Hepatic preconditioning after prolonged warm ischemia by means of S-adenosyl-L-methionine administration in pig liver transplantation from non-heart-beating donors

Net, M.; Valero, Ricard; Almenara, R; Deulofeu, R.; López-Boado, M.Á.; Capdevila, Lluís; Barros, Pablo; Bombí, Josep Antoni; Agustí, Mercé; Adàlia, R.; Ruíz, Ángel; Arce, Yolanda; Manyalich, M.; García‐Valdecasas, Juan Carlos

doi:10.1097/01.tp.0000069042.68375.71

Cited by 31 publications

(19 citation statements)

References 30 publications

(32 reference statements)

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“…We have previously demonstrated that survival was closely related to persistence of a good hepatic blood flow (12,35,36). The better the blood flow obtained during NR the better the survival, suggesting that preservation of the vascular bed is a key point in organ viability.…”

Section: Discussionmentioning

confidence: 99%

“…eNOS is expressed in endothelial cells and produces physiological levels of NO, and iNOS, mainly expressed in hepatocytes and kupffer cells, is strongly up-regulated under certain conditions producing large amounts of NO, which increase ischemia-reperfusion damage. Moreover, depending on the cell type and experimental conditions, cAMP may up-regulate eNOS-mediated NO production (36,37) and down-regulate iNOS-mediated NO production at different levels (39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Normothermic Recirculation is Mediated by Ischemic Preconditioning in NHBD Liver Transplantation

Net¹,

Valero²,

Almenara³

et al. 2005

American Journal of Transplantation

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112

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We have evaluated the involvement of hepatic preconditioning mediators (adenosine, adenosine A1 and A2 receptors) during normothermic recirculation (NR) in a model of liver transplantation from non-heart-beating donor (NHBD) pigs.Application of NR after 20 min of warm ischemia (WI) reversed the lethal injury associated with transplantation of NHBD livers (achieving 5-day survival and diminishing glutathione S-transferase (GST), aspartate aminotransferase (AST) and hyaluronic acid (HA)).Adenosine administration prior to WI simulated the effect of NR. Measuring adenosine, we found that during NR, hepatic adenosine levels increased and xanthine levels decreased. Then when we blocked A2 receptors the effect of NR was abolished, whereas the blocking of A1 receptors further protected the liver. Furthermore, A2 blocking improved hepatic perfusion during NR whereas A1 blocking reduced it.The study suggests that NR has a preconditioning effect by maintaining adequate adenosine and xanthine levels. During NR, adenosine protects the liver through A2 activation and damages it through A1 activation although simultaneous stimulation of both receptors exerts a clear beneficial effect. The possible relation of NR mechanism with other preconditioning mediators such as cAMP and nitric oxide synthesis are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Effect of Normothermic Recirculation is Mediated by Ischemic Preconditioning in NHBD Liver Transplantation

Net¹,

Valero²,

Almenara³

et al. 2005

American Journal of Transplantation

Self Cite

112

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“…[17][18][19][20] Countless other preconditioning regimens have been successfully tested under laboratory conditions and are awaiting further investigation in the clinical setting (Box 1). [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Some authors propose that lowdose tacrolimus reduces IRI. 36,37 Results of a multicentre randomized controlled trial on ex vivo tacrolimus perfusion are expected in 2015.…”

Section: Pretreatment Measuresmentioning

confidence: 98%

“…Preconditioning with fructose, 21 all-trans retinoic acid, 22 α-lipoic acid, 23 calcitonin gene-related peptide, 24 a cannabinoid-2 receptor agonist, 25 diazoxide (a potassium channel activator), 26 erythropoietin, 27 taurin, 28 curcumin, 29 simvastatin, 29 melatonin, 30 deferoxamine, 31 pentoxyphylline, 31 IL-10, 32 HMGB1 (high mobility group protein B1), 33 S-adenosyl methionine 34 and S-nitroso-N-acetylcysteine 35 have been shown to exert protective effect in animal models under defined laboratory conditions. and reliable approach of static cold storage became the general preservation method.…”

Section: Box 1 | Preconditioning Regimens Tested In Animal Modelsmentioning

confidence: 99%

Advances in the management of the explanted donor liver

Nebrig

Pascher

2014

Nat Rev Gastroenterol Hepatol

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Liver transplantation is the best therapy in end-stage liver disease. Donor organ shortage and efforts to expand the donor organ pool are permanent issues given that advances in perioperative management and immunosuppressive therapy have brought the procedure into widespread clinical use. The management of organ procurement, including donor preconditioning and adequate organ storage, has a key role in transplantation. However, the organ procurement process can differ substantially between transplant centres, depending on local and national preferences. Advances in the field have come from experimental and clinical research on dynamic storage systems, such as machine perfusion devices, as an alternative to static cold storage. Determination of the clinical significance of these new systems is a topic worthy of future investigations.

