Search

IntroductionPatients with cirrhosis undergoing liver transplantation frequently exhibit systemic inflammation, coagulation derangements, and edema, indicating endothelial dysfunction. This syndrome may worsen after ischemia-reperfusion injury of the liver graft, coincident with organ dysfunction that worsens patient outcomes. Little is known about changes in endothelial permeability during liver transplantation. We hypothesized that sera from these patients would increase permeability in cultured human endothelial cells ex vivo.MethodsAdults with cirrhosis presenting for liver transplantation provided consent for blood collection during surgery. Sera were prepared at five time points spanning the entire operation. The barrier function of human pulmonary microvascular endothelial cells in culture was assessed by transendothelial resistance measured using the ECIS ZΘ system. Confluent cells from two different endothelial cell donors were stimulated with human serum from liver transplant patients. Pooled serum from healthy men and purified inflammatory agonists served as controls. The permeability response to serum was quantified as the area under the normalized resistance curve. Responses were compared between time points and analyzed for associations with clinical characteristics of liver transplant patients and their grafts.ResultsLiver transplant sera from all time points during surgery-induced permeability in both endothelial cell lines. The magnitude of permeability change was heterogeneous between patients, and there were differences in the effects of sera on the two endothelial cell lines. In one of the cell lines, the severity of liver disease was associated with greater permeability at the start of surgery. In the same cell line, serum collected 15 min after liver reperfusion induced significantly more permeability as compared to that collected at the start of surgery. Early postreperfusion sera from patients undergoing living donor transplants induced more permeability than sera from deceased donor transplants. Sera from two exemplary cases of patients on preoperative dialysis, and one patient with an unexpectedly long warm ischemia time of the liver graft, induced exaggerated and prolonged endothelial permeability.DiscussionSerum from patients with cirrhosis undergoing liver transplantation induces permeability of cultured human pulmonary microvascular endothelial cells. Increased endothelial permeability during liver transplantation may contribute to organ injury and present a target for future therapeutics.

Background Methods Results Conclusions Liver transplantation (LT) is still limited by organ shortage and post‐transplant monitoring issues. While machine perfusion techniques allow for improving organ preservation, biomarkers like donor‐derived cell‐free DNA (dd‐cfDNA) and mitochondrial cfDNA (mt‐cfDNA) may provide insights into graft injury and viability pre‐ and post‐LT.A prospective observational cohort study was conducted on LT recipients (n = 45) to evaluate dd‐cfDNA as a biomarker of graft dysfunction during the first 6 months after LT. Dd‐cfDNA was quantified on blood samples collected pre‐LT and post‐LT using droplet digital PCR. In livers undergoing dual hypothermic oxygenated machine perfusion (D‐HOPE), total cfDNA and mt‐cfDNA levels were measured on perfusate samples collected at 30‐min intervals. Correlations with graft function and clinical outcomes were assessed.Dd‐cfDNA levels peaked post‐LT and correlated with transaminase levels and histological injury severity. The longitudinal assessment showed that postoperative complications and rejection were associated with an increase in dd‐cfDNA levels. Mt‐cfDNA levels in D‐HOPE perfusate correlated with graft function parameters post‐LT and were higher in patients with early allograft dysfunction and severe complications.This study confirms dd‐cfDNA as a marker of graft injury after LT and suggests that perfusate mt‐cfDNA levels during D‐HOPE correlate with graft function and post‐transplant clinical outcome. Integration of these tests into clinical practice may improve transplant management and viability assessment during hypothermic perfusion. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have explored the effects of L-arginine, whether administered in the form of a supplement or through infusion during cardioplegia, on cardiac and inflammatory markers in individuals undergoing coronary artery bypass grafting (CABG). However, these studies presented contradictory findings. Consequently, the objective of this study was to investigate the impact of l-arginine on these markers by analyzing available randomized controlled trials (RCTs). Methods: We performed an extensive search across various databases, including Embase, Medline/PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar, covering research published until December 2023. To analyze the mean changes in inflammatory and cardiac markers between the L-arginine and control groups, we calculated the weighted mean difference (WMD) along with the corresponding 95% confidence interval (CI) using a random-effects model. Results: A total of 393 RCTs were identified during the initial search. After screening and selection, 7 trials were included. In a meta-analysis of three trials that reported troponin T levels, we found a significant impact of L-arginine on reducing troponin T levels (WMD = -0.61 ng/ml; 95% CI: -1.07, -0.15). Our analysis also showed that L-arginine had a noticeable impact on decreasing interleukin-6 (IL-6) levels (WMD = -7.72 pg/ml; 95% CI: -15.05, -0.39). However, we found no considerable impact of L-arginine treatment on creatine phosphokinase-MB (CPK-MB), tumor necrosis factor-alpha (TNF-α), and troponin I compared to the placebo groups. Conclusions: Our findings suggest that L-arginine may benefit patients undergoing CABG, as it helps reduce inflammatory reactions and limits myocardial ischemia. This study registered in the PROSPERO database (Registration No. CRD42024508341). [ABSTRACT FROM AUTHOR]

Liver transplantation has evolved into a mature clinical field, but scarcity of usable organs poses a unique challenge. Expanding the donor pool requires novel approaches for protecting hepatic physiology and cellular homeostasis. Here we define hepatocellular injury during transplantation, with an emphasis on modifiable cell death pathways as future therapeutics. [ABSTRACT FROM AUTHOR]

Objective To explore the role and mechanism of tannic acid in renal ischemia-reperfusion injury (IRI) in mice. Methods Male C57BL/6J mice were randomly divided into sham operation group (Sham group), blank control group (Sham+TA group), experimental group (IRI group) and treatment group (IRI+TA group), with 20 mice in each group. The survival of mice after renal IRI was observed 48 h after surgery. Serum and renal tissue samples were collected from mice 24 h after IRI (5 mice per group), and the levels of blood urea nitrogen and serum creatinine were detected. The levels of inflammatory factors and ferroptosis-related indicators in renal tissue were detected. The pathological damage of renal tissue was assessed. The protein expression levels of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase longchain family 4 (ACSL4) in renal tissue were detected. Molecular docking software was used to explore the binding activity of tannic acid with nuclear factor E2-related factor 2 (Nrf2) and to verify the expression of Nrf2 and heme oxygenase-1 (HO-1). Results Compared with the IRI group, the postoperative survival rate of mice in the IRI+TA group was higher (0 vs. 60%), the levels of serum creatinine and blood urea nitrogen were decreased, the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in renal tissue were decreased, the renal tissue injury was improved, the levels of malondialdehyde and ferrous ions in renal tissue were reduced, the level of glutathione was increased, the expression of GPX4 was increased, and the expression of ACSL4 was decreased (all P<0.05). Tannic acid may form a suitable spatial complement with Nrf2, with a binding energy of −8.7 kcal/mol, indicating a strong binding ability of tannic acid with Nrf2. The protein levels of Nrf2 and HO-1 in the renal tissue of mice in the IRI+TA group were upregulated. Conclusions Tannic acid may bind to Nrf2 protein, activate the Nrf2/HO-1 pathway to inhibit ferroptosis, and alleviate renal IRI in mice. [ABSTRACT FROM AUTHOR]

Objective To explore the effect and mechanism of microRNA (miR)-155-5p on myocardial pyroptosis in rats with myocardial ischemia-reperfusion injury (IRI). Methods Sixty SD rats were randomly divided into sham group, IRI group, agomir-NC group, miR-155-5p agomir group, antagomir-NC group, and miR-155-5p antagomir group, with 10 rats in each group. Echocardiography was used to measure the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) of rats. Enzyme-linked immune absorbent assay (ELISA) was used to detect the levels of creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin T (cTnT) in serum, as well as the levels of interleukin (IL)-1β, IL-6, IL-18, and tumor necrosis factor (TNF)-α in myocardial tissue of rats. Hematoxylin-eosin staining was used to observe pathological changes in rat myocardial tissue. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of miR-155-5p and silent information regulator 1 (SIRT1) messenger RNA (mRNA) in myocardial tissue of rats. Dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-155-5p and SIRT1. Western blot was used to detect the expression levels of SIRT1, NOD-like receptor protein 3 (NLRP3), cleaved cysteine aspartate specific proteinase-1 (Cleaved Caspase-1), and gasdermin D (GSDMD) proteins in myocardial tissue of rats. Results Compared with the sham group, the LVEDD and LVESD of rats in the IRI group were increased, LVEF and LVFS were decreased, serum levels of CK-MB, LDH, and cTnT were increased, IL-1β, IL-6, IL-18 and TNF-α levels in myocardial tissue were increased, myocardial tissue structure was severely damaged, myocardial fibers were disordered, relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased, and the relative expression of SIRT1 protein was decreased (all P<0.05/5). Compared with the IRI group, the rats in the miR-155-5p agomir group had increased LVEDD and LVESD, decreased LVEF and LVFS, increased serum levels of CK-MB, LDH, and cTnT, increased myocardial tissue levels of IL-1β, IL-6, IL-18, TNF-α, aggravated myocardial tissue lesions, increased relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins, and decreased relative expression of SIRT1 protein, and the rats in the miR-155-5p antagomir group had decreased LVEDD and LVESD, increased LVEF and LVFS, decreased serum levels of CK-MB, LDH, and cTnT, decreased myocardial tissue levels of IL-1β, IL-6, IL-18, TNF-α, reduced myocardial tissue lesions, decreased relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins, and increased relative expression of SIRT1 protein (all P<0.05/5). miR-155-5p was negatively correlated with the expression levels of SIRT1 in rat myocardial tissue, and SIRT1 was a target gene of miR-155-5p. Conclusions miR-155-5p may participate in the regulation of myocardial IRI in rats by targeting the downregulation of SIRT1 and promoting NLRP3-mediated myocardial pyroptosis. [ABSTRACT FROM AUTHOR]

