scholarly journals Sequence of reperfusion influences ischemia/reperfusion injury and primary graft function following porcine liver transplantation

2005 ◽  
Vol 11 (10) ◽  
pp. 1214-1222 ◽  
Author(s):  
Jens G. Brockmann ◽  
Christian August ◽  
Heiner H. Wolters ◽  
Ralf Hömme ◽  
Daniel Palmes ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Porcine Liver ◽  
Porcine Liver Transplantation

scholarly journals EPOR2/βcR2-independendent effects of low-dose epoetin-α in porcine liver transplantation

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Linus Kebschull ◽  
Leon Franz Christoph Theilmann ◽  
Annika Mohr ◽  
Wencke Uennigmann ◽  
Sandra Stoeppeler ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Low Dose ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Porcine Liver ◽  
Ischemic Time ◽  
Apoptotic Effects ◽  
Endothelial Nitric Oxide ◽  
Porcine Liver Transplantation

Ischemia–reperfusion injury (IRI) remains a key component of graft damage during transplantation. Erythropoietin (EPO) induces anti-inflammatory and anti-apoptotic effects via the EPOR2/βcR2 complex, with a potential risk of thrombosis. Previous work indicates that EPO has EPOR2/βcR2-independent protective effects via direct effects on the endothelium. As the EPOR2/βcR2 receptor has a very low affinity for EPO, we aimed to test the hypothesis that EPO doses below the level that stimulate this receptor elicit cytoprotective effects via endothelial stimulation in a porcine liver transplantation model. Landrace pigs underwent allogenic liver transplantation (follow-up: 6 h) with a portojugular shunt. Animals were divided into two groups: donor and recipient treatment with low-dose EPO (65 IU/kg) or vehicle, administered 6 h before cold perfusion and 30 min after warm reperfusion. Fourteen of 17 animals (82.4%) fulfilled the inclusion criteria. No differences were noted in operative values between the groups including hemoglobin, cold or warm ischemic time. EPO-treated animals showed a significantly lower histopathology score, reduced apoptosis, oxidative stress, and most important a significant up-regulation of endothelial nitric oxide (NO) synthase (eNOS). Donor and recipient treatment with low-dose EPO reduces the hepatic IRI via EPOR2/βcR2-independent cytoprotective mechanisms and represents a clinically applicable way to reduce IRI.

scholarly journals Beneficial effects of end-ischemic oxygenated machine perfusion preservation for split-liver transplantation in recovering graft function and reducing ischemia–reperfusion injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daisuke Ishii ◽  
Naoto Matsuno ◽  
Mikako Gochi ◽  
Hiroyoshi Iwata ◽  
Tatsuya Shonaka ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Autologous Blood ◽  
Graft Function ◽  
Machine Perfusion ◽  
Perfusion System ◽  
Split Liver Transplantation ◽  
Split Liver

AbstractThis study examined the efficacy of end-ischemic hypothermic oxygenated machine perfusion preservation (HOPE) using an originally developed machine perfusion system for split-liver transplantation. Porcine split-liver grafts were created via 75% liver resection after 10 min of warm ischemia. In Group 1, grafts were preserved by simple cold storage (CS) for 8 h (CS group; n = 4). In Group 2, grafts were preserved by simple CS for 6 h and end-ischemic HOPE for 2 h (HOPE group; n = 5). All grafts were evaluated using an isolated ex vivo reperfusion model with autologous blood for 2 h. Biochemical markers (aspartate aminotransferase and lactate dehydrogenase levels) were significantly better immediately after reperfusion in the HOPE group than in the CS group. Furthermore, the HOPE group had a better histological score. The levels of inflammatory cytokines (tumor necrosis factor-α, interferon-γ, interleukin-1β, and interleukin-10) were significantly lower after reperfusion in the HOPE group. Therefore, we concluded that end-ischemic HOPE for split-liver transplantation can aid in recovering the graft function and reducing ischemia–reperfusion injury. HOPE, using our originally developed machine perfusion system, is safe and can improve graft function while attenuating liver injury due to preservation.

