ± 5.07% of the total tissue volume.Administration of HTS 365mOsm for 5 min after 60-min ischemia resulted in decrease in AN(5.1% ± 1.20% vs controls,P < 0.01).However,perfusion of the intestine with the HTS of greater osmolarity(HTS 415mOsm) failed to protect the intestine from irreversible injury.The Chiu score was lower in the HTS 365mOsm group in comparison with controls(2.4 ± 0.54 vs 3.2 ± 0.44,P = 0.042),while intestinal perfusion with HTS 415mOsm failed to improve the Chiu score.Intestinal reperfusion with HTS 365mOsm in the in vivo series secured rapid recovery of BP after its transient fall,whereas in the controls no recovery was seen.The Chiu score was lower in the HTS 365mOsm group vs controls(3.1 ± 0.26 and 3.8 ± 0.22,P = 0.0079 respectively,),although the magnitude of the effect was lower than in the ex vivo series.CONCLUSION:Brief intestinal postischemic perfusion with HTS 365mOsm through the SMA followed by blood flow restoration is a protective procedure that could be used for the prevention of intestinal IRI.

Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion

Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.

Cerebral perfusion in corresponding blood supply areas of transient ischemic attack patients with intracranial stenosis Seven cases of diamox-perfusion verified by magnetic resonance-perfusion-weighted imaging

BACKGROUND： Due to collateral circulation and cerebrovascular reserve, arterial stenosis and reduced cerebral blood flow may not necessarily indicate impaired cerebral peffusion. Therefore, according to degree of stenosis and clinical symptoms, interventional surgery to relieve arterial stenosis in transient ischemic attack （TIA） patients with major intracranial stenosis is imprudent. Rather, cerebral perfusion and reserve capacity are direct indicators for the assessment of degree and presence of cerebral ischemia. OBJECTIVE： To evaluate cerebral perfusion and reserve in TIA patients with major intracranial stenosis or occlusion using magnetic resonance-perfusion-weighted imaging （MR-PWl） data prior to and following diamox administration. DESIGN, TIME AND SETTING： A self-comparative, neuroimaging observation was performed at the Neurological Department and Radiological Center of the First Affiliated Hospital of Jinan University between December 2007 and April 2009. PARTICIPANTS： Seven acute TIA patients, who were admitted to the Neurological Department of the First Affiliated Hospital of Jinan University between December 2007 and April 2009, were enrolled in the present study. Magnetic resonance imaging confirmed that no acute cerebral infarction happened, nor did bleeding exist. Magnetic resonance angiography, transcranial Doppler ultrasound, and/or digital subtraction angiography confirmed the presence of major intracranial arterial stenosis. Clinical symptoms corresponded to blood supplying regions of the arterial stenosis. METHODS： Baseline MR-PWI was performed on seven patients with intracranial stenosis or occlusion. Two grams of acetazolamide （diamox） were orally administered after 2 days. A second PWl was performed after 2 hours to compare cerebral perfusion parameters prior to and following diamox administration. MAIN OUTCOME MEASURES： PWI results of cerebral perfusion prior to and following diamox administration. RESULTS： The baseline PWl from five patients indicated decreased cerebral perfusion areas. Following oral administration of diamox, cerebral perfusion significantly decreased in those areas. Moreover, new areas of decreased cerebral perfusion were observed in two out of the five patients. In one patient, no significant decrease in cerebral perfusion was found. In another patient, baseline PWl indicated decreased cerebral perfusion in the left hemisphere. However, normal perfusion was observed in both cerebral lobes following diamox administration. CONCLUSION： TIA patients with intracranial stenosis, who are diagnosed by PWI and exhibited decreased cerebral perfusion and reserve, might require further treatment such as intervention by angioptasty.

Machine perfusion of the liver: Which is the best technique to mitigate ischaemia-reperfusion injury?