Objective To investigate the role and mechanism of silent information regulator 1 (SIRT1)-NOD-like receptor protein 3 (NLRP3) axis in the effect of remifentanil against ischemia-reperfusion injury (IRI) in rat livers. SD rats were randomly divided into sham operation group (sham group), IRI group, IRI+remifentanil pretreatment group (IRI+RPC group), IRI+SIRT1 inhibitor EX-527 group (IRI+EX-527 group) and IRI+RPC+EX-527 group, with 8 rats in each group. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), interleukin (IL)-1β and IL-18 of rats in each group were detected. The liver tissue pathology was observed. The apoptosis rate of hepatocytes in rats was detected. The expressions of SIRT1, NLRP3, cleaved cysteinyl aspartate specific proteinase-1 (Cleaved Caspase-1) and Gasdermin D (GSDMD) proteins in rat liver tissue were detected. Results Compared with the sham group, the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI group were increased, the serum ALT, AST, LDH, IL-1β, and IL-18 levels were increased, the relative expression of SIRT1 protein in liver tissue was decreased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased (all P<0.05). Compared with the IRI group, the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+RPC group were decreased, the serum ALT, AST, LDH, IL-1β, and IL-18 levels were decreased, the relative expression of SIRT1 protein in liver tissue was increased, and the relative expression of NLRP3, Cleaved Caspase1, and GSDMD proteins were decreased; the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+EX-527 group were increased, the ALT, AST, LDH, IL-1β, and IL-18 levels were increased, the relative expression of SIRT1 protein in liver tissue was decreased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased (all P<0.05). Compared with the IRI+RPC group, the liver tissue pathological score and hepatocyte apoptosis rate in the IRI+RPC+EX-527 group were increased, the levels of ALT, AST, LDH, IL-1β, and IL-18 were increased, the relative expression of SIRT1 protein in liver tissue was decreased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased (all P<0.05). Conclusions SIRT1 may participate in the regulation of remifentanil against rat liver IRI by inhibiting NLRP3 mediated cell pyroptosis. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum stress refers to a cellular stress response triggered when cells are stimulated, which is manifested as the disruption of endoplasmic reticulum homeostasis and dysfunction in various pathological conditions, resulting in the accumulation of a large number of misfolded and unfolded proteins within the endoplasmic reticulum and an imbalance of calcium ions. Macrophages are the most abundant immune cells in the liver and play an important role in maintaining liver homeostasis and various liver diseases. Recent studies have confirmed that the unfolded protein response caused by endoplasmic reticulum stress plays an important role in regulating macrophage immune response. This article reviews the mechanisms of endoplasmic reticulum stress regulating macrophage immune response and its role in liver diseases such as ischemia-reperfusion injury during organ transplantation, liver fibrosis, and hepatocellular carcinoma, in order to deepen the understanding of the mechanism of macrophage immune regulation and provide new ideas for research and interventional treatment related to liver diseases. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury (IRI) and rejection are the main factors affecting the long-term survival of transplant kidneys. IRI or rejection reactions can cause endoplasmic reticulum stress (ERS) leading to renal injury. X-box binding protein 1 (XBP1), as the main ERS-related protein regulating cell homeostasis, generates spliced XBP1 after splicing introns by inositol-requiring enzyme 1α (IRE1α), thereby affecting the expression of target genes and reshaping the cell environment. Appropriate ERS can promote cell survival. However, when the threshold is exceeded, excessive expression of XBP1 can lead to cell instability or death, thereby causing an imbalance in the renal internal environment, which is related to the pathogenesis and progression of kidney transplant-related injury. Therefore, the effective activation of XBP1 has a protective effect on stress injury and helps maintain the vitality and integrity of the renal system. This article reviews the ERS pathway IRE1α-XBP1, the role of XBP1 in renal parenchymal cells and immune cells, the role of XBP1 in renal ischemic injury and rejection, and the clinical detection and potential therapies targeting XBP1. It explores the potential value of targeting XBP1 in kidney transplant-related injury, aiming to provide new targets and directions for improving the prognosis of kidney transplantation. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion (I/R) injury with severe cell death is a major complication involved in liver transplantation and resection. The identification of key regulators improving hepatocyte activity may provide potential strategies to clinically resolve I/R-induced injury. N6-methyladenosine (m6A) RNA modification is essential for tissue homeostasis and pathogenesis. However, the potential involvement of m6A in the regulation of hepatocyte activity and liver injury has not been fully explored. In the present study, we found that hepatocyte AlkB homolog H5 (ALKBH5) levels were decreased both in vivo and in vitro I/R models. Hepatocyte-specific ALKBH5 overexpression effectively attenuated I/R-induced liver necrosis and improved cell proliferation in mice. Mechanistically, ALKBH5-mediated m6A demethylation improved the mRNA stability of YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1), thereby increasing its expression, which consequently promoted the translation of Yes-associated protein (YAP). In conclusion, ALKBH5 is a regulator of hepatic I/R injury that improves hepatocyte repair and proliferation by maintaining YTHDF1 stability and YAP content. The ALKBH5–m6A–YTHDF1–YAP axis represents promising therapeutic targets for hepatic I/R injury to improve the prognosis of liver surgery. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary ischemia-reperfusion (IR) injury (IRI) plays a significant role in various lung disorders and is a key factor in the development of primary graft dysfunction following lung transplantation. Hemopexin (Hx) is the major serum scavenger protein for heme, which is a prooxidant and pro-inflammatory compound. In the current study, we hypothesized that Hx could confer beneficial effects in sterile inflammation induced by IR-mediated lung injury. Methods: To examine this hypothesis, we administered Hx in an experimental mouse model of unilateral lung IRI. Results: Our results demonstrate that treatment with Hx alleviated histopathological signs of inflammation in ischemic lungs, as evidenced by a reduction in the number of infiltrating neutrophils and decreased levels of perivascular edema. In addition, thrombotic vaso-occlusion in pulmonary blood vessels of IRI lungs was reduced by Hx. Immunohistochemical analysis revealed that Hx inhibited the up-regulation of heme oxygenase-1, an enzyme highly induced by heme, in ischemic lungs. Finally, Hx administration caused a decrease in the levels of circulating B- and CD8+ T-lymphocytes in the peripheral blood of mice with pulmonary IRI. Conclusion: These findings suggest that the serum heme scavenger protein Hx holds therapeutic promise in alleviating lung IRI-mediated sterile inflammation. Thus, Hx may represent a preemptive therapeutic approach in IR-related lung disorders such as primary graft dysfunction in lung transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary ischemia-reperfusion (IR) injury (IRI) plays a significant role in various lung disorders and is a key factor in the development of primary graft dysfunction following lung transplantation. Hemopexin (Hx) is the major serum scavenger protein for heme, which is a prooxidant and pro-inflammatory compound. In the current study, we hypothesized that Hx could confer beneficial effects in sterile inflammation induced by IR-mediated lung injury. Methods: To examine this hypothesis, we administered Hx in an experimental mouse model of unilateral lung IRI. Results: Our results demonstrate that treatment with Hx alleviated histopathological signs of inflammation in ischemic lungs, as evidenced by a reduction in the number of infiltrating neutrophils and decreased levels of perivascular edema. In addition, thrombotic vaso-occlusion in pulmonary blood vessels of IRI lungs was reduced by Hx. Immunohistochemical analysis revealed that Hx inhibited the up-regulation of heme oxygenase-1, an enzyme highly induced by heme, in ischemic lungs. Finally, Hx administration caused a decrease in the levels of circulating B- and CD8+ T-lymphocytes in the peripheral blood of mice with pulmonary IRI. Conclusion: These findings suggest that the serum heme scavenger protein Hx holds therapeutic promise in alleviating lung IRI-mediated sterile inflammation. Thus, Hx may represent a preemptive therapeutic approach in IR-related lung disorders such as primary graft dysfunction in lung transplantation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the mechanism of Klotho protein on myocardial ischemia-reperfusion injury in rats. Methods: Sixty male SD rats were selected, and 60 rats were divided into normal control group, ischemia reperfusion injury + saline group, ischemia reperfusion injury + low concentration Klotho protein group, ischemia reperfusion injury + high concentration Klotho protein group, 15 in each group. Treatment was performed separately and the expression of relevant serum and protein was analyzed to contrast apoptosis. Results: The serum IL-6, IL-1B, TNF-α, NF-кВ, Іккẞ, caspase9, ROS, MDA, apoptosis: Ischemia-reperfusion injury + normal saline group ischemia-reperfusion injury + low-concentration Klotho protein group>ischemia-reperfusion injury + high-concentration Klotho protein group normal control group; Serum ІкВа, Klotho protein, Heart tissue Klotho protein, caspase3, Cytochrome C, Bax/Bcl-2 protein, ATP, diphosphate, ATP, SOD: Ischemia-reperfusion injury + normal saline group