scholarly journals New Insights in Mechanisms and Therapeutics for Short- and Long-Term Impacts of Hepatic Ischemia Reperfusion Injury Post Liver Transplantation

2021 ◽  
Vol 22 (15) ◽  
pp. 8210
Author(s):  
Hui Liu ◽  
Kwan Man
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Cancer Recurrence ◽  
Short Term ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Liver transplantation has been identified as the most effective treatment for patients with end-stage liver diseases. However, hepatic ischemia reperfusion injury (IRI) is associated with poor graft function and poses a risk of adverse clinical outcomes post transplantation. Cell death, including apoptosis, necrosis, ferroptosis and pyroptosis, is induced during the acute phase of liver IRI. The release of danger-associated molecular patterns (DAPMs) and mitochondrial dysfunction resulting from the disturbance of metabolic homeostasis initiates graft inflammation. The inflammation in the short term exacerbates hepatic damage, leading to graft dysfunction and a higher incidence of acute rejection. The subsequent changes in the graft immune environment due to hepatic IRI may result in chronic rejection, cancer recurrence and fibrogenesis in the long term. In this review, we mainly focus on new mechanisms of inflammation initiated by immune activation related to metabolic alteration in the short term during liver IRI. The latest mechanisms of cancer recurrence and fibrogenesis due to the long-term impact of inflammation in hepatic IRI is also discussed. Furthermore, the development of therapeutic strategies, including ischemia preconditioning, pharmacological inhibitors and machine perfusion, for both attenuating acute inflammatory injury and preventing late-phase disease recurrence, will be summarized in the context of clinical, translational and basic research.

scholarly journals The impact of desflurane and sevoflurane on the intraoperative and early postoperative period in liver transplantation

2021 ◽  
Vol 13 (4) ◽  
pp. 328-338
Author(s):  
S. V. Zhuravel ◽  
N. K. Kuznetsova ◽  
V. E. Aleksandrova ◽  
I. I. Goncharova
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Postoperative Period ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Early Postoperative Period ◽  
Liver Graft ◽  
Inhalation Anesthetics ◽  
The Impact

Background. A pressing issue is the choice of an anesthetic agent for liver transplantation. The mechanism of the organprotective properties of desflurane and sevoflurane is not fully understood. It is important to understand the effects of desflurane and sevoflurane on the severity of ischemia-reperfusion injury of the liver graftAim. To study the effect of desflurane and sevoflurane on the intraoperative and early postoperative period in liver transplantation.Material and methods. The study included 47 patients with liver cirrhosis of various etiologies who underwent cadaveric liver transplantation between February and December 2020. The groups compared in the study included 24 patients who received desflurane and 23 patients who received sevoflurane.Results. There were no statistically significant differences in the effect of desflurane and sevoflurane on hemodynamic parameters, on the need for vasopressor drugs. Episodes of bradycardia and cardiac arrhythmias were significantly more frequent when using sevoflurane. Patients were extubated significantly faster after surgery in the desflurane group. In the early postoperative period, desflurane and sevoflurane did not adversely affect significantly the liver graft function and the degree of its ischemia-reperfusion injury. The groups appeared comparable in rates of using the renal replacement therapy, the incidence of the graft dysfunction development in the postoperative period, and the surgery outcomes.Conclusions. The use of modern inhalation anesthetics desflurane and sevoflurane to maintain anesthesia during liver transplantation does not adversely affect the course of the intraoperative and early postoperative period.

scholarly journals Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Linhe Wang ◽  
Jie Li ◽  
Shuai He ◽  
Yang Liu ◽  
Haitian Chen ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Single Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Mononuclear Phagocyte ◽  
Interacting Protein ◽  
Cell Clusters ◽  
Cell Transcriptome

