The Differential Impact of Early Graft Dysfunction in Kidney Donation After Brain Death and After Circulatory Death: Insights from the Dutch National Transplant Registry.

Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcome. Using competing risk and cox regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within seven days after transplantation), slow graft function (SGF, three-day plasma creatinine decline less than 10% per day), and immediate graft function (IGF). In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios [aHR]: DGF in DBD: 1.79 [1.04- 2.91], p = 0.027, DGF in DCD: 1.84 [1.18 - 2.87], p = 0.008; Reference: no DGF). SGF was associated with death-censored graft loss in DBD, but not significantly in DCD (aHR DBD: 2.82 (1.34 - 5.93), p = 0.007, and DCD: 1.54 (0.72 - 3.35), p = 0.262; Reference: IGF). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic.

Expression of c-jun/c-fos mRNA Indicates Persistent Myocardial Stretch During Asphyxia-Induced Cardiac Arrest.

Right ventricular dysfunction is a key clinical issue for the viability of donation-after-circulatory-death (DCD) heart transplantation. DCD hearts with volume overload have the potential to exhibit aggravated right ventricular dysfunction following heart transplantation. The c-jun/c-fos mRNAs are genes that immediately respond to myocardial cell stretch. We assessed myocardial cell stretch during asphyxia-induced cardiac arrest by measuring c-jun/c-fos mRNA expression levels. The trachea was dissected and ligated to initiate asphyxiation in anesthetized Wistar rats under paralyzed ventilation. The hearts were harvested at 4 time points: 0, 15, 30, and 45 minutes after the termination of ventilation. Free walls of the right and left ventricles and the interventricular septum were sectioned. Total RNA was extracted from these tissues, and cDNA was synthesized using reverse transcription. The c-jun/c-fos mRNA expression levels were quantified using the droplet digital polymerase chain reaction method. In the left ventricle, c-jun/c-fos expression levels rapidly increased at 15 minutes, but the expression levels returned to the baseline level at 30 minutes after tracheal ligation. In contrast, in the right ventricle, c-jun/c-fos expression levels gradually increased and peaked 30 minutes after tracheal ligation. Myocardial cell stretching in the right ventricle is prolonged after asphyxia-induced cardiac arrest compared to that in the left ventricle, which may lead to right ventricular dysfunction after DCD heart transplantation.

Normothermic Regional Perfusion in Controlled Donation After Circulatory Death Liver Transplantation: A Systematic Review and Meta-Analysis.

Liver grafts from controlled donation after circulatory death (cDCD) donors have lower utilization rates due to inferior graft and patient survival rates, largely attributable to the increased incidence of ischemic cholangiopathy, when compared with grafts from brain dead donors (DBD). Normothermic regional perfusion (NRP) may improve the quality of cDCD livers to allow for expansion of the donor pool, helping to alleviate the shortage of transplantable grafts. A systematic review and metanalysis was conducted comparing NRP cDCD livers with both non-NRP cDCD livers and DBD livers. In comparison to non-NRP cDCD outcomes, NRP cDCD grafts had lower rates of ischemic cholangiopathy [RR = 0.23, 95% CI (0.11, 0.49), p = 0.0002], primary non-function [RR = 0.51, 95% CI (0.27, 0.97), p = 0.04], and recipient death [HR = 0.5, 95% CI (0.36, 0.69), p < 0.0001]. There was no difference in outcomes between NRP cDCD donation compared to DBD liver donation. In conclusion, NRP improved the quality of cDCD livers compared to their non-NRP counterparts. NRP cDCD livers had similar outcomes to DBD grafts. This provides further evidence supporting the continued use of NRP in cDCD liver transplantation and offers weight to proposals for its more widespread adoption.

Expanding Horizons in Cardiac Transplant: Efficacy and Outcomes of Circulatory and Brain Death Donor Hearts in a Newly Implemented Cardiac Transplant Program with Limited Donor Accessibility and a Literature Review.