β3-Adrenergic receptor (β3AR) agonists have been shown to protect against ischemia–reperfusion injury (IRI). Since β3ARs are present both in cardiomyocytes and in endothelial cells, the cellular compartment responsible for this protection has remained unknown. Using transgenic mice constitutively expressing the human β3AR (hβ3AR) in cardiomyocytes or in the endothelium on a genetic background of null endogenous β3AR expression, we show that only cardiomyocyte expression protects against IRI (45 min ischemia followed by reperfusion over 24 h). Infarct size was also limited after ischemia–reperfusion in mice with cardiomyocyte hβ3AR overexpression on top of endogenous β3AR expression. hβ3AR overexpression in these mice reduced IRI-induced cardiac fibrosis and improved long-term left ventricular systolic function. Cardiomyocyte-specific β3AR overexpression resulted in a baseline remodeling of the mitochondrial network, characterized by upregulated mitochondrial biogenesis and a downregulation of mitochondrial quality control (mitophagy), resulting in elevated numbers of small mitochondria with a depressed capacity for the generation of reactive oxygen species but improved capacity for ATP generation. These processes precondition cardiomyocyte mitochondria to be more resistant to IRI. Upon reperfusion, hearts with hβ3AR overexpression display a restoration in the mitochondrial quality control and a rapid activation of antioxidant responses. Strong protection against IRI was also observed in mice infected with an adeno-associated virus (AAV) encoding hβ3AR under a cardiomyocyte-specific promoter. These results confirm the translational potential of increased cardiomyocyte β3AR expression, achieved either naturally through exercise or artificially through gene therapy approaches, to precondition the cardiomyocyte mitochondrial network to withstand future insults. [ABSTRACT FROM AUTHOR]

Disturbance of the balance between production of oxygen free radicals (or some other radical species) and activity of antioxidative system of protection causes the so called oxidative stress Protection of an organism from oxygen free radicals implies activity of enzymatic (catalase, SOD, glutathione peroxidase, glutathione reductase etc.) and nonenzymatic (vitamin E. vitamin C. glutathione, uric acid etc.) systems of protection. An organism can tolerate a mild oxidative stress but a higher disturbance between the production of free radicals and the activity of the antioxidative protection results in lipid protein and DNA as well as numerous diseases. In this article we analyze oxidative stress role as an important cofactor contributing to endothelial dysfunction, inflammation, atherosclerosis, glomerulosclerosis, anemia, tubulointerstitial nephritis and ischemia-reperfusion injury to chronic kidney disease patients. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore metabolic reprogramming in diabetic myocardium subjected to ischemia–reperfusion injury (I/RI) and potential mechanisms. Background: Increased vulnerability after I/RI in diabetic myocardium is a major cause of the high prevalence of perioperative adverse cardiac events, and the specific alterations in energy metabolism after I/RI in diabetic myocardium and the impact on increased vulnerability are not fully understood. Methods: Metabolomic methods were used to explore the differences and characteristics of metabolites in the heart tissues of four groups, and then, single‐cell RNA sequencing (ScRNA‐seq) was used to explore the potential mechanism of metabolic reprogramming. Results: It was found that the fatty acid metabolism of db/db mouse I/RI (DMI) showed a significant upward trend, especially the metabolites of ultra‐long and medium‐long‐chain fatty acids; the metabolic flow analysis found that the U‐13C glucose M + 6 was significantly higher in the C57BL mouse sham operation (NM) group than in the db/db mouse sham operation (DM) group, and in the C57BL mouse I/RI (NMI) than in the DMI group. Compared with the NMI group, the intermediate metabolites of glycolysis and tricarboxylic acid (TCA) cycle were significantly reduced in the DMI group; all comparisons were statistically significant (p < 0.05), indicating that the glucose uptake of diabetic myocardetis, the ability of glucose glycolysis after I/RI, and the contribution of glucose to TCA were significantly reduced. The results of ScRNA‐seq revealed that the number of Cluster 0 myocardial isoforms was significantly increased in diabetic myocardium, and the differential genes were mainly enriched in fatty acid metabolism, and the PPARA signaling pathway was found to be over‐activated and involved in the regulation of metabolic reprogramming of diabetic myocardial I/RI. Conclusion: Metabolic reprogramming of diabetic myocardial I/RI may be the main cause of increased myocardial vulnerability. The number of myocardial subtype Cluster 0 increased significantly, and PPARA PPARA is a ligand‐activated receptor of the nuclear hormone receptor family that plays a central regulatory role in lipid metabolism. signaling pathway activation may be a potential mechanism for reprogramming metabolism in diabetic myocardium. [ABSTRACT FROM AUTHOR]

Ischemic heart disease stands as the primary cause of mortality among diabetic patients. Despite advancements in vascular reconstruction and thrombolytic therapy that restore myocardial blood flow, these patients often experience poor cardiac function recovery and a higher mortality rate. This makes myocardial ischemia/reperfusion (I/R) injury a significant therapeutic challenge. Researches indicate that, under diabetic or obese conditions, adipocytes release extracellular vesicles (EVs) containing a variety of biomolecules, including RNA, proteins, adipocytokines, and mitochondria. These EVs play a pivotal role in maintaining systemic metabolic homeostasis. Importantly, adipocyte - derived EVs facilitate communication with diabetic hearts and play a regulatory role in myocardial I/R injury. This review summarizes recent studies on the modulatory effects of adipocyte ⁃derived EVs on diabetic myocardial I/R injury, highlighting potential underlying mechanisms. [ABSTRACT FROM AUTHOR]

This comprehensive review examines the role of Fenoldopam, a selective dopamine-1 receptor agonist, in preventing and treating acute kidney injury (AKI) during cardiac surgery. AKI remains a significant complication in cardiac surgery, associated with increased morbidity, mortality, and healthcare costs. The review explores Fenoldopam's pharmacological properties, mechanism of action, and clinical applications, synthesizing evidence from randomized controlled trials, meta-analyses, and observational studies. While some studies have shown promising results in improving renal function and reducing AKI incidence, others have failed to demonstrate significant benefits. The review discusses these conflicting findings, explores potential reasons for discrepancies, and identifies areas requiring further research. It also compares Fenoldopam to other renoprotective strategies, including dopamine, diuretics, and N-acetylcysteine. The safety profile of Fenoldopam, including common side effects and contraindications, is addressed. Current guidelines and recommendations for Fenoldopam use in cardiac surgery are presented, along with a cost-effectiveness analysis. The review concludes by outlining future research directions and potential new applications of Fenoldopam in cardiac surgery. By providing a thorough overview of the current state of knowledge, this review aims to facilitate informed decision-making for clinicians and researchers while highlighting areas for future investigation. [ABSTRACT FROM AUTHOR]

