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Ursula Rauen - One of the best experts on this subject based on the ideXlab platform.
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a new Preservation Solution for lung transplantation evaluation in a porcine transplantation model
Journal of Heart and Lung Transplantation, 2012Co-Authors: N Pizanis, Andrey V Petrov, J Heckmann, Ingrid Wiswedel, Jeremias Wohlschlager, Herbert De Groot, Heinz Jakob, Ursula Rauen, Markus KamlerAbstract:Background Lung Preservation injury is still a major problem in lung transplantation. The aim of the current study was to evaluate the effects of a new Preservation Solution (Custodiol-N) for lung Preservation. Methods Using an in vivo pig model, 7 lungs each were preserved for 24 hours after perfusion with: low-potassium dextran (LPD) Solution as control (Group I); base Solution of Custodiol-N without iron chelators (Group II); Custodiol-N (Group III); or Custodiol-N supplemented with dextran 40 (Group IV). Four animals received a sham operation. After left lung transplantation and contralateral lung exclusion, hemodynamics and blood gases were monitored for 6 hours; tissue samples were taken at the end of the experiments. Results All animals survived the transplantation procedure. Base Solution– and Custodiol-N–preserved lungs (Groups II and III) showed graft function similar to that of LPD-preserved lungs (Group I), showing a trend toward improved values. Custodiol-N with dextran (Group IV) led to a significant reduction of mean pulmonary arterial pressure (20 ± 2 vs 28 ± 3 mm Hg, p 5 , p p 2 values were significantly lower (51 ± 9 vs 77 ± 5 mm Hg at 6 hours, p Conclusions Custodiol-N Solution is a new alternative Preservation Solution for lung transplantation that offers significantly superior protection compared with LPD when dextran 40 is added.
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prolonged cold storage using a new histidine tryptophan ketoglutarate based Preservation Solution in isogeneic cardiac mouse grafts
European Heart Journal, 2011Co-Authors: Tobias R Turk, Ingrid Wiswedel, Herbert De Groot, Ursula Rauen, Thorsten Feldkamp, Hideo A Baba, Andreas Kribben, Oliver WitzkeAbstract:Aims The aim of this study was to evaluate a new histidine–tryptophan–ketoglutarate (HTK)-based cold Preservation Solution in comparison with traditional HTK Solution in a mouse cardiac transplant model and to assess the impact of chloride ions and of iron chelators. Methods and results After 24 h cold ischaemia, traditional HTK-preserved hearts survived up to 13 days (4.4 ± 1.7 days; n = 8)). Hearts stored in the new Solution without iron chelators (N46) showed significantly prolonged survival up to 2 months (N46: 11.9 ± 8.7 days; P < 0.01; n = 7) and with iron chelators (DesfLK) up to 3 months (N46 DesfLK: 12.7 ± 13.7 days; n = 6). Re-beating time was significantly shorter with the new Solution (HTK: 14.5 ± 5.9 min, N46: 9.2 ± 2.7 min, N46 DesfLK: 7.1 ± 3.7 min; P < 0.01). The new Solution showed significantly decreased release of creatine kinase (HTK: 25998 ± 8471 U/L, N46: 13829 ± 7679 U/L, N46 DesfLK: 3093 ± 597 U/L; P < 0.01 and n = 7 each) and lactate dehydrogenase (HTK: 5391 ± 1062 U/L, N46: 3428 ± 1890 U/L, P < 0.05; N46 DesfLK: 682 ± 344 U/L, P < 0.01) and decreased histological evidence of injury. A chloride-poor variant of the new Solution showed inferior graft survival. Conclusion The new Solution markedly attenuates myocardial injury and yields better graft survival than traditional HTK Solution. The presence of chloride ions is crucial for heart Preservation. Some protective effects are obviously caused by iron chelators.