(1) Background: Cardiac donation after circulatory death (DCD) is an emerging paradigm in organ transplantation. However, this technique is recent and has only been implemented by highly experienced centers. This study compares the characteristics and outcomes of thoraco-abdominal normothermic regional perfusion (TANRP) and static cold-storage DCD and traditional donation after brain death (DBD) cardiac transplants (CT) in a newly stablished transplant program with restricted donor availability. (2) Method: We performed a retrospective, single-center study of all adult patients who underwent a CT between November 2019 and December 2023, with a follow-up conducted until August 2024. Data were retrieved from medical records. A review of the current literature on DCD CT was conducted to provide a broader context for our findings. The primary outcome was survival at 6 months after transplantation. (3) Results: During the study period, 76 adults (median age 56 years [IQR: 50-63 years]) underwent CT, and 12 (16%) were DCD donors. DCD donors had a similar age (46 vs. 47 years, p = 0.727), were mostly male (92%), and one patient had left ventricular dysfunction during the intraoperative DCD process. There were no significant differences in recipients' characteristics. Survival was similar in the DCD group compared to DBD at 6 months (100 vs. 94%) and 12 months post-CT survival (92% vs. 94%), p = 0.82. There was no primary graft dysfunction in the DCD group (9% in DBD, p = 0.581). The median total hospital stay was longer in the DCD group (46 vs. 21 days, p = 0.021). An increase of 150% in transplantation activity due to DCD was estimated. (4) Conclusions: In a new CT program that utilized older donors and included recipients with similar illnesses and comorbidities, comparable outcomes between DCD and DBD hearts were observed. DCD was rapidly incorporated into the transplant activity, demonstrating an expedited learning curve and significantly increasing the availability of donor hearts.

Liver function maximum capacity test during normothermic regional perfusion predicts graft function after transplantation.

Purpose: In an effort to reduce waitlist mortality, extended criteria donor organs, including those from donation after circulatory death (DCD), are being used with increasing frequency. These donors carry an increased risk for postoperative complications, and balancing donor-recipient risks is currently based on generalized nomograms. Abdominal normothermic regional perfusion (aNRP) enables individual evaluation of DCD organs, but a gold standard to determine suitability for transplantation is lacking. This study aimed to incorporate individualized and predictive measurements of the liver maximum capacity (LiMAx) test to objectively grade liver function during aNRP and prevent post-op complications. Methods: aNRP was performed to salvage 18 DCD liver grafts, otherwise discarded. Continuous variables were presented as the median with the interquartile range. Results: The liver function maximum capacity (LiMAx) test was successfully performed within the aNRP circuit in 17 aNRPs (94%). Donor livers with good lactate clearance during aNRP demonstrated significantly higher LiMAx scores (396 (301-451) µg/kg/h versus those who did not 105 (70-158) µg/kg/h; P = 0.006). This was also true for manifesting stress hyperglycemia > 20 mmol/l (P = 0.032). LiMAx score correlated with alanine aminotransferase (ALT; R = - 0.755) and aspartate transaminase (AST; R = - 0.800) levels during perfusion and distinguished livers that were selected for transplantation (397 (346-453) µg/kg/h) from those who were discarded (155 (87-206) µg/kg/h; P < 0.001). Twelve livers were accepted for transplantation, blinded for LiMAx results, and all had LiMAx scores of > 241 µg/kg/h. Postoperatively, LiMAx during aNRP displayed correlation with 24-h lactate levels. Conclusions: This study shows for the first time the feasibility to assess liver function during aNRP in individual donor livers. LiMAx presents an objective tool to predict donor liver function and risk of complications in the recipient, thus enabling individualized matching of donor livers for an individual recipient. The LiMAx test may present a valuable test for the prediction of donor liver function, preventing post-transplant complication, and personalizing the selection of donor livers for individual recipients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00371-7.

Procurement Trends, Indications, and Outcomes of Heart-Lung Transplantation in the Contemporary Era.

BACKGROUND: Evolving trends in organ procurement and technological innovation prompted an investigation into recent trends, indications, and outcomes following combined heart-lung transplantation (HLTx). METHODS: The United Network for Organ Sharing database was queried for all adult (≥18 years) HLTx performed between July 1, 2013 and June 30, 2023. Patients with previous transplants were excluded. The primary endpoint was the effect of donor, recipient, and transplantation characteristics on 1- and 5-year survival. Secondary analyses included a comparison of HLTx at high- and low-volume centers, an assessment of HLTx following donation after circulatory death (DCD), and an evaluation of HLTx volume over time. Cox proportional-hazards models were used to assess factors associated with mortality. Temporal trends were evaluated with linear regression. RESULTS: After exclusions, 319 patients were analyzed, of whom 5 (1.6%) were DCD. HLTx volume increased from 2013 to 2023 (p < 0.001). One- and 5-year survival following HLTx was 84.0% and 59.5%, respectively. One-year survival was higher for patients undergoing HLTx at a high-volume center (88.3% vs. 77.9%; p = 0.012). After risk adjustment, extracorporeal membrane oxygenation support 72 h posttransplant and predischarge dialysis were associated with increased 1-year mortality (HR = 3.19, 95% CI = 1.86-5.49 and HR = 3.47, 95% CI = 2.17-5.54, respectively) and 5-year mortality (HR = 2.901, 95% CI = 1.679-5.011 and HR = 3.327, 95% CI = 2.085-5.311, respectively), but HLTx at a high-volume center was not associated with either. CONCLUSIONS: HLTx volume has resurged, with DCD HLTx emerging as a viable procurement strategy. Factors associated with 1- and 5-year survival may be used to guide postoperative management following HLTx.