Aim: Renal ischemia‐reperfusion injury (IRI) is a major cause of acute kidney injury. Hydrogen sulphide (H2S) exerts a protective effect in renal IRI. The present study was carried out to investigate the effects of exogenous H2S on renal IRI by regulating autophagy in mice. Methods: Mice were randomly assigned to control, IRI and NaHS (an H2S donor, 28, 56 and 100 μmol/kg) groups. Renal IRI was induced by clamping the bilateral renal pedicles with non‐traumatic arterial clamp for 45 min and then reperfused for 24 h. Mice were administered intraperitoneally with NaHS 20 min prior to renal ischemia. Sham group mice underwent the same procedures without clamping. Serum and kidney tissues were harvested 24 h after reperfusion for functional, histological, oxidative stress, and autophagic determination. Results: Compared with the control group, the concentrations of serum creatinine (Scr), blood urea nitrogen (BUN), and malondialdehyde (MDA), the protein levels of LC3II/I, Beclin‐1 and P62, as well as the number of autophagosomes were significantly increased, but the activity of superoxide dismutase (SOD) was decreased after renal IRI. NaHS pre‐treatment dramatically attenuated renal IRI‐induced renal dysfunction, histological changes, MDA concentration and p62 expression in a dose‐dependent manner. However, NaHS increased the SOD activity and the protein levels of LC3II/I and Beclin‐1. Conclusion: These results indicate that exogenous H2S protects the kidney from IRI through enhancement of autophagy and reduction of oxidative stress. Novel H2S donors could be developed in the treatment of renal IRI. [ABSTRACT FROM AUTHOR]

Although ischemia-reperfusion (I/R) injury varies between cortical and subcortical regions, its effects on specific regions remain unclear. In this study, we used various magnetic resonance imaging (MRI) techniques to examine the spatiotemporal dynamics of I/R injury within the salvaged ischemic penumbra (IP) and reperfused ischemic core (IC) of a rodent model, with the aim of enhancing therapeutic strategies by elucidating these dynamics. A total of 17 Sprague–Dawley rats were subjected to 1 h of transient middle cerebral artery occlusion with a suture model. MRI, including diffusion tensor imaging (DTI), T2-weighted imaging, perfusion-weighted imaging, and T1 mapping, was conducted at multiple time points for up to 5 days during the I/R phases. The spatiotemporal dynamics of blood–brain barrier (BBB) modifications were characterized through changes in T1 within the IP and IC regions and compared with mean diffusivity (MD), T2, and cerebral blood flow. During the I/R phases, the MD of the IC initially decreased, normalized after recanalization, decreased again at 24 h, and peaked on day 5. By contrast, the IP remained relatively stable. Both the IP and IC exhibited hyperperfusion, with the IP reaching its peak at 24 h, followed by resolution, whereas hyperperfusion was maintained in the IC until day 5. Despite hyperperfusion, the IP maintained an intact BBB, whereas the IC experienced persistent BBB leakage. At 24 h, the IC exhibited an increase in the T2 signal, corresponding to regions exhibiting BBB disruption at 5 days. Hyperperfusion and BBB impairment have distinct patterns in the IP and IC. Quantitative T1 mapping may serve as a supplementary tool for the early detection of malignant hyperemia accompanied by BBB leakage, aiding in precise interventions after recanalization. These findings underscore the value of MRI markers in monitoring ischemia-specific regions and customizing therapeutic strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: Compared with the use of ultrasound for noninvasive monitoring of the anesthetic sodium pentobarbital versus tribromoethanol in an animal model of renal ischemia‐reperfusion injury in rats. Methods: Adult rats were randomly assigned to a renal ischemia‐reperfusion injury model, and preoperative anesthetics were administered as either sodium pentobarbital or tribromoethanol. Color Doppler ultrasound and spectral Doppler ultrasound were used to detect changes in respiratory rate and heart rate during and after the surgery, as well as measure renal hemodynamic parameters including peak systolic velocity, end‐diastolic velocity, and resistance index. Results: The frequency of changes in respiration and heart rate was significantly higher in the sodium pentobarbital anesthesia group compared to the tribromoethanol anesthesia group. The peak systolic velocity and end‐diastolic velocity values in the sodium pentobarbital anesthesia group were significantly lower than those in the tribromoethanol group. However, the resistance index in the sodium pentobarbital group was higher than that in the tribromoethanol group. Conclusion: Ultrasound can be used to dynamically monitor the effects of anesthesia during the experiment, including changes in respiratory rate and heart rate, as well as semi‐quantitatively monitor hemodynamic changes in the kidneys, which indirectly reflects whole‐body hemodynamic changes in rats. [ABSTRACT FROM AUTHOR]

Background/Objectives: Acute mesenteric ischemia can lead to severe liver damage due to ischemia–reperfusion (I/R) injury. This study investigated the protective effects of trimetazidine (TMZ) and dexmedetomidine (DEX) against liver damage induced by mesenteric artery I/R via endoplasmic reticulum stress (ERS) mechanisms. Methods: Twenty-four rats were divided into four groups: control, I/R, I/R+TMZ, and I/R+DEX. TMZ (20 mg/kg) was administered orally for seven days, and DEX (100 µg/kg) was given intraper-itoneally 30 min before I/R induction. Liver tissues were analyzed for creatinine, alanine ami-notransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBARS), and total thiol (TT) levels. Results: Compared with the control group, the I/R group presented significantly increased AST, ALT, TBARS, and TT levels. TMZ notably reduced creatinine levels. I/R caused significant liver necrosis, inflammation, and congestion. TMZ and DEX treatments reduced this histopathological damage, with DEX resulting in a more significant reduction in infiltrative areas and vascular congestion. The increase in the expression of caspase-3, Bax, 8-OHdG, C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) decreased with the TMZ and DEX treatments. In addition, Bcl-2 positivity decreased both in the TMZ and DEX treatments. Conclusions: Both TMZ and DEX have protective effects against liver damage. These effects are likely mediated through the reduction in ERS and apoptosis, with DEX showing slightly superior protective effects compared with TMZ. [ABSTRACT FROM AUTHOR]

Ischemia‐reperfusion (I‐R) injury is the most common cause of acute kidney injury. In experiments involving primary human renal proximal tubular epithelial cells (RPTECs) exposed to anoxia‐reoxygenation, we explored the hypothesis that mitochondrial malate dehydrogenase‐2 (MDH‐2) inhibition redirects malate metabolism from the mitochondria to the cytoplasm, towards the malate‐pyruvate cycle and reversed malate‐aspartate shuttle. Colorimetry, fluorometry, and western blotting showed that MDH2 inhibition accelerates the malate‐pyruvate cycle enhancing cytoplasmic NADPH, thereby regenerating the potent antioxidant reduced glutathione. It also reversed the malate‐aspartate shuttle and potentially diminished mitochondrial reactive oxygen species (ROS) production by transferring electrons, in the form of NADH, from the mitochondria to the cytoplasm. The excessive ROS production induced by anoxia‐reoxygenation led to DNA damage and protein modification, triggering DNA damage and unfolded protein response, ultimately resulting in apoptosis and senescence. Additionally, ROS induced lipid peroxidation, which may contribute to the process of ferroptosis. Inhibiting MDH‐2 proved effective in mitigating ROS overproduction during anoxia‐reoxygenation, thereby rescuing RPTECs from death or senescence. Thus, targeting MDH‐2 holds promise as a pharmaceutical strategy against I‐R injury. [ABSTRACT FROM AUTHOR]

Background and Objectives: The majority of cardiac surgical procedures are performed using cardiopulmonary bypass and cardioplegia-induced cardiac arrest. Cardiac arrest and reperfusion may lead to ischemia-reperfusion injury of the myocardium. The aim of this study was to investigate whether gradual reperfusion with a slow increase in oxygen partial pressure leads to a reduction in reperfusion injury. Materials and Methods: Fifty patients undergoing elective cardiac surgery were included in this prospective randomized study. Patients in the hyperoxemic (control) group received conventional reoxygenation (paO2 250–300 mmHg). Patients in the normoxemic (study) group received gradual reoxygenation (1st-minute venous blood with paO2 30–40 mmHg, 2nd-minute arterial blood with paO2 100–150 mmHg). Periprocedural blood samples were taken serially, and markers of myocardial injury were analyzed. In addition, the influence of gradual reoxygenation on hemodynamics, inflammation, and the overall perioperative course was evaluated. Results: There was a trend toward higher CK levels in the hyperoxemia group without statistical significance; however, CK-MB and troponin T levels did not show any statistical difference between the two groups. Potassium concentrations in the coronary sinus were significantly higher in the hyperoxemia group at 3 and 8 min after opening of the aortic cross-clamp (6.88 ± 0.87 mmol/L vs. 6.30 ± 0.91 mmol/L and 5.87 ± 0.73 mmol/L vs. 5.43 ± 0.42 mmol/L, respectively; p = 0.03 and p = 0.02). All other measurements did not show a statistical difference between the two groups. Conclusions: The use of gradual reperfusion in cardiac surgery with cardiopulmonary bypass and cardiac arrest is safe. However, it does not reduce ischemia-reperfusion injury compared to standard hyperoxemic reperfusion. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the protective efficacy of remifentanil against testicular ischemia-reperfusion injury.The study included 24 male rats. The rats were randomized into three groups: Group 1 was the control group. Group 2 was subjected to a testicular torsion/detorsion model. Group 3 underwent similar procedures and additionally received remifentanil (0.6 μg/kg/min) intravenously for the first 20 min of reperfusion. Blood samples were taken for biochemical analyses, and orchiectomy was performed for histopathologic examination.Biochemical analysis of blood samples showed a significant increase in antioxidant enzyme activity, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in Group 3 compared to Group 2 (p:0.004 and p:0.002, respectively). There was a dramatic decrease in the levels of proinflammatory cytokines, including interleukin-1 beta (IL-1 Beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in Group 3 compared to Group 2 (p:0.001, p:0.046, and p:0.004, respectively). Similarly, malondialdehyde (MDA) levels decreased in Group 3 compared to Group 2 (p:0.004). Histopathologic examination of Group 3 rats showed positive changes in inflammation, hemorrhage, edema, and congestion levels compared to Group 2 (p<0.001). Similarly, there was a positive effect on the Johnsen and Cosentino score in Group 3 compared to Group 2 (p:0.001 and p<0.001, respectively).In our study, it has been documented that remifentanil protects against testicular ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

