ADP and P2Y13 receptor are involved in the autophagic protection of ex vivo perfused livers from fasted rats: Potential benefit for liver graft preservation

2020 ◽  
Author(s):  
Bérengère Papegay ◽  
Vincent Nuyens ◽  
Adelin Albert ◽  
Mustapha Cherkaoui‐Malki ◽  
Pierre Andreoletti ◽  
...  
Keyword(s):  
Potential Benefit ◽  
Ex Vivo ◽  
Liver Graft ◽  
Graft Preservation ◽  
Fasted Rats

scholarly journals Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach

2021 ◽  
Vol 22 (10) ◽  
pp. 5332
Author(s):  
Raquel G. Bardallo ◽  
Rui Teixeira da Silva ◽  
Teresa Carbonell ◽  
Emma Folch-Puy ◽  
Carlos Palmeira ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fatty Liver ◽  
Liver Graft ◽  
Suitable Alternative ◽  
Graft Preservation ◽  
Preservation Solutions ◽  
Microcirculatory Disturbances ◽  
Organ Recovery ◽  
Surgical Manipulations

The total damage inflicted on the liver before transplantation is associated with several surgical manipulations, such as organ recovery, washout of the graft, cold conservation in organ preservation solutions (UW, Celsior, HTK, IGL-1), and rinsing of the organ before implantation. Polyethylene glycol 35 (PEG35) is the oncotic agent present in the IGL-1 solution, which is an alternative to UW and Celsior solutions in liver clinical transplantation. In a model of cold preservation in rats (4 °C; 24 h), we evaluated the effects induced by PEG35 on detoxifying enzymes and nitric oxide, comparing IGL-1 to IGL-0 (which is the same as IGL-1 without PEG). The benefits were also assessed in a new IGL-2 solution characterized by increased concentrations of PEG35 (from 1 g/L to 5 g/L) and glutathione (from 3 mmol/L to 9 mmol/L) compared to IGL-1. We demonstrated that PEG35 promoted the mitochondrial enzyme ALDH2, and in combination with glutathione, prevented the formation of toxic aldehyde adducts (measured as 4-hydroxynonenal) and oxidized proteins (AOPP). In addition, PEG35 promoted the vasodilator factor nitric oxide, which may improve the microcirculatory disturbances in steatotic grafts during preservation and revascularization. All of these results lead to a reduction in damage inflicted on the fatty liver graft during the cold storage preservation. In this communication, we report on the benefits of IGL-2 in hypothermic static preservation, which has already been proved to confer benefits in hypothermic oxygenated dynamic preservation. Hence, the data reported here reinforce the fact that IGL-2 is a suitable alternative to be used as a unique solution/perfusate when hypothermic static and preservation strategies are used, either separately or combined, easing the logistics and avoiding the mixture of different solutions/perfusates, especially when fatty liver grafts are used. Further research regarding new therapeutic and pharmacological insights is needed to explore the underlying mitochondrial mechanisms exerted by PEG35 in static and dynamic graft preservation strategies for clinical liver transplantation purposes.

The Authors’ Reply: Dynamic liver graft preservation in cDCD: What is the best fit?

2021 ◽  
Author(s):  
Patricia Ruiz ◽  
Andres Valdivieso ◽  
Ibone Palomares ◽  
Mikel Prieto ◽  
Alberto Ventoso ◽  
...  
Keyword(s):  
Liver Graft ◽  
Graft Preservation ◽  
Best Fit

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats

2017 ◽  
Vol 23 (9) ◽  
pp. 1171-1185 ◽  
Author(s):  
Shinya Okumura ◽  
Tadahiro Uemura ◽  
Xiangdong Zhao ◽  
Yuki Masano ◽  
Tatsuaki Tsuruyama ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Cardiac Death ◽  
Liver Graft ◽  
Donation After Cardiac Death ◽  
Graft Preservation

Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles

2015 ◽  
Vol 308 (3) ◽  
pp. E231-E240 ◽  
Author(s):  
Anders J. Kolnes ◽  
Jesper B. Birk ◽  
Einar Eilertsen ◽  
Jorid T. Stuenæs ◽  
Jørgen F. P. Wojtaszewski ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Ex Vivo ◽  
Normal Diet ◽  
Epinephrine Injection ◽  
First Time ◽  
Fasted Rats ◽  
Glycogen Breakdown ◽  
Direct Regulation

Epinephrine increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown, and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated in condition with decreased GS activation. Saline or epinephrine (0.02 mg/100 g rat) was injected subcutaneously in Wistar rats (∼130 g) with low (24-h-fasted), normal (normal diet), and high glycogen content (fasted-refed), and epitrochlearis muscles were removed after 3 h and incubated ex vivo, eliminating epinephrine action. Epinephrine injection reduced glycogen content in epitrochlearis muscles with high (120.7 ± 17.8 vs. 204.6 ± 14.5 mmol/kg, P < 0.01) and normal glycogen (89.5 ± 7.6 vs. 152 ± 8.1 mmol/kg, P < 0.01), but not significantly in muscles with low glycogen (90.0 ± 5.0 vs. 102.8 ± 7.8 mmol/kg, P = 0.17). In saline-injected rats, GS phosphorylation at sites 2+2a, 3a+3b, and 1b was higher and GS activity lower in muscles with high compared with low glycogen. GS sites 2+2a and 3a+3b phosphorylation decreased and GS activity increased in muscles where epinephrine decreased glycogen content; these parameters were unchanged in epitrochlearis from fasted rats where epinephrine injection did not decrease glycogen content. Incubation with insulin decreased GS site 3a+3b phosphorylation independently of glycogen content. Insulin-stimulated glucose uptake was increased in muscles where epinephrine injection decreased glycogen content. In conclusion, epinephrine stimulates glycogenolysis in epitrochlearis muscles with normal and high, but not low, glycogen content. Epinephrine-stimulated glycogenolysis decreased GS phosphorylation and increased GS activity. These data for the first time document direct regulation of GS phosphorylation by glycogen content.