AbstractIschemia–reperfusion injury (IRI) remains the major reason for impaired donor graft function and increased mortality post-liver transplantation. The mechanism of IRI involves multiple pathophysiological processes and numerous types of cells. However, a systematic and comprehensive single-cell transcriptional profile of intrahepatic cells during liver transplantation is still unclear. We performed a single-cell transcriptome analysis of 14,313 cells from liver tissues collected from pre-procurement, at the end of preservation and 2 h post-reperfusion. We made detailed annotations of mononuclear phagocyte, endothelial cell, NK/T, B and plasma cell clusters, and we described the dynamic changes of the transcriptome of these clusters during IRI and the interaction between mononuclear phagocyte clusters and other cell clusters. In addition, we found that TNFAIP3 interacting protein 3 (TNIP3), specifically and highly expressed in Kupffer cell clusters post-reperfusion, may have a protective effect on IRI. In summary, our study provides the first dynamic transcriptome map of intrahepatic cell clusters during liver transplantation at single-cell resolution.

scholarly journals Impact of Three Methods of Ischemic Preconditioning on Ischemia-Reperfusion Injury in a Pig Model of Liver Transplantation

2021 ◽  
pp. 1-10
Author(s):  
Alessandro Rodrigo Belon ◽  
Ana Cristina Aoun Tannuri ◽  
Daniel de Albuquerque Rangel Moreira ◽  
Jose Luiz Figueiredo ◽  
Alessandra Matheus da Silva ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pig Model

Attenuation of lung reperfusion injury after transplantation using an inhibitor of nuclear factor-κB

2000 ◽  
Vol 279 (3) ◽  
pp. L528-L536 ◽  
Author(s):  
Scott D. Ross ◽  
Irving L. Kron ◽  
James J. Gangemi ◽  
Kimberly S. Shockey ◽  
Mark Stoler ◽  
...  
Keyword(s):  
Lung Function ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Nuclear Factor Κb ◽  
Pyrrolidine Dithiocarbamate ◽  
Nuclear Factor ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

A central role for nuclear factor-κB (NF-κB) in the induction of lung inflammatory injury is emerging. We hypothesized that NF-κB is a critical early regulator of the inflammatory response in lung ischemia-reperfusion injury, and inhibition of NF-κB activation reduces this injury and improves pulmonary graft function. With use of a porcine transplantation model, left lungs were harvested and stored in cold Euro-Collins preservation solution for 6 h before transplantation. Activation of NF-κB occurred 30 min and 1 h after transplant and declined to near baseline levels after 4 h. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-κB, given to the lung graft during organ preservation (40 mmol/l) effectively inhibited NF-κB activation and significantly improved lung function. Compared with control lungs 4 h after transplant, PDTC-treated lungs displayed significantly higher oxygenation, lower Pco2, reduced mean pulmonary arterial pressure, and reduced edema and cellular infiltration. These results demonstrate that NF-κB is rapidly activated and is associated with poor pulmonary graft function in transplant reperfusion injury, and targeting of NF-κB may be a promising therapy to reduce this injury and improve lung function.

scholarly journals Early cytokine signatures of ischemia/reperfusion injury in human orthotopic liver transplantation

JCI Insight ◽  
2016 ◽  
Vol 1 (20) ◽  
Author(s):  
Rebecca A. Sosa ◽  
Ali Zarrinpar ◽  
Maura Rossetti ◽  
Charles R. Lassman ◽  
Bita V. Naini ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Orthotopic Liver Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

scholarly journals Thymoglobulin and ischemia reperfusion injury in kidney and liver transplantation

2007 ◽  
Vol 22 (Supplement 8) ◽  
pp. viii54-viii60 ◽  
Author(s):  
A. Mehrabi ◽  
Zh. A. Mood ◽  
M. Sadeghi ◽  
B. M. Schmied ◽  
S. A. Muller ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion
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