Background: At present, hepatic ischemia-reperfusion injury (IRI) is an important complication of partial hepatectomy and liver transplantation, and it is an important cause of poor prognosis. Spleen tyrosine kinase(SYK) plays an important role in a variety of signaling pathways in the liver, but its role in hepatic IRI is still unclear. This study aims to investigate the role and mechanism of SYK in hepatic IRI and tumor recurrence. Methods: We first observed the activation of SYK in the liver of mice in response to hepatic IRI. Subsequently, Pharmacological inhibitions of SYK were used to evaluated the effect of SYK on neutrophil recruitment and NETosis, and further explored the effect of SYK on IRI and tumor recurrence. Results: Our study shows that SYK is activated in response to hepatic IRI and aggravates liver injury. On the one hand, neutrophils SYK during the early stage of liver reperfusion increases neutrophil extracellular traps (NETs) production by promoting Pyruvate kinase M2(PKM2) nuclear translocation leading to upregulation of phosphorylated STAT3, thereby exacerbating liver inflammation and tumor recurrence. On the other hand, macrophages SYK can promote the recruitment of neutrophils and increase the activation of NLRP3 inflammasome and IL1β, which further promotes the formation of NETs. Conclusions: Our study demonstrates that neutrophil and macrophage SYK synergistically promote hepatic IRI and tumor recurrence, and SYK may be a potential target to improve postoperative hepatic IRI and tumor recurrence. [ABSTRACT FROM AUTHOR]

Ischemia‐reperfusion injury (IRI) results in irreversible metabolic dysfunction and structural damage to tissues or organs, posing a formidable challenge in the field of organ implantation, cardiothoracic surgery, and general surgery. Glycogen synthase kinase‐3β (GSK‐3β) a multifunctional serine/threonine kinase, is involved in a variety of biological processes, including cell proliferation, apoptosis, and immune response. Phosphorylation of its tyrosine 216 and serine 9 sites positively and negatively regulates the activation and inactivation of the enzyme. Significantly, inhibition or inactivation of GSK‐3β provides protection against IRI, making it a viable target for drug development. Though numerous GSK‐3β inhibitors have been identified to date, the development of therapeutic treatments remains a considerable distance away. In light of this, this review summarizes the complicated network of GSK‐3β roles in IRI. First, we provide an overview of GSK‐3β's basic background. Subsequently, we briefly review the pathological mechanisms of GSK‐3β in accelerating IRI, and highlight the latest progress of GSK‐3β in multiorgan IRI, encompassing heart, brain, kidney, liver, and intestine. Finally, we discuss the current development of GSK‐3β inhibitors in various organ IRI, offering a thorough and insightful reference for GSK‐3β as a potential target for future IRI therapy. [ABSTRACT FROM AUTHOR]

Despite resuscitation advances including extracorporeal cardiopulmonary resuscitation (ECPR), freedom from neurologic and myocardial insult after cardiac arrest remains unlikely. We hypothesized that adenosine 2A receptor (A2AR) agonism, which attenuates reperfusion injury, would improve outcomes in a porcine model of ECPR. Adult swine underwent 20 min of circulatory arrest followed by defibrillation and 6 h of ECPR. Animals were randomized to receive saline vehicle or A2AR agonist (ATL1223 or Regadenoson) infusion during extracorporeal membrane oxygenation. Animals were weaned off extracorporeal membrane oxygenation and monitored for 24 h. Clinical and biochemical end points were compared. The administration of A2AR agonists increased survival (P = 0.01) after cardiac arrest compared to vehicle. Markers of neurologic damage including S100 calcium binding protein B and glial fibrillary acidic protein were significantly lower with A2AR agonist treatment. In a model of cardiac arrest treated with ECPR, A2AR agonism increased survival at 24 h and reduced neurologic damage suggesting A2AR activation may be a promising therapeutic target after cardiac arrest. [ABSTRACT FROM AUTHOR]

Acute hyperglycemia (HG) enhances inflammatory and oxidative stress and exacerbates myocardial infarct size during ischemia-reperfusion injury by activating splenic leukocytes. Formyl peptide receptor 1 (FPR1) on leukocytes is activated by and mediates myocardial ischemia-reperfusion injury. We hypothesize that selective FPR1 antagonist cinnamoyl-F-(D)L-F-(D)L-F (CF) or potent reducing agent tris (2-carboxyethyl) phosphine hydrochloride (TCEP) could abrogate hyperglycemic infarct exacerbation, both alone and synergistically via a novel CF-TCEP compound that would target leukocytes for antioxidative effect. Acute HG was induced in wild type mice with an intraperitoneal dextrose injection followed by left coronary artery occlusion (30 min) and reperfusion (60 min). In treatment groups, CF (0.1 mg/kg or 1 mg/kg), TCEP (1 mg/kg or 20 mg/kg), or the CF-TCEP conjugate (0.1 mg/kg) was administered intravenously before reperfusion. The hearts were harvested to measure infarct size (IF). HG resulted in >50% increase in IF compared to euglycemic mice (52.1 ± 3.0 versus 34.0 ± 3.2%, P < 0.05). Neither CF nor TCEP independently exerted an infarct-sparing effect at lower doses (46.2 ± 2.1% or 50.9 ± 4.1%, P > 0.05 versus HG control) but at high doses, significantly attenuated IF exacerbation (23.2 ± 5.2% or 33.9 ± 3.6%, P < 0.05 versus HG control). However, the low-dose CF-TCEP conjugate significantly reduced IF (39.1 ± 1.7%, P < 0.05 versus HG control). IF was decreased to near euglycemic control levels (P > 0.05). The CF-TECP conjugate synergistically attenuated HG infarct exacerbation at significantly lower respective doses of CF and TCEP. In addition to the intrinsic anti-inflammatory effect of blocking FPR1, CF is also a feasible tool for leukocyte-targeted therapy to treat IRI. [ABSTRACT FROM AUTHOR]

Background: Machine perfusion (MP) offers extended preservation of vascularized complex allografts (VCA), but the diagnostic value of histology using hematoxylin and eosin (H&E) in detecting ischemia–reperfusion injury (IRI) in muscle cells remains unclear. This study aims to document the application of the Histology Injury Severity Score (HISS) and to assess whether additional staining for nicotinamide adenine dinucleotide (NADH) and membrane attack complex (MAC) improves IRI detection in a porcine limb replantation model. Methods: The forelimbs of 16 Dutch Landrace pigs were amputated and preserved for 24 h using hypothermic MP (n = 8) with Histidine-Tryptophan-Ketoglutarate (HTK) or for 4 h with SCS (n = 8) before heterotopic replantation and 7 days of follow-up. Muscle damage was assessed via biochemical markers and light microscopy using H&E, NADH, and MAC at baseline, post-intervention, and post-operative day (POD) 1, 3, and 7 timepoints, using the HISS and a self-developed NADH and MAC score. Results: H&E effectively identified damaged muscle fibers and contributed to IRI assessment in porcine limbs (p < 0.05). The highest HISS was measured on POD 3 between MP (4.9) and SCS (3.5) (p = 0.029). NADH scores of both preservation groups varied over the 7-day follow-up and were statistically insignificant compared with baseline measurements (p > 0.05). MAC revealed no to minimal necrotic tissue across the different timepoints. Conclusions: This study documents the application of the HISS with H&E to detect IRI in muscle fibers. NADH and MAC showed no significant added diagnostic utility. The 24 h MP showed similar muscle alterations using the HISS compared to that of the 4 h SCS after a 7-day follow up. [ABSTRACT FROM AUTHOR]