Longstanding research describes the mechanisms whereby the restoration of blood flow and reoxygenation(reperfusion) aggravates the ischaemic injury caused by a period of anoxia to a donor liver. This phenomenon, called ischaemia-reperfusion injury(IRI), leads to parenchymal cell death,microcirculatory failure, and inflammatory immune response. Clinically, IRI is the main factor responsible for the occurrence of posttransplant graft dysfunction and ischaemic-type biliary lesions. While extended criteria donor livers are more vulnerable to IRI, their utilisation is required to address the shortfall in donor organs. Thus, the mitigation of IRI should drive the setting of a new benchmark for marginal organ preservation. Herein, strategies incorporating different modalities of machine perfusion of the liver to alleviate IRI are discussed in conjunction with advantages and disadvantages of individual protocols.Techniques leading to reperfusion of the liver during machine perfusion(in situ normothermic regional perfusion and ex situ normothermic machine perfusion)may mitigate IRI by shortening the ischaemic period of the organs. This benefit potentially escalates from the minimum level, obtained following just partial alleviation of the ischaemic period, to the maximum level, which can be potentially achieved with ischaemia-free organ transplantation. Techniques that do not lead to reperfusion of the liver during machine perfusion(hypothermic,subnormothermic, and controlled-oxygenated rewarming) optimise mitochondrial oxidative function and replenish cellular energy stores, thereby lowering reactive oxygen species production as well as the activation ofdownstream inflammatory pathways during reperfusion. Further mechanistic insights into IRI may guide the development of donor-specific protocols of machine perfusion on the basis of the limitations of individual categories of extended criteria donor organs.

Mucosal blood flow measurements using laser Doppler perfusion monitoring

Perfusion of individual tissues is a basic physiological process that is necessary to sustain oxygenation and nutrition at a cellular level. Ischemia, or the insuff iciency of perfusion, is a common mechanism for tissue death or degeneration, and at a lower threshold, a mechanism for the generation of sensory signalling including pain. It is of considerable interest to study perfusion of pe- ripheral abdominal tissues in a variety of circumstances. Microvascular disease of the abdominal organs has been implicated in the pathogenesis of a variety of disorders, including peptic ulcer disease, inflammatory bowel disease and chest pain. The basic principle of laser Doppler perfusion monitoring (LDPM) is to analyze changes in the spectrum of light reflected from tissues as a response to a beam of monochromatic laser light emitted. It reflects the total local microcirculatory blood perfusion, including perfusion in capillaries, arterioles, venules and shunts. During the last 20-25 years, numerous studies have been performed in different parts of the gastroin-testinal (GI) tract using LDPM. In recent years we have developed a multi-modal catheter device which includes a laser Doppler probe, with the intent primarily to investigate patients suffering from functional chest pain of presumed oesophageal origin. Preliminary studies show the feasibility of incorporating LDPM into such catheters for performing physiological studies in the GI tract. LDPM has emerged as a research and clinical tool in preference to other methods; but, it is important to be aware of its limitations and account for them when reporting results.

Current and future perspectives on acute-on-chronic liver failure: Challenges of transplantation, machine perfusion, and beyond

Acute-on-chronic liver failure(ACLF)is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation,organ failure and high short-term mortality.Partially due to the lack of universal diagnostic criteria,the actual ACLF prevalence remains unclear;nevertheless,it is expected to be a highly prevalent condition worldwide.Earlier transplantation is an effective protective measure for selected ACLF patients.Besides liver transplantation,diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy.Although new clinical specific therapies have been researched,more studies are necessary to assess safety and efficacy.Therefore,future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow.Thus,an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality.In addition,while donor organ quality is meant to be a prognostic factor in the ACLF setting,recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.

Ex vivo limb perfusion for traumatic amputation in military medicine

Background:Limb loss has a drastic impact on a patient’s life.Severe trauma to the extremities is common in current military conflicts.Among other aspects,"life before limb"damage control surgery hinders immediate replantation within the short post-traumatic timeframe,which is limited in part by the ischemic time for successful replantation.Ex vivo limb perfusion is currently being researched in animal models and shows promising results for its application in human limb replantation and allotransplantation.Presentation of the hypothesis:The current lack of replantation possibilities in military operations with high rates of amputation can be addressed with the development of a portable ex vivo limb perfusion device,as there are several opportunities present with the introduction of this technique on the horizon.We hypothesize that ex vivo limb perfusion will enable overcoming the critical ischemic time,provide surgical opportunities such as preparation of the stump and limb,allow for spare-part surgery,enable rigorous antibiotic treatment of the limb,reduce ischemiareperfusion injuries,enable a tissue function assessment before replantation,and enable the development of large limb transplant programs.Testing the hypothesis:Data from in vivo studies in porcine models are limited by the relatively short perfusion time of 24 h.In the military setting,notably longer perfusion times need to be realized.Therefore,future animal studies must focus especially on long-term perfusion,since this represents the military setting,considering the time for stabilization of the patient until evacuation to a tertiary treatment center.Implications of the hypothesis:The development and clinical introduction of ex vivo limb perfusion in the military setting could lead to a drastic reduction in the number of limb amputations among service members.Ex vivo limb perfusion enables replantation surgery in Role 4 facilities and changes the clinical setting from a highly urgent,lifethreatening situation to a highly methodical,well-prepared starting point for optimal treatment of the wounded service member.With its introduction,the principle of"life before limb"will change to"life before limb before elective replantation/allotransplantation after ex vivo limb perfusion".

