Improved machine perfusion preservation of the non-heart-beating donor rat liver using polysol: A new machine perfusion preservation solution

Bessems, Maud; Doorschodt, Benedict M.; Marle, J. van; Vreeling, Heleen; Meijer, Alfred J.; Gulik, Thomas M. van

doi:10.1002/lt.20502

Cited by 59 publications

(35 citation statements)

References 42 publications

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“…5 and Table 6 simulate most closely the conditions of continuous hypothermic perfusion. The optimal preservation solutions for effective machine perfusion have not yet been established and modifications have recently been proposed [32][33][34][35][36]. Based on our data, we would suggest to include an iron chelator into these solutions and, in addition, to replace histidine by less toxic derivatives such as Nα-acetyl-L-histidine.…”

Section: Discussionmentioning

confidence: 87%

Histidine-induced injury to cultured liver cells, effects of histidine derivatives and of iron chelators

Rauen

Klempt

Groot

2006

Cell. Mol. Life Sci.

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The amino acid histidine is an excellent buffer and is therefore included in several organ preservation solutions used in transplantation medicine. However, when used at concentrations as in these solutions, histidine has a marked injurious potential. Therefore, we here assessed the mechanism of histidine-induced cell injury and searched for ways to use the buffering power of histidine but avoid histidine toxicity. When cultured hepatocytes were incubated in HTK solution or in modified Krebs-Henseleit buffer containing 198 mM L-histidine at 37 degrees C, most cells lost viability within 3 h (LDH release 86 +/- 7% and 89 +/- 5%, respectively). This injury was accompanied by marked lipid peroxidation, and was strongly inhibited by hypoxia, by the antioxidants trolox, butylated hydroxytoluene and N-acetylcysteine and by the membrane-permeable iron chelators 2,2'-dipyridyl, 1,10-phenanthroline, LK 614, LK 616 and deferoxamine. Thus, histidine-induced cell injury appears to be mediated by an iron-dependent formation of reactive oxygen species. D-Histidine, imidazol and L-histidine methyl ester also elicited marked injury, while the N-substituted derivatives Nalpha-acetyl-L-histidine and tert-butyl-oxycarbonylhistidine and histidine-containing dipeptides showed almost no toxicity. Histidine toxicity, its iron dependence and the superiority of Nalpha-acetyl-L-histidine were also evident during/after cold (4 degrees C) incubations. Therefore, we suggest the addition of iron chelators to histidine-containing solutions, and/or replacing histidine with Nalpha-acetyl-L-histidine in organ preservation solutions.

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Section: Discussionmentioning

confidence: 87%

Histidine-induced injury to cultured liver cells, effects of histidine derivatives and of iron chelators

Rauen

Klempt

Groot

2006

Cell. Mol. Life Sci.

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“…A critical evaluation of the functional conditions used in the IPPK model is necessary to assess its usefulness, reliability and reproducibility. Here, we compared three different perfusion and oxygenation methods that have previously been described in the literature [6,9,15]: flow-controlled reperfusion with pure oxygen and pressure-controlled reperfusion with pure oxygen or carbogen. Before reperfusion, the kidneys were retrieved with intact circulation and cold-stored for 24 h in the widely employed HTK solution, which has shown posttransplant outcomes comparable to those of other preservation solutions, such as University of Wisconsin solution, in most clinical trials [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…For oxygenation of the perfusate, pure oxygen and carbogen (95% O 2 /5% CO 2 ) have been employed [1,3,6,10,11,12,13,15,16,17]. Since both blood and KHB contain sodium bicarbonate as their buffering agent, which requires CO 2 to exert its function, oxygenation with carbogen seems to offer advantages over pure oxygen [18].…”

Section: Introductionmentioning

confidence: 99%

Determination of the Preferred Conditions for the Isolated Perfusion of Porcine Kidneys