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 multidrug 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 six-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 three unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT, 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 the 30-min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP. NEW & NOTEWORTHY: We developed a computational model of sodium fluorescein (SF) biliary excretion in ex vivo machine perfusion and used this model to assess changes in model parameters associated with the activity of MRP2, a hepatocyte membrane transporter, in response to increasing warm ischemia time. We found a significant decrease in the parameter value describing MRP2 activity, consistent with a role of decreased MRP2 function in ischemia-reperfusion injury leading to decreased secretion of SF into bile. [ABSTRACT FROM AUTHOR]

Limb dismemberment injuries are common in clinical practice, and safe and effective protection of the dismembered limb is the key to successful limb replantation. Normothermic machine perfusion has made significant breakthrough in the field of organ transplantation, which may maintain the active function of organs and tissues for a long period of time and prolong the preservation time. These findings have been validated in large animal models and clinical trials. Meantime, this technology is expected to provide novel reference for the preservation and functional recovery of severed limbs. Therefore, this paper reviews the problems of static cold preservation in the preservation of disarticulated limbs, the development history of mechanical perfusion, the current status of clinical application of ambient mechanical perfusion of disarticulated limbs as well as the problems to be solved, and looks forward to the direction of its development and the prospect of its clinical application, with a view to promoting the wide application of this technology in the clinic. [ABSTRACT FROM AUTHOR]

Objective To evaluate the protective effect and underlying mechanism of ulinastatin on hepatic ischemia-reperfusion injury. Methods Twenty-four male SD rats were divided into three groups: sham operation group (Sham group), hepatic ischemia-reperfusion injury group (HIRI group) and hepatic ischemia-reperfusion injury + ulinastatin pretreatment group (HIRI+UTI group), with 8 rats in each group. The HIRI rat models were established by occluding hepatic portal vein and hepatic artery for 1 h. In the HIRI+UTI group, the rats were intraperitoneally injected with ulinastatin at 30 min before model establishment, and an equivalent amount of normal saline was given in the Sham and HIRI groups. The rats were sacrificed at 6 h after model establishment. Serum samples were collected to detect alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. Ultrastructural changes of mitochondria in liver tissues were observed by transmission electron microscopy. The expression of glutathione peroxidase 4 (GPX4) was determined by immunofluorescent staining. The contents of malondialdehyde (MDA), glutathione (GSH), Fe, reactive oxygen species (ROS) and GPX4 were detected. The expression levels of GPX4 and acyl-CoA synthetase long-chain family 4 (ACSL4) messenger RNA (mRNA) and proteins in liver tissue were measured. Results Compared with the Sham group, serum ALT and AST levels were up-regulated, pathological changes such as congestion, hepatocyte necrosis and abnormal hepatic lobule structure were observed, pathological score was increased, the mitochondria shrank, the membrane density was increased, the mitochondrial crest was damaged or even absent, the contents of ROS, MDA and Fe were elevated, the GSH content was decreased, the fluorescent intensity of GPX4 was weakened, the relative expression levels of ACSL4 mRNA and protein were up-regulated, and the relative expression levels of GPX4 mRNA and protein were down-regulated in the HIRI group (all P<0.05). Compared with the HIRI group, serum ALT and AST levels were down-regulated, liver tissue injury was alleviated, pathological score was decreased, mitochondrial shrinkage and crest breakage were mitigated, the contents of ROS, MDA and Fe were down-regulated, the GSH content was up-regulated, the fluorescent intensity of GPX4 was enhanced, the relative expression levels of ACSL4 mRNA and protein were down-regulated, and the relative expression levels of GPX4 mRNA and protein were up-regulated in the HIRI+UTI group (all P<0.05). Conclusions Ulinastatin may alleviate hepatic ischemia-reperfusion injury in rats probably through inhibiting ferroptosis. [ABSTRACT FROM AUTHOR]

Objective To evaluate the preservation effect of normothermic mechanical perfusion with red blood cells from humanized genetically modified pig on severed human limbs. Methods Severed human limbs were perfused with red blood cells from humanized genetically modified pigs for 6 h. Perfusion solution was taken every hour to measure the oxygen partial pressure, Na+, K+, Ca2+, pH value, glucose, lactic acid and creatine kinase levels. Superficial flexor muscle was sampled to detect the changes of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-1 levels. At 0 and 6 h after perfusion, the superficial flexor muscles of the forearm were taken for pathological examination. Intercellular space and glycogen consumption of skeletal muscles were observed. An appropriate amount of forearm vessels was collected every 2 h to detect the apoptosis of vascular endothelial cells. X-ray angiography was performed before perfusion and 6 h after perfusion to observe the filling degree of finger-tip peripheral vessels. Results The oxygen partial pressure was observed in the normal range throughout the perfusion. Na+ concentration peaked at 1 h, reaching 138.7 mmol/L, and then fluctuated within the normal range. K+ level peaked at 2 h up to 6.08 mmol/L, then decreased and fluctuated within the normal range. Ca2+ concentration reached the peak at 4 h, up to 1.03 mmol/L. Glucose level was gradually decreased at the beginning of perfusion, reaching the lowest value of 17.7 mmol/L at 2h after perfusion, and then maintained a dynamic balance. The pH value was decreased to 7.28 at 6 h after perfusion. The lactic acid level was increased to 9.6 mmol/L at 1 h after perfusion, and then gradually decreased. The creatine kinase level was increased at the start of perfusion, reached the peak at 2 h up to 20 030 U/L, then decreased and remained stable at the end of perfusion. At the end of perfusion, the morphology of muscle fibers was normal, the gap among muscle fibers was expanded slightly, and the glycogen of skeletal muscles was not significantly accumulated. At 0 h perfusion, the number of apoptotic cells in vascular endothelial cells was large, which was declined at 6 h perfusion. Evident vascular filling was observed at 0 h, and the filling degree of some finger-tip vessels was decreased at 6 h. Conclusions Normothermic mechanical perfusion of severed human limbs with red blood cells from humanized genetically modified pigs may continuously and stably supply energy and oxygen, adjust the ion pH balance of perfusion solution, maintain normal cellular metabolism and exerts certain protective effect upon severed human limbs. [ABSTRACT FROM AUTHOR]

Introduction: The occurrence of lung ischemia-reperfusion injury (LIRI) after lung transplantation results in primary graft dysfunction (PGD) in more than 50% of cases, which seriously affects the prognosis of recipients. Currently, donor lung protection is the focus of research on improving graft survival in lung transplant recipients. Dexmedetomidine (Dex) is a widely used general anesthesia adjuvant in clinical practice to alleviate ischemia-reperfusion injury in the lungs, liver, heart, kidneys, and brain. However, intravenous infusion of Dex can cause negative effects on the cardiovascular system. Inhaling nebulized Dex can directly act on the alveolar tissue and alleviate its cardiovascular inhibitory effect by reducing drug intake. This study aimed to investigate the effect of donor nebulized Dex inhalation on LIRI after lung transplantation in rats. Methods: We randomly divided the male Sprague-Dawley rats into donor rats and recipient rats, and allowed the donor rats to inhale nebulized Dex or physiological saline 15 min before surgery. The donor lung was refrigerated for 8 h before each single-lung transplant. After 2 h of reperfusion of the transplanted lung, serum and transplanted lung tissue were collected. The wet-to-dry weight ratio of the lung tissue was measured, arterial blood gas was detected, and histopathology changes, oxidative stress, inflammatory reactions, and apoptosis were evaluated. Results: Pretransplant inhalation of Dex through the donor's lung reduced the injury of the transplanted lung, increased the levels of malondialdehyde and myeloperoxidase, and decreased the levels of superoxide dismutase and glutathione in the lung tissue. Moreover, nebulized Dex inhalation of the donor lung inhibited LIRI-induced tumor necrosis factor-α, interleukin-6, and inducible nitric oxide synthase expression and also suppressed nuclear factor kappa B phosphorylation. Nebulized Dex inhalation reduced the rate of cell apoptosis in the transplanted lung tissue by inhibiting the upregulation of Bax, downregulation of Bcl-2, and increase in caspase-3 lysis caused by LIRI. Conclusion: Inhalation of atomized Dex is a potential donor lung protection strategy, which can be used to reduce LIRI after lung transplantation and may be helpful to improve the occurrence of PGD and prognosis of lung transplant recipients. [ABSTRACT FROM AUTHOR]