Donation After Circulatory Death following Withdrawal of Life-Sustaining Treatments. Are We Ready to Break the Dead Donor Rule?

A fundamental criterion considered essential to deem the procedure of vital organ procurement for transplantation ethical is that the donor must be dead, as per the Dead Donor Rule (DDR). In the case of Donation after Circulatory Death (DCD), is the donor genuinely dead? The main aim of this article is to clarify this uncertainty, which primarily arises from the fact that in DCD, death is determined based on cardiac criteria (Circulatory Death, CD), rather than neurological criteria (Brain Death, BD), and that to allow the procurement procedure, physicians reperfuse the organs in an assisted manner. To ensure that the cessation of circulation leads to the irreversible loss of brain functions, DCD regulations require that physicians wait a certain period after CD before commencing vital organ procurement. However, during this "no-touch period," the organs are at risk of damage, potentially rendering them unsuitable for transplantation. When DCD is performed on patients whose CD follows a Withdrawal of Life-Sustaining Treatment (WLST) (DCD Maastricht III category), how long should the no-touch period last? Does its existence really make sense? Does beginning the procedure of vital organ procurement immediately after WLST constitute a violation of the DDR that can be ethically justified? The discussion aims to provide arguments in support of the non-absoluteness of the DDR.

The current landscape of in situ and ex-situ machine perfusion utilization for liver grafts from cardiac donation after circulatory death donors in the US.

Donation after circulatory death (DCD) is driving the increase in deceased organ donors in the United States. Normothermic regional perfusion (NRP) and ex-situ machine perfusion (es-MP) have been instrumental in improving liver transplant outcomes and graft utilization. This study examines the current landscape of liver utilization from cardiac DCD donors in the US. Using the UNOS STAR file, all adult (≥ 18 years old) DCD donors in the US in which the heart was used for transplantation from October 1, 2020, to September 30, 2023, were compared using procurement technique (NRP versus super rapid recovery [SRR]) and storage strategy (es-MP versus static cold storage [SCS]). 188 livers were transplanted from 309 TA-NRP donors (61% utilization) versus 305 (56%) liver transplants from 544 SRR donors. Es-MP was used in 20% (n= 38) of NRP cases versus 32% (98) of SRR cases. 281 (59%) of liver grafts were exposed to NRP, es-MP, or both. While there is widespread utilization of machine perfusion, more research is needed to determine optimal graft management strategies, particularly concerning the use of multiple technologies in complementary ways. More complete data collection is necessary at a national level to address these important research questions.

Protective effects of mesenchymal stem cells-derived extracellular vesicles against ischemia-reperfusion injury of hearts donated after circulatory death: Preliminary study in a pig model.

INTRODUCTION: Insufficient supply of cardiac grafts represents a severe obstacle in heart transplantation. Donation after Circulatory Death (DCD), in addition to conventional donation after brain death, is one promising option to overcome the organ shortage. However, DCD organs undergo an inevitable more extended period of warm unprotected ischemia between circulatory arrest and graft procurement. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have shown remarkable protective effects against ischemia-reperfusion injury. Thus, we aimed to enhance grafts preservation from DCD donors, through treatment with MSC-EVs. METHODS: Female pigs were euthanized by barbiturate overdose and after 20 min of a flat EKG, the chest was opened, the heart harvested and subsequently connected to an extracorporeal perfusion machine. MSC-EVs, isolated by ion exchange chromatography, were added to the perfusion solution (1×1011 particles) and the heart was perfused for 2 h. Then, heart tissue biopsies were taken to assess histological changes, mitochondrial morphology, antioxidant enzyme activity and inflammation mediators' expression. Biochemical parameters of myocardial viability were assessed in the perfusate. RESULTS: The treatment with MSC-EVs significantly prevented mitochondria swelling, mitochondrial cristae loss and oxidative stress in cardiac tissue. The protective effect of MSC-EVs was confirmed by the delayed increase of the cardiac-specific enzymes CK and TnC in the perfusate and the reduction of caspase-3+ cells in tissue sections. CONCLUSION: MSC-EVs improve graft quality by preserving the mitochondrial ultrastructure protecting the myocardium against oxidative stress, reducing apoptosis of cardiac cells and preventing the increase of pro-inflammatory cytokines.