Polyethylene glycols: An effective strategy for limiting liver ischemia reperfusion injury

Liver ischemia-reperfusion injury(IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ(ischemia) is exacerbated following the return of oxygen delivery(reperfusion). IRI is a major cause of primary nonfunction after transplantation and may lead to graft rejection, regardless of immunological considerations. The immediate response involves the disruption of cellular mitochondrial oxidative phosphorylation and the accumulation of metabolic intermediates during the ischemic period, and oxidative stress during blood flow restoration. Moreover, a complex cascade of inflammatory mediators is generated during reperfusion, contributing to the extension of the damage and finally to organ failure. A variety of pharmacological interventions(antioxidants, anticytokines, etc.) have been proposed to alleviate graft injury but their usefulness is limited by the local and specific action of the drugs and by their potential undesirable toxic effects. Polyethylene glycols(PEGs), which are non-toxic water-soluble compounds approved by the FDA, have been widely used as a vehicle or a base in food, cosmetics and pharmaceuticals, and also as adjuvants for ameliorating drug pharmacokinetics. Some PEGs are also currently used as additives in organ preservation solutions prior to transplantation in order to limit the damage associated with cold ischemia reperfusion. More recently, the administration of PEGs of different molecular weights by intravenous injection has emerged as a new therapeutic tool to protect liver grafts from IRI. In this review, we summarize the current knowledge concerning the use of PEGs as a useful target for limiting liver IRI.

Therapeutics administered during ex vivo liver machine perfusion:An overview

Although the use of extended criteria donors has increased the pool of available livers for transplant,it has also introduced the need to develop improved methods of protection against ischemia-reperfusion injury(IRI),as these"marginal"organs are particularly vulnerable to IRI during the process of procurement,preservation,surgery,and post-transplantation.In this review,we explore the current basic science research investigating therapeutics administered during ex vivo liver machine perfusion aimed at mitigating the effects of IRI in the liver transplantation process.These various categories of therapeutics are utilized during the perfusion process and include invoking the RNA interference pathway,utilizing defatting cocktails,and administering classes of agents such as vasodilators,anti-inflammatory drugs,human liver stem cell-derived extracellular vesicles,and δ-opioid agonists in order to reduce the damage of IRI.Ex vivo machine perfusion is an attractive alternative to static cold storage due to its ability to continuously perfuse the organ,effectively deliver substrates and oxygen required for cellular metabolism,therapeutically administer pharmacological or cytoprotective agents,and continuously monitor organ viability during perfusion.The use of administered therapeutics during machine liver perfusion has demonstrated promising results in basic science studies.While novel therapeutic approaches to combat IRI are being developed through basic science research,their use in clinical medicine and treatment in patients for liver transplantation has yet to be explored.

Computed tomography perfusion study of hemodynamic changes and portal hyperperfusion in a rabbit model of small-for-size liver

BACKGROUND:Portal hyperperfusion in the small-for-size (SFS) liver can threaten survival of rabbits.Therefore,it is important to understand the hemodynamic changes in the SFS liver.METHODS:Twenty rabbits were divided into two groups:a control group and a modulation group.The control group underwent an extended hepatectomy.The modulation group underwent the same procedure plus splenectomy to reduce portal blood flow.CT perfusion examinations were performed on all rabbits before and after operation.Perfusion parameter values,especially portal vein perfusion (PVP),were analyzed.RESULTS:PVP in the modulation group was lower than in the control group after operation (P=0.002).In the control group,postoperative PVP increased by 193.7±55.1% compared with preoperative PVP.A weak correlation was found between the increased percentage of PVP and resected liver-to-body weight ratio (RLBWR) (r=0.465,P=0.033).In the modulation group,postoperative PVP increased by 101.4±32.5%.No correlation was found between the increased percentage of PVP and RLBWR (r=0.167,P=0.644).Correlations were found between PVP and serum alanine aminotransferase,aspartate aminotransferase,and total bilirubin after surgery (P<0.05).CONCLUSION:We successfully evaluated the characteristics of hemodynamic changes as well as the effects of splenectomy in the SFS liver in rabbits by the CT technique.