Subnormothermic Ex Vivo Lung Perfusion Improves Graft Preservation in Rat Ex Vivo Lung Perfusion Model

2020 ◽  
Vol 39 (4) ◽  
pp. S354
Author(s):  
N. Citak ◽  
S. Arni ◽  
J. Cehn ◽  
L. Ceulemans ◽  
I. Schmitt-Opitz ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Lung Perfusion ◽  
Ex Vivo Lung Perfusion ◽  
Perfusion Model ◽  
Graft Preservation

The of Institute George Lopez (IGL-1) Solution in Liver Graft Preservation - Experience With 100 Liver Transpant in a Single Center.

2014 ◽  
Vol 98 ◽  
pp. 707
Author(s):  
J. Wiederkehr ◽  
M. Igreja ◽  
M. Nogara ◽  
N. Goncalves ◽  
M. Godoy ◽  
...  
Keyword(s):  
Liver Graft ◽  
Single Center ◽  
Graft Preservation

AMPK involvement in endoplasmic reticulum stress and autophagy modulation after fatty liver graft preservation: a role for melatonin and trimetazidine cocktail

2013 ◽  
Vol 55 (1) ◽  
pp. 65-78 ◽  
Author(s):  
Mohamed Amine Zaouali ◽  
Eleonora Boncompagni ◽  
Russel J. Reiter ◽  
Mohamed Bejaoui ◽  
Isabel Freitas ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Fatty Liver ◽  
Liver Graft ◽  
Graft Preservation

scholarly journals Ex-vivo Liver Splitting during Hypothermic Oxygenated Perfusion: A Novel Procedure to Optimize Graft Preservation in Split Liver Transplantation

HPB ◽  
2021 ◽  
Vol 23 ◽  
pp. S690-S691
Author(s):  
G. Rossignol ◽  
X. Muller ◽  
M. Lesurtel ◽  
R. Dubois ◽  
K. Mohkam ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Ex Vivo ◽  
Split Liver Transplantation ◽  
Graft Preservation ◽  
Split Liver

Cirrhosis as new indication for statins

Gut ◽  
2020 ◽  
Vol 69 (5) ◽  
pp. 953-962 ◽  
Author(s):  
Jaime Bosch ◽  
Jordi Gracia-Sancho ◽  
Juan G Abraldes
Keyword(s):  
Liver Diseases ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Portal Pressure ◽  
Microvascular Dysfunction ◽  
Chronic Liver ◽  
Liver Graft ◽  
Chronic Liver Diseases ◽  
Ischaemia Reperfusion Injury ◽  
Objective Evidence

In the recent years, there have been an increasing number of reports on favourable effects of statins in patients with advanced chronic liver disease. These include reduction in portal pressure, improved liver sinusoidal endothelial and hepatic microvascular dysfunction, decreased fibrogenesis, protection against ischaemia/reperfusion injury, safe prolongation of ex vivo liver graft preservation, reduced sensitivity to endotoxin-mediated liver damage, protection from acute-on-chronic liver failure, prevention of liver injury following hypovolaemic shock and preventing/delaying progression of cirrhosis of any aetiology. Moreover, statins have been shown to have potential beneficial effects in the progression of other liver diseases, such as chronic sclerosing cholangitis and in preventing hepatocellular carcinoma. Because of these many theoretically favourable effects, statins have evolved from being considered a risk to kind of wonder drugs for patients with chronic liver diseases. The present article reviews the current knowledge on the potential applications of statins in chronic liver diseases, from its mechanistic background to objective evidence from clinical studies.

scholarly journals Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation

2020 ◽  
Vol 21 (16) ◽  
pp. 5703 ◽  
Author(s):  
Arnau Panisello Rosello ◽  
Rui Teixeira da Silva ◽  
Carlos Castro ◽  
Raquel G. Bardallo ◽  
Maria Calvo ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Water Soluble ◽  
Liver Graft ◽  
Liver Preservation ◽  
Hypothermic Preservation ◽  
Graft Preservation ◽  
Abdominal Organs ◽  
Good Target

Organ transplantation is a multifactorial process in which proper graft preservation is a mandatory step for the success of the transplantation. Hypothermic preservation of abdominal organs is mostly based on the use of several commercial solutions, including UW, Celsior, HTK and IGL-1. The presence of the oncotic agents HES (in UW) and PEG35 (in IGL-1) characterize both solution compositions, while HTK and Celsior do not contain any type of oncotic agent. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic and water-soluble polymers, which present a combination of properties of particular interest in the clinical context of ischemia-reperfusion injury (IRI): they limit edema and nitric oxide induction and modulate immunogenicity. Besides static cold storage (SCS), there are other strategies to preserve the organ, such as the use of machine perfusion (MP) in dynamic preservation strategies, which increase graft function and survival as compared to the conventional static hypothermic preservation. Here we report some considerations about using PEG35 as a component of perfusates for MP strategies (such as hypothermic oxygenated perfusion, HOPE) and its benefits for liver graft preservation. Improved liver preservation is closely related to mitochondria integrity, making this organelle a good target to increase graft viability, especially in marginal organs (e.g., steatotic livers). The final goal is to increase the pool of suitable organs, and thereby shorten patient waiting lists, a crucial problem in liver transplantation.

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