Tuscany Normothermic Regional Perfusion Mobile Teams for Controlled Donation After Circulatory Death.

INTRODUCTION: 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, some countries have launched a local cDCD network with an ECMO mobile team for normothermic regional perfusion (NRP). In the Tuscany region, in 2021, the Regional Transplant Authority launched a cDCD program to make the cDCD pathway feasible even in peripheral hospitals with NRP mobile teams, which were "converted" existing ECMO mobile teams, composed of highly skilled and experienced personnel. METHODS: We describe the Tuscany cDCD program, (2021-2023), for cDCD from peripheral hospitals with NRP mobile teams. RESULTS: Twenty-six cDCDs (26/40, 65%) came from peripheral hospitals. Following the launch of the cDCD program, cDCDs from peripheral hospitals increased, from 33% (2021) to 75% (2022 and 2023) of the overall cDCDs. The mean age was 63 years, with older donors (>75 years) in half the cases. The median warm ischemia time was 45 min (20 min are required by the Italian law for death certification), ranging from 35 to 59 min. Among the 20 livers retrieved and 18 kidneys retrieved, 16 livers, and 11 kidneys (single kidney transplantation) were transplanted, after ex vivo reperfusion, respectively. CONCLUSIONS: The use of NRP mobile teams proved to be feasible and safe in the management of cDCD in peripheral hospitals. No complications were reported with NRP despite the advanced age of most cDCDs.

Impact of Warm Ischemia Time on Donation After Circulatory Death Kidney Transplant Outcomes.

BACKGROUND: Efforts to address the shortage of donor organs include increasing the use of renal allografts from donors after circulatory death (DCD). While warm ischemia time (WIT) is thought to be an important factor in DCD kidney evaluation, few studies have compared the relationship between WIT and DCD kidney outcomes, and WIT acceptance practices remain variable. METHODS: We conducted a single-center retrospective review of all adult patients who underwent deceased donor kidney transplantation from 2000 to 2021. We evaluated the impact of varied functional warm ischemia time (fWIT) in controlled DCD donors by comparing donor and recipient characteristics and posttransplant outcomes between high fWIT (>60 min), low fWIT (≤60 min), and kidneys transplanted from donors after brain death (DBD). RESULTS: Two thousand eight hundred eleven patients were identified, 638 received low fWIT DCD, 93 received high fWIT DCD, and 2080 received DBD kidneys. There was no significant difference in 5-year graft survival between the DCD low fWIT, high fWIT, and DBD groups, with 84%, 83%, and 83% of grafts functioning, respectively. Five-year patient survival was 91% in the low fWIT group, 92% in the high fWIT group, and 90% in the DBD group. An increase in kidney donor risk index (KDRI) (HR 3.37, 95% CI = 2.1-5.7) and high CIT compared to low CIT (HR 2.12, 95% CI = 1.4-3.1) have higher hazard ratios for 1-year graft failure. CONCLUSIONS: Increased acceptance of kidneys from selected DCD donors with prolonged fWIT may present an opportunity to increase kidney utilization while preserving outcomes. Our group specifically prioritizes the use of kidneys from younger donors, with lower KDPI, and without acute kidney injury, or risk factors for underlying chronic kidney disease.

Early U.S. Heart Transplant Experience With Normothermic Regional Perfusion Following Donation After Circulatory Death.