Prompt reperfusion after cerebral ischemia is important to maintain neuronal survival and reduce permanent disability and death. However, the resupply of blood can induce oxidative stress, inflammatory response and apoptosis, further leading to tissue damage. Here, we report the versatile biological roles of transcript-induced in spermiogenesis 40 (Tisp40) in ischemic stroke. We found that the expression of Tisp40 was upregulated in ischemia/reperfusion-induced brain tissues and oxygen glucose deprivation/returned -stimulated neurons. Tisp40 deficiency increased the infarct size and neurological deficit score, and promoted inflammation and apoptosis. Tisp40 overexpression played the opposite role. In vitro, the oxygen glucose deprivation/returned model was established in Tisp40 knockdown and overexpression primary cultured cortical neurons. Tisp40 knockdown can aggravate the process of inflammation and apoptosis, and Tisp40 overexpression ameliorated the aforementioned processes. Mechanistically, Tisp40 protected against ischemic stroke via activating the AKT signaling pathway. Tisp40 may be a new therapeutic target in brain ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (IR) injury contributes to primary graft dysfunction, a major cause of early mortality after lung transplantation. Transcriptomics uses high-throughput techniques to profile the RNA transcripts within a sample and provides a unique view of the mechanisms underlying various biological processes. This review aims to highlight the applications of transcriptomics in lung IR injury studies, which have thus far revealed inflammatory responses to be the major event activated by IR, identified potential biomarkers and therapeutic targets, and investigated the mechanisms of therapeutic interventions. Ex vivo lung perfusion, together with advanced bioinformatic and transcriptomic techniques, including single-cell RNA-sequencing, microRNA profiling, and multi-omics, continue to expand the capabilities of transcriptomics. In the future, the construction of biospecimen banks and the promotion of international collaborations among clinicians and researchers have the potential to advance our understanding of IR injury and improve the management of lung transplant recipients. [ABSTRACT FROM AUTHOR]

Oxidative phosphorylation is regulated by mitochondrial calcium (Ca2+) in health and disease. In physiological states, Ca2+ enters via the mitochondrial Ca2+ uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca2+ homeostasis is critical: insufficient Ca2+ impairs stress adaptation, and Ca2+ overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca2+ dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia. Several themes emerge from recent data. First, mitochondrial Ca2+ regulation is critical for fuel substrate selection, metabolite import, and matching of ATP supply to demand. Second, mitochondrial Ca2+ regulates both the production and response to reactive oxygen species (ROS), and the balance between its pro- and antioxidant effects is key to how it contributes to physiological and pathological states. Third, Ca2+ exerts localized effects on the electron transport chain (ETC), not through traditional allosteric mechanisms but rather indirectly. These effects hinge on specific transporters, such as the uniporter or the Na+/Ca2+ exchanger, and may not be noticeable acutely, contributing differently to phenotypes depending on whether Ca2+ transporters are acutely or chronically modified. Perturbations in these novel relationships during disease states may either serve as compensatory mechanisms or exacerbate impairments in oxidative phosphorylation. Consequently, targeting mitochondrial Ca2+ holds promise as a therapeutic strategy for a variety of cardiac diseases characterized by contractile failure or arrhythmias. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ischemia-reperfusion injury (IRI) is a phenomenon that affects transplant survival. The aim of our study was to examine the effects of IRI in isogenic and allogeneic muscle and skin transplantation models exposed to prolonged warm ischemia. METHODS: Forty-eight Lewis rats and 16 Brown-Norway rats were used to create four groups: Isogenic Inguinal Flap Transplantation (IST), Isogenic Gastrocnemius Muscle Flap Transplantation (IMT), Allogeneic Inguinal Flap Transplantation (AST), and Allogeneic Gastrocnemius Muscle Flap Transplantation (AMT). Malonyldialdehyde (MDA) and superoxide dismutase (SOD) levels were measured on postoperative days 1, 7, 21, 35, 63, 100, and 120 in all groups. Donor-specific chimerism (DSC) in peripheral blood was evaluated in the allogeneic groups on postoperative days 7, 21, 35, 63, 100, and 120. The microRNA-21 and microRNA-205 levels were evaluated on postoperative days 1, 7, and 120 in all groups. At the end of the study, a histopathological examination was performed. RESULTS: A statistically significant difference was found between the groups in terms of MDA and SOD levels. DSC was detected in the AMT group. A significant increase in microRNA-205 was observed, especially in the AMT group. There was no significant difference in the number of functional muscle units between the muscle transplantation groups. CONCLUSION: The presence of DSC in the AMT group and the lack of a significant difference in the number of functional muscle units in the IMT and AMT groups are noteworthy findings. [ABSTRACT FROM AUTHOR]

Hepatic ischemia–reperfusion injury (IRI) is a major cause of postoperative hepatic dysfunction and liver failure involving cellular damage to previously ischemic tissues to which blood flow is restored. The reestablishment of blood flow is essential for salvaging ischemic tissues. The reperfusion itself, however, can paradoxically lead to further cellular damage, which involves a multi-factorial process resulting in extensive tissue damage, which can threaten the function and viability of the liver and other organ systems. The following review outlines multiple models for in-lab analysis of the various hepatic IRI mechanisms, including murine, porcine, cell lines, and machine perfusion models. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury (IRI) during orthotopic liver transplantation (OLT) contributes to graft rejection and poor clinical outcomes. The disulfide form of high mobility group box 1 (diS-HMGB1), an intracellular protein released during OLT-IRI, induces pro-inflammatory macrophages. How diS-HMGB1 differentiates human monocytes into macrophages capable of activating adaptive immunity remains unknown. We investigated if diS-HMGB1 binds toll-like receptor (TLR) 4 and TLR9 to differentiate monocytes into pro-inflammatory macrophages that activate adaptive immunity and promote graft injury and dysfunction. Assessment of 106 clinical liver tissue and longitudinal blood samples revealed that OLT recipients were more likely to experience IRI and graft dysfunction with increased diS-HMGB1 released during reperfusion. Increased diS-HMGB1 concentration also correlated with TLR4/TLR9 activation, polarization of monocytes into pro-inflammatory macrophages, and production of anti-donor antibodies. In vitro, healthy volunteer monocytes stimulated with purified diS-HMGB1 had increased inflammatory cytokine secretion, antigen presentation machinery, and reactive oxygen species production. TLR4 inhibition primarily impeded cytokine/chemokine and costimulatory molecule programs, whereas TLR9 inhibition decreased HLA-DR and reactive oxygen species production. diS-HMGB1-polarized macrophages also showed increased capacity to present antigens and activate T memory cells. In murine OLT, diS-HMGB1 treatment potentiated ischemia-reperfusion-mediated hepatocellular injury, accompanied by increased serum alanine transaminase levels. This translational study identifies the diS-HMGB1/TLR4/TLR9 axis as potential therapeutic targets in OLT-IRI recipients.

Abstract Background Numerous studies have explored the effects of L-arginine, whether administered in the form of a supplement or through infusion during cardioplegia, on cardiac and inflammatory markers in individuals undergoing coronary artery bypass grafting (CABG). However, these studies presented contradictory findings. Consequently, the objective of this study was to investigate the impact of l-arginine on these markers by analyzing available randomized controlled trials (RCTs). Methods We performed an extensive search across various databases, including Embase, Medline/PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar, covering research published until December 2023. To analyze the mean changes in inflammatory and cardiac markers between the L-arginine and control groups, we calculated the weighted mean difference (WMD) along with the corresponding 95% confidence interval (CI) using a random-effects model. Results A total of 393 RCTs were identified during the initial search. After screening and selection, 7 trials were included. In a meta-analysis of three trials that reported troponin T levels, we found a significant impact of L-arginine on reducing troponin T levels (WMD = -0.61 ng/ml; 95% CI: -1.07, -0.15). Our analysis also showed that L-arginine had a noticeable impact on decreasing interleukin-6 (IL-6) levels (WMD = -7.72 pg/ml; 95% CI: -15.05, -0.39). However, we found no considerable impact of L-arginine treatment on creatine phosphokinase-MB (CPK-MB), tumor necrosis factor-alpha (TNF-α), and troponin I compared to the placebo groups. Conclusions Our findings suggest that L-arginine may benefit patients undergoing CABG, as it helps reduce inflammatory reactions and limits myocardial ischemia. This study registered in the PROSPERO database (Registration No. CRD42024508341).

Ischemia–reperfusion injury (IRI) is a predominant factor leading to delayed graft function (DGF) following kidney transplantation. MicroRNAs (miRNAs) play a pivotal role in the pathogenesis of renal IRI, with ferroptosis being a critical driving force throughout the process. In this study, we utilized bioinformatics methods to construct a network diagram of differentially expressed miRNAs, transcription factors (TFs), and ferroptosis-related genes. An I/R-induced renal injury model in mice and an in vitro H/R-induced HK-2 cell injury model were established. Quantitative real-time PCR (qRT-PCR) and Western blot analysis were used to measure the mRNA and miRNA levels in cells and tissues. The MDA concentration, iron levels, and GSH concentration were measured to evaluate the ferroptosis levels. CCK-8 assays were performed to assess cell viability. Luciferase reporter assays were conducted to validate the downstream targets of miRNA, and chromatin immunoprecipitation assays were performed to verify the interaction between TFs and mRNAs. Both the in vivo and in vitro results demonstrate that miR-451a was significantly enriched in the IRI renal tissues and cells, exacerbating ferroptosis. MiR-451a was found to reduce the expression of Kruppel-like factor 1 (KLF1) by directly binding to the 3′UTR of KLF1 mRNA. Additionally, KLF1 was identified as a negative transcription factor for acyl-CoA synthetase long-chain family member 4 (ACSL4). We demonstrated that IRI induced the upregulation of miR-451a, which reduced KLF1 expression, thereby promoting ferroptosis by upregulating ACSL4 expression, ultimately aggravating IRI-induced renal damage.