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“…Evidence is mounting that the inability of the liver to maintain or regain energy balance during and after surgery is one of the strongest predictors of liver damage and adverse outcome [3,4] . Also, release from injured tissue of metabolites, such as adenosine, with cardiovascular effects may further compromise the anesthetic management of seriously ill or injured patients.…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

Isoflurane preserves energy balance in isolated hepatocytes during in vitro anoxia/reoxygenation

Yu²,

Zhou³

et al. 2005

WJG

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Abstract Abstract Abstract AIM:To investigate the protective effect of isoflurane on energy balance in isolated hepatocytes during in vitro anoxia/reoxygenation, and to compare isoflurane with halothane. METHODS:Hepatocytes freshly isolated from fed rats were suspended in Krebs-Henseleit buffer, and incubated in sealed flasks under O 2 /CO 2 or N 2 /CO 2 (95%/5%, V/V) for 30 or 60 min, followed by 5 or 10 min of reoxygenation, with an added volatile anesthetic or not. ATP, ADP, and adenosine monophosphate in hepatocytes were determined by high performance liquid chromatography, and energy charge was calculated. RESULTS:During 30 min of anoxia, the energy charge and total adenine nucleotide steadily increased with the isoflurane dose from 0 to 2 minimum alveolar anesthetic concentration (MAC), then decreased from 2 to 3 MAC. In short incubations (30-35 min) at 1 MAC isoflurane, energy charge modestly decreased during anoxia, which was partially prevented by isoflurane and completely reversed by reoxygenation, and total adenine nucleotide did not decrease. In long incubations (60-70 min), both energy charge and total adenine nucleotide greatly decreased during anoxia, with partial and no reversal by reoxygenation, respectively. Isoflurane partly prevented decreases in both energy charge and total adenine nucleotide during anoxia and reoxygenation. In addition, 1 MAC isoflurane obviously increased ATP/ADP, which could not be changed by 1 MAC halothane. CONCLUSION:Isoflurane partially protects isolated hepatocytes against decreases in both energy charge and total adenine nucleotide during short (reversible) or long (irreversible) anoxia. INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTIONHepatic anoxia, alone or as a component of ischemia, is an ever-present concern during abdominal surgery, because associated inhibition of energy supply threatens liver cell function and viability [1,2] . Evidence is mounting that the inability of the liver to maintain or regain energy balance during and after surgery is one of the strongest predictors of liver damage and adverse outcome [3,4] . Also, release from injured tissue of metabolites, such as adenosine, with cardiovascular effects may further compromise the anesthetic management of seriously ill or injured patients. Thus, surgeons and anesthesiologists need to be aware of, and to use, whatever measures are available to preserve energy balance in tissues.The sum of ATP splitting by many concurrent energyrequiring reactions is called "ATP demand." ATP supply occurs mainly via mitochondrial oxidative phosphorylation, which is absolutely dependent on O 2 . Under normal conditions, ATP supply easily keeps pace with ATP demand, and adenine nucleotide (high-energy phosphate) exists mainly in the form of ATP, along with relatively small amounts of ADP and adenosine monophosphate (AMP). However, when ATP supply is inhibited by lack of oxygen, ATP demand predominates, ADP and AMP then accumulate at the expense of ATP, and eventually adenosine and oth...

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Hepatic preconditioning after prolonged warm ischemia by means of S-adenosyl-L-methionine administration in pig liver transplantation from non-heart-beating donors

Abstract: SAMe administration during liver procurement from NHBDs prevents liver endothelial, parenchymal, and biliary tract damage. The protective role of SAMe may be partially mediated by the effect of adenosine during liver procurement.

Cited by 31 publications

References 30 publications

The Effect of Normothermic Recirculation is Mediated by Ischemic Preconditioning in NHBD Liver Transplantation

The Effect of Normothermic Recirculation is Mediated by Ischemic Preconditioning in NHBD Liver Transplantation

Advances in the management of the explanted donor liver

Isoflurane preserves energy balance in isolated hepatocytes during in vitro anoxia/reoxygenation

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