BACKGROUND: Heart transplantation following donation after circulatory death (DCD HT) has short-term survival outcomes comparable to donation after brain death and has led to a significant increase in transplantation volume. The U.S. experience with the normothermic regional perfusion (NRP) DCD HT procurement method has not been evaluated. OBJECTIVES: The aim of this study was to examine short-term outcomes associated with NRP vs direct procurement and perfusion (DPP) methods used during DCD HT in the United States. METHODS: The UNOS (United Network for Organ Sharing) registry was queried for all adult (age ≥18 years) heart recipients and corresponding donors of controlled DCD HT from January 2019-December 2023. Transplantations were stratified by NRP or DPP reperfusion methods. The primary outcome was overall survival. RESULTS: A total of 918 heart donors and recipients met inclusion criteria, including 622 (68%) DPP and 296 (32%) NRP transplantations. Unadjusted Kaplan-Meier survival analysis demonstrated improved short-term survival associated with NRP (log-rank P = 0.005). After adjustment, DCD HT with NRP was independently associated with improved survival (HR: 0.39 [95% CI: 0.22-0.70]; P = 0.002). A propensity-matched analysis similarly demonstrated a cumulative survival benefit to NRP (log-rank P = 0.006). CONCLUSIONS: In this largest national series of DCD HT procurement perfusion strategies, NRP is associated with improved short-term survival as compared with DPP. This study evaluates the U.S. early experience with DCD HT, and longer-term follow-up data are needed to further assess the impact of DPP and NRP methods on post-heart transplantation outcomes.

Revolutionizing Donor Heart Procurement: Innovations and Future Directions for Enhanced Transplantation Outcomes.

Heart failure persists as a critical public health challenge, with heart transplantation esteemed as the optimal treatment for patients with end-stage heart failure. However, the limited availability of donor hearts presents a major obstacle to meeting patient needs. In recent years, the most groundbreaking progress in heart transplantation has been in donor heart procurement, significantly expanding the donor pool and enhancing clinical outcomes. This review comprehensively examines these advancements, including the resurgence of heart donation after circulatory death and innovative recovery and evaluation technologies such as normothermic machine perfusion and thoraco-abdominal normothermic regional perfusion. Additionally, novel preservation methods, including controlled hypothermic preservation and hypothermic oxygenated perfusion, are evaluated. The review also explores the use of extended-criteria donors, post-cardiopulmonary resuscitation donors, and high-risk donors, all contributing to increased donor availability without compromising outcomes. Future directions, such as xenotransplantation, biomarkers, and artificial intelligence in donor heart evaluation and procurement, are discussed. These innovations promise to address current limitations and optimize donor heart utilization, ultimately enhancing transplantation success. By identifying recent advancements and proposing future research directions, this review aims to provide insights into advancing heart transplantation and improving patient outcomes.

Swedish Intensive Care Nurses' Knowledge, Attitudes, and Views on Donation After Circulatory Death Before a National Implementation.

Introduction: An increasing population and a shortage of identified potential organ donors are causing the waiting list for organ transplants to grow continuously. Donation after circulatory death (DCD) is a method aimed at meeting the demand for transplantable organs. However, it presents new challenges in nursing care, and there is a lack of studies investigating nurses' attitudes and knowledge of DCD. Objective: The objective of this study was to determine and describe intensive care nurses' (ICNs') knowledge, attitudes, and views on DCD before a national implementation in Sweden. Method: This study utilized a cross-sectional mixed-method design. A convenience sampling method was employed, targeting ICNs working in four intensive care units in Sweden. A study-specific tool comprising fixed and free-text questions was developed. Fifty-one ICNs participated. Data were analyzed descriptively, and correlation analysis was performed using Spearman's correlation. Free-text answers were qualitatively assessed and analyzed. An integrated analysis was conducted to synthesize the quantitative and qualitative findings. Results: Fifty-three percent reported limited knowledge about DCD. Nurses with previous education on DCD had significantly higher knowledge (r = .380, p = .006), were more engaged with the public debate on organ donation (r = .423, p = .002), and considered the ethical aspects of DCD more thoroughly (r = .386, p = .022). The qualitative analysis identified four key categories: The importance of the team, the need for ethical discussions, increased knowledge of DCD, and unanswered questions and unmet needs. The integrated analysis underscored the need for targeted education, clear guidelines, and ongoing ethical discussions to prepare ICU nurses for DCD. Conclusion: Nurses educated in organ donor care had better knowledge and a more positive attitude toward DCD implementation. The study also highlights the importance of interprofessional teamwork in DCD implementation. The findings suggest that education on DCD could improve the identification and implementation of DCD donors, addressing the global shortage of transplantable organs.

Air-ventilated normothermic mechanical perfusion improves susceptibility to donation after circulatory death and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis.

