End‐ischemic reconditioning of liver allografts: Controlling the rewarming

Hoyer, Dieter P.; Paul, Andreas; Luer, Sebastian; Reis, Henning; Efferz, Patrik; Minor, Thomas

doi:10.1002/lt.24515

Cited by 33 publications

(37 citation statements)

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“…Further experiments have indicated that rewarming of the organ during oxygenated machine perfusion could further contribute to improved organ integrity and in vivo functionality through an adapted increase in metabolic activity of mitochondria and tissue cells . Controlled oxygenated rewarming (COR) to 20°C was already shown to have protective capacities and improves organ recovery upon reperfusion …”

Section: Introductionmentioning

confidence: 99%

“…9 Further experiments have indicated that rewarming of the organ during oxygenated machine perfusion could further contribute to improved organ integrity and in vivo functionality through an adapted increase in metabolic activity of mitochondria and tissue cells. 10 Controlled oxygenated rewarming (COR) to 20°C was already shown to have protective capacities and improves organ recovery upon reperfusion. 11 So far, extracorporeal temperature rise during COR had been limited to 20°C, as perfusion solutions had been used that were specifically designed for organ protection at hypothermia and might become inappropriate perfusates at increasing temperatures.…”

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confidence: 99%

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Controlled oxygenated rewarming up to normothermia for pretransplant reconditioning of liver grafts

Horn

Baba

Hannaert

et al. 2017

Clinical Transplantation

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Controlled oxygenated rewarming (COR) up to 20°C during ex vivo machine perfusion limits reperfusion-induced tissue injury upon graft implantation. Rewarming up to normothermia might add further benefits and provide better prediction of posttransplantation organ function. The effect of 90 minutes of oxygenated machine perfusion with Aqix RS-I after cold storage combined with gentle rewarming up to 20°C (COR20) or 35°C (COR35) was studied in rat livers and compared with cold storage alone (CS, n = 6, resp). Postpreservation recovery was evaluated upon warm reperfusion using an established in vitro system. COR generally resulted in significantly improved energetic recovery, increased bile flow, less activities alanine aminotransferase (ALT) release, and improved histopathology upon reperfusion as compared to only cold-stored livers, without significant differences between COR20 and COR35.Parameters obtained during COR, especially during COR35, also allowed for prediction of hepatic recovery upon reperfusion. For instance, ulterior bile production upon reperfusion was found closely correlated to bile flow observed already during COR35 (R 2 = 0.91). COR significantly improved liver quality after static cold storage. Elevation of machine perfusion temperature up to 35°C may prove promising to refine ex vivo evaluation of the graft prior to transplantation. K E Y W O R D Scontrolled oxygenated rewarming, liver preservation, machine perfusion, organ reconditioning | INTRODUCTIONOne of the major restrictions in transplantation medicine is the limited number of available donor organs. Due to this imbalance between donor organs and waiting recipients, the criteria of organ selection were extended and grafts of lesser quality became increasingly accepted to be transplanted. 1 The use of these "less-than-optimal" grafts provides new challenges in transplantation research with regard to organ preservation and conditioning. 2 New ex vivo strategies for maintenance and improvement of organ function could prevent storage and reperfusion-induced tissue injury and could therefore result in decreased post-transplantation graft dys-or nonfunction. 3Organ preservation traditionally includes flush-out with appropriate preservation solutions followed by cold storage under hypoxic conditions. 4 Problems associated with this technique are hypoxiainduced apoptotic events as well as activation of pro-inflammatory mediators, which influence post-transplantation organ function and integrity. 5 Previous research evidenced that main destructive effects rather establish during exposure of organs to blood circulation after implantation than during the ischemic cold storage period itself. 6This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Controlled oxygenated rewarming up to normothermia for pretransplant reconditioning of liver grafts

Horn

Baba

Hannaert

et al. 2017

Clinical Transplantation

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“…These unexpected results compared to the UK trial was speculated to be related to the higher proportion of DCD livers (44% Edmonton trial versus 20% for UK or Toronto trials) or the prolonged cold ischemia time (median, 2 hours 47 minutes) due to uncommonly complex back‐table reconstructions, and HTK donor flush in the Edmonton trial. Additionally, the superiority of COR and SNMP in porcine livers sparked the first successful application or COR in clinical liver transplantation . Rewarming therapies, the newest methodology in machine preservation, may become the ultimate compromise with their ability to capture advantages of relative convenience as compared with NMP, longevity of storage comparable to HMP or SCS, optimal resuscitation in predictive animal models, and predictive ex vivo assessment prior to transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Others found that gradual increase of perfusate flow and oxygen throughout the rewarming period minimized AST/ALT production . Controlled oxygenated rewarming (COR) perfusion was also shown to be superior in recovering energy stores and minimizing hepatocellular and mitochondrial stores after 18 hours of CS as compared with NMP …”