Abstract Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg-1) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-α (p = 0.02), IL-6 (p = 0.001), IL-1β (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx.

Accumulation of reactive oxygen species during testicular torsion causes oxidative stress, which in turn causes ischemia-reperfusion (I/R) injury to the testis. In testicular torsion/detorsion (T/D) in male mice, the purpose of this study was to investigate the influence of Mito-TEMPO (MT) on I/R injury. Forty-two male mice were divided into seven groups, including a control group and six treatment groups (360° T/D, 720° T/D, 360° T/D + 0.70 mg/kg MT, 360° T/D + 1 mg/kg MT, 720° T/D + 0.70 mg/kg MT and 720° T/D + 1 mg/kg MT). After inducing testicular torsion, oxidative enzymes, and testicular histopathology were evaluated. The results showed that 720° T/D resulted in increased testicular malondialdehyde levels and histological damage, along with reduced activities of catalase, superoxide dismutase, and glutathione peroxidase. Treatment with MT reduced tissue malondialdehyde levels and increased the activities of catalase, superoxide dismutase, and glutathione peroxidase. These findings suggest that MT administration protects against acute testicular T/D injury in mice.

Abstract Background At present, hepatic ischemia-reperfusion injury (IRI) is an important complication of partial hepatectomy and liver transplantation, and it is an important cause of poor prognosis. Spleen tyrosine kinase(SYK) plays an important role in a variety of signaling pathways in the liver, but its role in hepatic IRI is still unclear. This study aims to investigate the role and mechanism of SYK in hepatic IRI and tumor recurrence. Methods We first observed the activation of SYK in the liver of mice in response to hepatic IRI. Subsequently, Pharmacological inhibitions of SYK were used to evaluated the effect of SYK on neutrophil recruitment and NETosis, and further explored the effect of SYK on IRI and tumor recurrence. Results Our study shows that SYK is activated in response to hepatic IRI and aggravates liver injury. On the one hand, neutrophils SYK during the early stage of liver reperfusion increases neutrophil extracellular traps (NETs) production by promoting Pyruvate kinase M2(PKM2) nuclear translocation leading to upregulation of phosphorylated STAT3, thereby exacerbating liver inflammation and tumor recurrence. On the other hand, macrophages SYK can promote the recruitment of neutrophils and increase the activation of NLRP3 inflammasome and IL1β, which further promotes the formation of NETs. Conclusions Our study demonstrates that neutrophil and macrophage SYK synergistically promote hepatic IRI and tumor recurrence, and SYK may be a potential target to improve postoperative hepatic IRI and tumor recurrence.

Proprotein convertase substilin/kexin type 9 (PCSK9), a pivotal protein regulating lipid metabolism, has been implicated in promoting microthrombotic formation and inflammatory cascades, thereby contributing to cardiovascular ischemia/reperfusion (I/R) injury. However, its involvement in cerebral I/R injury and its potential role in microcirculation protection remain unexplored. In this investigation, we utilized a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to simulate ischemic stroke. Different concentrations of evolocumab (1, 5, 10 mg/kg, i.v.), a PCSK9 inhibitor, were administered to assess its impact. Immunofluorescence staining was employed to analyze changes in the expression of occludin, claudin-5, thrombocyte, ICAM-1, VCAM-1, and CD45, providing insights into blood-brain barrier integrity, platelet adhesion, and immune cell infiltration. Moreover, the Morris water maze and elevated plus maze were utilized to evaluate neurological and behavioral functions in MCAO/R mice, shedding light on the effects of PCSK9 inhibition. Our findings revealed a surge in plasma PCSK9 levels post-MCAO/R, peaking at 24 h post-reperfusion. Evolocumab (10 mg/kg) treatment significantly mitigated brain infarction and neurological deficits, evidenced by enhanced locomotor function and reduced post-stroke anxiety. However, it did not ameliorate cognitive impairment following MCAO/R. Additionally, evolocumab administration led to diminished leakage of evans blue solution and upregulated expression of occludin and claudin-5. Thrombocyte, ICAM-1, VCAM-1, and CD45 levels were notably reduced in the penumbral area post-evolocumab treatment. These protective effects are speculated to be mediated through the inhibition of the ERK/NF-κB pathway. The PCSK9 inhibitor evolocumab holds promise as a therapeutic agent during the acute phase of stroke, exerting its beneficial effects by modulating the ERK/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

The preclinical efficacy of mesenchymal stem cell (MSC) therapy after intravenous infusion has been promising, but clinical studies have yielded only modest results. Although most preclinical studies have focused solely on the ischemic lung, it is crucial to evaluate both lungs after ischemia-reperfusion injury, considering the various mechanisms involved. This study aimed to bridge this gap by assessing the acute effects of bone marrow MSC(BM) infusion before ischemic insult and evaluating both ischemic and non-ischemic lungs after reperfusion. Eighteen male Wistar rats (403 ± 23 g) were anesthetized and mechanically ventilated using a protective strategy. After baseline data collection, the animals were randomized to 3 groups (n = 6/group): (1) SHAM; (2) ischemia-reperfusion (IR), and (3) intravenous MSC(BM) infusion followed by IR. Ischemia was induced by complete clamping of the left hilum, followed by 1 h of reperfusion after clamp removal. At the end of the experiment, the right and left lungs (non-ischemic and ischemic, respectively) were collected for immunohistochemistry and molecular biology analysis. MSC(BM)s reduced endothelial cell damage and apoptosis markers and improved markers associated with endothelial cell integrity in both lungs. In addition, gene expression of catalase and nuclear factor erythroid 2-related factor 2 increased after MSC(BM) therapy. In the ischemic lung, MSC(BM) therapy mitigated endothelial cell damage and apoptosis and increased gene expression associated with endothelial cell integrity. Conversely, in the non-ischemic lung, apoptosis gene expression increased in the IR group but not after MSC(BM) therapy. This study demonstrates distinct effects of MSC(BM) therapy on ischemic and non-ischemic lungs after ischemia-reperfusion injury. The findings underscore the importance of evaluating both lung types in ischemia-reperfusion studies, offering insights into the therapeutic potential of MSC(BM) therapy in the context of lung injury. [Display omitted] • MSC therapy in the contralateral lung with IRI is an emerging area of research. • Markers of endothelial cell integrity increased after MSC(BM) therapy. • Levels of antioxidative enzyme increased after MSC(BM) therapy. • MSC(BM) therapy prevented lung IRI in ischemic and non-ischemic lungs. [ABSTRACT FROM AUTHOR]

Yu-Qing Tan,1,&ast; Wang Zhang,2,&ast; Zi-Cong Xie,1 Jun Li,1 Heng-Wen Chen3 1Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 2Department of Pharmacy, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 3New Drug Research and Development Office, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li; Heng-Wen Chen, Email 13051458913@163.com; chenhengwen@163.comAbstract: Cardiovascular diseases (CVDs) tend to affect the young population and are associated with a significant economic burden and psychological distress to the society and families. The physiological and pathological processes underlying CVDs are complex. Ca2+/calmodulin-dependent kinase II (CaMK II), a protein kinase, has multiple biological functions. It participates in multiple pathological processes and plays a central role in the development of CVDs. Based on this, this paper analyzes the structural characteristics and distribution of CaMK II, the mechanism of action of CaMK II, and the relationship between CaMK II and CVDs, including ion channels, ischemia-reperfusion injury, arrhythmias, myocardial hypertrophy, cardiotoxicity, hypertension, and dilated cardiomyopathy. Given the different regulatory mechanisms of different isoforms of CaMK II, the clinical use of specific targeted inhibitors or novel compounds should be evaluated in future research to provide new directions.Keywords: CaMK II, cardiovascular diseases, ischemia-reperfusion injury, arrhythmias, myocardial hypertrophy

The shortage of organs for transplant remains a major challenge in transplantology. Transporting donor organs over long distances increases cold ischemia time, which is a risk factor for ischemia-reperfusion injury (IRI). In the face of critical shortages, the method and timing of organ preservation are crucial in increasing the donor pool. This paper examines the approaches, benefits, and drawbacks of organ preservation techniques used around the world.