End-ischemic normothermic mechanical perfusion (NMP) could provide a curative treatment to reduce cholestatic liver injury from donation after circulatory death (DCD) in donors. However, the underlying mechanism remains elusive. Our previous study demonstrated that air-ventilated NMP could improve functional recovery of DCD in a preclinical NMP rat model. Here, metabolomics analysis revealed that air-ventilated NMP alleviated DCD- and cold preservation-induced cholestatic liver injury, as shown by the elevated release of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and γ-glutamyl transferase (GGT) in the perfusate (p < .05) and the reduction in the levels of bile acid metabolites, including ω-muricholic acid, glycohyodeoxycholic acid, glycocholic acid, and glycochenodeoxycholate (GCDC) in the perfused livers (p < .05). In addition, the expression of the key bile acid metabolism enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is predominantly expressed in hepatocytes, was substantially elevated in the DCD rat liver, followed by air-ventilated NMP (p < .05), and in vitro, this increase was induced by decreased GCDC and hypoxia-reoxygenation in the hepatic cells HepG2 and L02 (p < .05). Knockdown of UGT1A1 in hepatic cells by siRNA aggravated hepatic injury caused by GCDC and hypoxia-reoxygenation, as indicated by the ALT and AST levels in the supernatant. Mechanistically, UGT1A1 is transcriptionally regulated by peroxisome proliferator-activator receptor-γ (PPAR-γ) under hypoxia-physoxia. Taken together, our data revealed that air-ventilated NMP could alleviate DCD- and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis. Based on the results from this study, air-ventilated NMP confers a promising approach for predicting and alleviating cholestatic liver injury through PPAR-γ/UGT1A1 axis.

Identification of the Anti-ischemia-reperfusion Injury Effect of Baicalein from Scutellaria Baicalensis Georgi in Liver Transplantation.

BACKGROUND: The complex etiology of Ischemia-Reperfusion Injury (IRI) induced by liver transplantation (LT) and the "one-target-focused" method limit the development of effective therapeutic interventions. We aimed to reveal the specific active ingredients and mechanisms involved in the Chinese herb Scutellaria baicalensis Georgi (SBG) in alleviating IRI in LT. METHODS: The active ingredients and potential macromolecular targets of SBG were screened through related databases. The differentially expressed genes of LT were obtained from GSE151648. The protein-protein interaction network was constructed by the STRING database, and Cytoscape 3.7.1 was used to construct a compound-target-disease network. GO and KEGG enrichment analyses were performed on the DAVID database. Finally, the main active components of SBG and the corresponding mechanisms were verified in a donation after circulatory death (DCD) rat LT model. RESULTS: Thirty-two active ingredients of SBG and their targets were identified, and a total of 38 intersection targets were obtained. GO function and KEGG pathway enrichment analyses demonstrated that the plasma membrane and its components play an important role. Molecular docking showed baicalein, the core component of SBG, had a strong binding ability to all hub targets. Next, in DCD rats, baicalein was proven to improve liver function, alleviate pathological injury and apoptosis, and increase the survival rate. Baicalein also significantly affected the expression of 7 hub genes. Furthermore, baicalein could inhibit ferroptosis by inhibiting phospholipid peroxidation. CONCLUSION: Baicalein, the main component of SBG, could alleviate IRI, affect the expression of hub genes, and inhibit ferroptosis in LT.

Ex Situ Left Ventricular Pressure-Volume Loop Analyses for Donor Hearts: Proof of Concept in an Ovine Experimental Model.

Ex situ heart perfusion (ESHP) has emerged as an important strategy to preserve donation after brain death (DBD) and donation after circulatory death (DCD) donor hearts. Clinically, both DBD and DCD hearts are successfully preserved using ESHP. Viability assessment is currently based on biochemical values, while a reliable method for graft function assessment in a physiologic working mode is unavailable. As functional assessment during ESHP has demonstrated the highest predictive value of outcome post-transplantation, this is an important area for improvement. In this study, a novel method for ex situ assessment of left ventricular function with pressure-volume loop analyses is evaluated. Ovine hearts were functionally evaluated during normothermic ESHP with the novel pressure-volume loop system. This system provides an afterload and adjustable preload to the left ventricle. By increasing the preload and measuring end-systolic elastance, the system could successfully assess the left ventricular function. End-systolic elastance at 60 min and 120 min was 2.8 ± 1.8 mmHg/mL and 2.7 ± 0.7 mmHg/mL, respectively. In this study we show a novel method for functional graft assessment with ex situ pressure-loop analyses during ESHP. When further validated, this method for pressure-volume assessments, could be used for better graft selection in both DBD and DCD donor hearts.