Reduced Oxidative Stress During Acellular Reperfusion of the Rat Liver After Hypothermic Oscillating Perfusion

Dutkowski, P.; Schönfeld, S.; Heinrich, Theresa; Watzka, Matthias; Winkelbach, V.; Krysiak, Małgorzata; Odermatt, Benjamin; Junginger, T

doi:10.1097/00007890-199907150-00009

Cited by 26 publications

(20 citation statements)

References 24 publications

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“…A modified UW solution for machine perfusion was used as described previously, omitting hydroxyethyl starch to reduce viscosity (6). Cold storage was performed with standard UW solution.…”

Section: Methodsmentioning

confidence: 99%

“…The animals were anesthetized with ether and the liver was exposed through a midline incision. The liver was cannulated, flushed and resected as previously described (6,11).…”

Section: Animalsmentioning

confidence: 99%

“…Glykolytic metabolites: Liver glycogen, ATP, ADP, AMP, energy charge and lactate were determined according to earlier studies (6,11): for analysis of nucleotides livers were homogenated (1:10) in cold 4% HClO 4 with a Potter teflon homogenizer. After centrifugation and pH adjusting (pH 8.5) ATP was measured by UV spectroscopy (340 nm) with hexokinase and glucose-6-phosphate dehydrogenase.…”

Section: Assessment Of Hepatocyte Cell Injurymentioning

confidence: 99%

“…Although only minor morphological alterations are known during the first 10 h of cold rat liver storage with UW solution (25), a number of studies clearly demonstrated severe metabolite depletion already during short periods of cold static preservation, for example, significant ATP depletion and energy charge depletion of hepatic tissue were reported after only 1 h of cold storage (6). The amount of cellular free chelatable iron in isolated rat hepatocytes increased after 30 min of cold preservation and stayed at this level for 6 h (13).…”

Section: Dutkowski Et Almentioning

confidence: 99%

“…Experiments on the isolated perfused rat liver (IPRL) suggested that a corrected ATP loss before rewarming could help the liver to overcome reperfusion injury (4,6). Several groups could restore the energy reserve and components of the cellular redox system through the use of machine liver perfusion systems under either hypothermic (7,8) or normothermic (9,10) conditions, but these models have been challenged and found unattractive by many due to the complexity of the proposed system and the need to run machine perfusion during cold or warm preservation.…”

Section: Introductionmentioning

confidence: 99%

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Rescue of the Cold Preserved Rat Liver by Hypothermic Oxygenated Machine Perfusion

Dutkowski

Graf

Clavien

2006

American Journal of Transplantation

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106

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The aim of the study was to investigate whether hypothermic oxygenated liver perfusion after cold liver preservation resuscitated metabolic parameters and whether this treatment had a benefit for liver viability upon reperfusion.We preserved rat livers either by cold storage (UW) for 10 h, or by perfusion for 3 h (oxygenated modified UW) after 10 h cold storage. We assessed viability of livers after preservation and after ischemic rewarming + normothermic reperfusion ex vivo. Ten hour cold storage reduced mitochondrial cytochrome oxidase and metabolically depleted the livers. Oxygenated perfusion after cold storage resulted in uploaded cellular energy charge and oxidized mitochondrial cytochrome oxidase. Reperfusion after 10 h cold storage increased formation of superoxid anions, release of cytosolic LDH, lipid peroxidation, caspase activities and led to disruption of sinusoidal endothelial cells. In contrast, reperfusion after 10 h cold storage + 3 h hypothermic oxygenated perfusion resulted in no changes of lipid peroxidation, bile flow, energy charge, total glutathione, LDH release and of caspase activation, as compared to fresh resected livers. This study demonstrates, that a metabolically depleted liver due to cold storage can be energy recharged by short-termed cold machine perfusion. The machine perfused graft exhibited improved viability and functional integrity.

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“…A modified UW solution for machine perfusion was used as described previously, omitting hydroxyethyl starch to reduce viscosity (6). Cold storage was performed with standard UW solution.…”

Section: Methodsmentioning

confidence: 99%

“…The animals were anesthetized with ether and the liver was exposed through a midline incision. The liver was cannulated, flushed and resected as previously described (6,11).…”

Section: Animalsmentioning

confidence: 99%

Section: Assessment Of Hepatocyte Cell Injurymentioning

confidence: 99%

Section: Dutkowski Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rescue of the Cold Preserved Rat Liver by Hypothermic Oxygenated Machine Perfusion

Dutkowski

Graf

Clavien

2006

American Journal of Transplantation

Self Cite

106

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Oxygenation during hypothermic rat liver preservation: An in vitro slice study to demonstrate beneficial or toxic oxygenation effects

et al. 2005

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Hypothermic machine perfusion (HMP) of abdominal organs is shown to be superior compared to cold storage. However, the question remains if oxygenation is required during preservation as oxygen is essential for energy resynthesis but also generates toxic reactive oxygen species (ROS). To determine if oxygenation should be used during HMP, urea-synthesis rate, adenosine triphosphate (ATP), and generation of ROS were studied in an in vitro model, modeling ischemia-reperfusion injury. Furthermore, expression of uncoupling protein-2 (UCP-2) mRNA was assessed since UCP-2 is a potentially protective protein against ROS. Rat liver slices were preserved for 0, 24, and 48 hr in University of Wisconsin machine perfusion solution (UW-MP) with 0%, 21%, or 95% oxygen at 0 -4°C and reperfused for 24 hours. In the 0% and 95% groups, an increase of ROS was found after cold storage in UW-MP. After slice reperfusion, only the 0% oxygen group showed higher levels. The 0% group showed a lower urea-synthesis rate as well as lower ATP levels. mRNA upregulation of UCP-2 was, in contrast to kidney mRNA studies, not observed. In conclusion, oxygenation of UW-MP gave better results. This study also shows that ROS formation occurs during hypothermic preservation and the liver is not protected by UCP-2. We conclude that saturation of UW-MP with 21% oxygen allows optimal preservation results. (Liver Transpl 2005; 11:1403-1411.)

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Hypothermic liver perfusion

Schlegel

Dutkowski

2015

Liver Transpl

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Reduced Oxidative Stress During Acellular Reperfusion of the Rat Liver After Hypothermic Oscillating Perfusion

Cited by 26 publications

References 24 publications

Rescue of the Cold Preserved Rat Liver by Hypothermic Oxygenated Machine Perfusion

Rescue of the Cold Preserved Rat Liver by Hypothermic Oxygenated Machine Perfusion

Oxygenation during hypothermic rat liver preservation: An in vitro slice study to demonstrate beneficial or toxic oxygenation effects

Hypothermic liver perfusion

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