Mancina¹,

Kalenski²,

Paschenda³

et al. 2014

Eur Surg Res

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Background: The isolated perfused porcine kidney (IPPK) model has been the method of choice for the early preclinical evaluation of kidney graft preservation techniques. The preferred reperfusion conditions have not yet been determined. Here, we examined the effects of pressure- or flow-controlled perfusion and oxygenation by pure oxygen or carbogen (95% O₂/5% CO₂) on normothermic reperfusion in the IPPK model. Methods: Porcine kidneys were cold-stored for 24 h in histidine-tryptophan-ketoglutarate solution and reperfused for 1 h with normothermic whole blood/Krebs-Henseleit buffer medium (20/80%). Kidneys (n = 5/group) were flow-controlled reperfused with pure oxygen (1 ml/min/g; Flow-O₂) or pressure-controlled reperfused (85 mm Hg mean arterial pressure) and oxygenated with either pure oxygen (Pressure-O₂) or carbogen (Pressure-O₂/CO₂). Renal function and damage were assessed during reperfusion and NGAL and HIF-1α levels were analyzed using an ELISA. Results: Pressure-O₂ and Pressure-O₂/CO₂ were associated with significantly better renal hemodynamics and acid-base homeostasis compared to Flow-O₂. Urine protein concentrations and the fractional excretion of sodium were lower with both Pressure-O₂ and Pressure-O₂/CO₂ than with Flow-O₂. NGAL and HIF-1α levels were also lower with Pressure-O₂ and Pressure-O₂/CO₂ than with Flow-O₂. Only Pressure-O₂/CO₂ could demonstrate a significantly increased urine production compared to Flow-O₂. The structural integrity was well preserved in the Pressure-O₂ and Pressure-O₂/CO₂ groups, whereas diffuse and global glomerular destruction was observed in the Flow-O₂ group. Conclusion: In the IPPK model, the application of pressure-controlled reperfusion with carbogen oxygenation, and to a lesser extent with pure oxygen, maintained physiological renal function for 1 h, thus providing a reliable and reproducible ex vivo evaluation of kidney preservation quality.

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“…The method of preserving these organs is more critical than that required for living donor organs [37]. The livers from DCD donors represent a potential pool of hepatocytes and could be a new source for HTx in the near future.…”

Section: Discussionmentioning

confidence: 99%

Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function

Murakami²,

Aoki³

et al. 2015

Eur Surg Res

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Background: Cell therapy, such as hepatocyte transplantation (HTx), is promising for the treatment of metabolic liver diseases or as a bridge to orthotopic liver transplantation in patients with fulminant liver failure. However, one of the limitations of this therapy is the shortage of donors. The present study aims to investigate whether the two-layer method (TLM) of cold preservation with oxygenation improves the viability and activity of hepatocytes from rat donation after cardiac death (DCD) donors compared with results obtained with the University of Wisconsin (UW) solution. Moreover, we evaluated the hepatocyte function after culture or transplantation into the spleen. Materials and Methods: We used male Sprague-Dawley rats for this study. The DCD model was induced by phrenotomy after injecting heparin. We assigned rats based on warm ischemia times of 15 and 30 min to groups S and L, respectively. Each group (n = 5) was then subdivided as follows: (1) group S: not preserved (S/N), preserved by TLM for 3 h (S/TLM3) and 12 h (S/TLM12), and in the UW solution for 3 h (S/UW3) and 12 h (S/UW12), and (2) group L: not preserved (L/N), preserved by TLM for 3 h (L/TLM3) and 12 h (L/TLM12), and in the UW solution for 3 h (L/UW3) and 12 h (L/UW12). The cell viability and function of isolated DCD hepatocytes were analyzed for culture or HTx into the spleen. Results: The viability and ATP levels of DCD hepatocytes significantly improved after TLM compared with the values after preservation in cold UW solution in group S/N (p < 0.059). The levels of albumin production and urea synthesis by hepatocytes after culture were significantly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12 (p < 0.05), respectively. Further, serum albumin levels after HTx were also markedly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12. The morphological features revealed that cultured and transplanted hepatocytes remained clearly viable and maintained an expression for specific hepatic function, such as the production of albumin and glycogen. Conclusion: This novel method of oxygenated cold preservation of DCD livers can expand the hepatocyte donor pool for HTx and establish a wider application of this developing technique.

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Improved machine perfusion preservation of the non-heart-beating donor rat liver using polysol: A new machine perfusion preservation solution

Cited by 59 publications

References 42 publications

Histidine-induced injury to cultured liver cells, effects of histidine derivatives and of iron chelators

Histidine-induced injury to cultured liver cells, effects of histidine derivatives and of iron chelators

Determination of the Preferred Conditions for the Isolated Perfusion of Porcine Kidneys

Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function

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