The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time (CIT). This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time, transit time, and recipient surgery time, and is one of the most important donor-related risk factors which may influence the graft and recipient\'s survival. Recently, the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies. This review details the CIT definition and analyzes its different factors. It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.

The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included (n = 41 MP; n = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.

暂无摘要。

Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established. Previous studies used physiologically-based pharmacokinetic (PBPK) modeling to demonstrate that a decrease in hepatic transport and biliary excretion of the tracer molecule sodium fluorescein (SF) could correlate with increasing WIT in situ. Furthermore, these studies proposed intracellular sequestration of the hepatocyte canalicular membrane transporter multi-drug resistance-associated protein 2 (MRP2) leading to decreased MRP2 activity (maximal transport velocity; Vmax) as the potential mechanism for decreased biliary SF excretion. We adapted an extant PBPK model to account for ex vivo hepatic MP and fit a 6-parameter version of this model to control time course measurements of SF in MP perfusate and bile. We then identified parameters whose values were likely insensitive to changes in WIT and fixed them to generate a reduced model with only 3 unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT and found the mean estimated value for each parameter and compared them using a one-way ANOVA. We demonstrated that there was a significant decrease in the estimated value of Vmax for MRP2 at 30 min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP.

Optimizing graft preservation is key for ex-situ split grafts in pediatric liver transplantation (PSLT). Hypothermic Oxygenated Perfusion (HOPE) improves ischemia-reperfusion injury (IRI) and post-operative outcomes in adult LT. This study compares the use of HOPE in ex-situ partial grafts to static cold storage ex-situ partial grafts (SCS-Split) and to the gold standard living donor liver transplantation (LDLT). All consecutive HOPE-Split, SCS-Split and LDLT performed between 2018-2023 for pediatric recipients were included. Post-reperfusion syndrome (PRS, drop ≥30% in systolic arterial pressure) and reperfusion biopsies served as early indicators of IRI. We included 47 pediatric recipients (15 HOPE-Split, 17 SCS-Split, and 15 LDLT). In comparison to SCS-Split, HOPE-Split had a significantly shorter cold ischemia time (CIT) (470min vs. 538 min; p =0.02), lower PRS rates (13.3% vs. 47.1%; p = 0.04) and a lower IRI score (3 vs. 4; p = 0.03). The overall IRI score (3 vs. 3; p = 0.28) and PRS (13.3% vs. 13.3%; p = 1) after HOPE-Split were comparable to LDLT, despite a longer CIT (470 min vs. 117 min; p < 0.001). Surgical complications, one-year graft, and recipient survival did not differ among the groups. In conclusion, HOPE-Split mitigates early IRI in pediatric recipients in comparison to SCS-Split, approaching the gold standard of LDLT.

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The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2 h of SCS. Alternatively, machine perfusion (MP) is growing in the world of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved ex vivo for 24 h with either SNMP (n = 3) or SCS (n = 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14 days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2 weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS.

The shortage of organs for heart transplantation has created a need to explore the use of extended-criteria organs. We report the preliminary use of normothermic TransMedics Organ Care System-an ex vivo approach to preserve extended-criteria brain-dead donor hearts. This System maintains a normal temperature, provides continuous perfusion and oxygenation, reduces ischemic time, and enables additional viability assessment options. In a retrospective single-centre study conducted from April 2020 to March 2023, four extended criteria brain-dead donor hearts were perfused and monitored using the Organ Care System. Suitability for transplantation was assessed based on stable or decreasing lactate levels, along with appropriate perfusion parameters. The Organ Care for use of the Organ Care System were coronary artery disease, left ventricular hypertrophy, high-dose inotrope use in the donor, a downtime exceeding 20 min, and a left ventricular ejection fraction of 40-50%. Three out of the four donor hearts were transplanted, while one was discarded due to rising lactate concentration. The three recipients had a higher surgical risk profile for heart transplant. All showed normal cardiac function and no primary graft dysfunction postoperatively. At 2-3 years post-transplant, all recipients have a ventricular function of > 60%, with only one showing evidence of mild rejection. The Organ Care System enables the successful transplantation of marginal donor organs in high-risk recipients, showcasing the feasibility of recruiting donors with extended criteria. This technique is safe and promising, expanding the donor pool and addressing the organ shortage in heart transplantation in Hong Kong.

暂无摘要。

Intestinal allotransplantation was first described in the 1960s and successfully performed in the 1980s. Since that time, less progress has been made in the preservation of the allograft before transplantation and static cold storage remains the current standard. Normothermic machine perfusion represents an opportunity to simultaneously preserve, assess, and recondition the organ for transplantation and improve the procurement radius for allografts. The substantial progress made in the field during the last 60 years, coupled with the success of the preclinical animal model of machine perfusion-preserved intestinal transplantation, suggest we are approaching the point of clinical application.