Section: Normothermic Machine Perfusion Settingsmentioning

confidence: 99%

Liver ex situ machine perfusion preservation: A review of the methodology and results of large animal studies and clinical trials

Marecki¹,

Bozorgzadeh²,

Porte

et al. 2017

Liver Transpl

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Ex vivo machine perfusion (MP) is a promising way to better preserve livers prior to transplantation. Currently, no methodology has a verified benefit over simple cold storage. Before becoming clinically feasible, MP requires validation in models that reliably predict human performance. Such a model has been found in porcine liver, whose physiological, anatomical, and immunological characteristics closely resemble the human liver. Since the 1930s, researchers have explored MP as preservation, but only recently have clinical trials been performed. Making this technology clinically available holds the promise of expanding the donor pool through more effective preservation of extended criteria donor (ECD) livers. MP promises to decrease delayed graft function, primary nonfunction, and biliary strictures, which are all common failure modes of transplanted ECD livers. Although hypothermic machine perfusion (HMP) has become the standard for kidney ex vivo preservation, the precise settings and clinical role for liver MP have not yet been established. In research, there are 2 schools of thought: normothermic machine perfusion, closely mimicking physiologic conditions, and HMP, to maximize preservation. Here, we review the literature for porcine ex vivo MP, with an aim to summarize perfusion settings and outcomes pertinent to the clinical establishment of MP. Liver Transplantation 23 679-695 2017 AASLD.

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“…Recent experiments are suggesting that the protective effect of hypothermic machine perfusion can be further enhanced by a controlled oxygenated rewarming (COR) and, after preceding cold preservation, the controlled rewarming resulted in significantly better organ recovery than abrupt perfusion with warm perfusate .…”

Section: Introductionmentioning

confidence: 99%

Prediction of renal function upon reperfusion by ex situ controlled oxygenated rewarming

Minor

Sutschet

Witzke³

et al. 2016

Eur J Clin Investigation

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BackgroundPost‐transplant function of suboptimal kidney grafts can be improved but not accurately predicted by hypothermic machine perfusion. Therefore, a new concept of ex situ pre‐implantation machine perfusion with controlled rewarming up to subnormothermic temperatures was developed and evaluated.Materials and methodsPorcine kidneys (n = 6/group) were retrieved before or 30 min after cardiac arrest of the donor and subjected to 18 h of static cold storage. In some cases, 90 min of machine‐controlled oxygenated rewarming (COR) was added thereafter. Functional integrity was evaluated in all kidneys by subsequent normothermic reperfusion in vitro. After supplementation of the preservation solution (Custodiol‐N solution + 5 g/L dextran 40) with 10 mg/dL creatinine, ex situ renal function was assessed by monitoring urine output, urinary creatinine and creatinine clearance at 20 °C. Functional integrity was evaluated in all kidneys by normothermic reperfusion.Results COR resulted in a more than twofold improvement of postreperfusion creatinine clearance, oxygen consumption and enzyme release upon reperfusion, when compared with static cold storage. Predictive discrimination between kidneys with good or impaired function upon reperfusion based on parameters during perfusion at 4 °C was only moderate. This improved significantly at 20 °C. Correlation with renal clearance upon reperfusion was weak for vascular resistance at 8° (r 2 = 0·2) and 20 °C (r 2 = 0·41). Best correlation was found for clearance measurements at 20° (r 2 = 0·81).ConclusionsReconditioning by controlled oxygenated rewarming up to 20 °C improves renal function after reperfusion and can be utilized to assess graft integrity of predamaged donor kidneys.

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End‐ischemic reconditioning of liver allografts: Controlling the rewarming

Cited by 33 publications

References 40 publications

Controlled oxygenated rewarming up to normothermia for pretransplant reconditioning of liver grafts

Controlled oxygenated rewarming up to normothermia for pretransplant reconditioning of liver grafts

Liver ex situ machine perfusion preservation: A review of the methodology and results of large animal studies and clinical trials

Prediction of renal function upon reperfusion by ex situ controlled oxygenated rewarming

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