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improvement of the cold storage of blood vessels with a vascular Preservation Solution study in porcine aortic segments
Journal of Vascular Surgery, 2008Co-Authors: Timo Wille, Herbert De Groot, Ursula RauenAbstract:Background Cold-induced injury to various cell types has been shown to be mediated predominantly by chelatable iron. For endothelial cells, this type of injury has so far only been shown in cultured cells. Hypothesizing that this iron-dependent cold-induced injury might also occur in the endothelium of intact vessels, we here set out to optimize the hypothermic storage of blood vessels. Methods Segments of porcine aorta were stored for 2 to 21 days in histidine-tryptophan-ketoglutarate (HTK) Solution or in modified Solutions with or without the iron chelators deferoxamine or LK 614 at 4°C. Parts of the segments were assayed immediately after cold storage, the other parts after subsequent rewarming. The percentage of dead (propidium iodide-positive) endothelial cells was assessed by "intravital" fluorescence microscopy, mitochondrial membrane potential was assessed by laser scanning microscopy after staining with tetramethylrhodamine methyl ester (TMRM) and thrombocyte adhesion was studied using 5-(and -6)-carboxy SNARF-1-stained thrombocytes. Results The endothelium of porcine aortic segments sustained moderate injury during the cold incubation itself, but major injury during rewarming. The addition of the iron chelator deferoxamine (1 mmol/L) significantly inhibited cold-induced endothelial cell injury irrespective of the Solution used for cold storage (eg, 14 days of cold storage + 3 hours rewarming: HTK 66 ± 7%, HTK + 1 mmol/L deferoxamine 40 ± 10% propidium iodide-positive endothelial cells). An amino acid (glycine, alanine, aspartate)-containing base Solution with N-acetylhistidine as buffer was optimized. The optimized base Solution with pH 7.0 and potassium and chloride as main ions yielded a further decrease of endothelial cell injury. Combination of deferoxamine (in lower concentration, ie, 0.1 mmol/L) with the new, more membrane-permeable iron chelator LK 614 (20 μmol/L) further improved Preservation so that even after 3 weeks of cold storage plus 3 hours rewarming only 10 ± 1% of endothelial cells were propidium iodide positive. In this optimized Solution, both endothelial cell survival and mitochondrial membrane potential were significantly better preserved than in the clinically used Solutions HTK, University of Wisconsin (UW) and Perfadex, or in physiological saline. Thrombocyte adhesion was also significantly reduced after cold storage in the optimized Solution compared with HTK Solution. Conclusion Cold-induced injury to the endothelium of porcine aortic segments is, as the injury to cultured endothelial cells, mediated by chelatable iron. Thus, iron chelators, but also optimized base Solutions, are options to improve the storage of vascular endothelium. The optimized Solution should now be tested in in vivo animal experiments.
Hiroshi Date - One of the best experts on this subject based on the ideXlab platform.
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protective effects of a hydrogen rich Preservation Solution in a canine lung transplantation model
The Annals of Thoracic Surgery, 2020Co-Authors: Hidenao Kayawake, Toyofumi F Chenyoshikawa, M Saito, H Yamagishi, Akihiko Yoshizawa, Shinich Hirano, Ryosuke Kurokawa, Hiroshi DateAbstract:Abstract Background Molecular hydrogen (H2) has protective effects against ischemia-reperfusion injury in various organs. Because they are easier to transport and safer to use than inhaled H2, H2-rich Solutions are suitable for organ Preservation. In this study, we examined the protective effects of an H2-rich Solution for lung Preservation in a canine left lung transplantation (LTx) model. Methods Ten beagles underwent orthotopic left LTx after 23 hours of cold ischemia followed by reperfusion for 4 hours. Forty-five minutes after reperfusion, the right main pulmonary artery was clamped to evaluate the function of the implanted graft. The beagles were divided into two groups: control (CON group, n=5) and hydrogen (H2 group, n=5). In the CON group, the donor lungs were flushed and immersed during cold Preservation at 4°C using ET-Kyoto Solution, and in the H2 group, these were flushed and immersed using H2-rich ET-Kyoto Solution. Physiological assessments were performed during reperfusion. After reperfusion, the wet-to-dry ratios were determined, and histological examinations were performed. Results Significantly higher partial pressure of arterial oxygen and significantly lower partial pressure of carbon dioxide were observed in the H2 group than in the CON group (p=0.045 and p Conclusions Our results demonstrated that the H2-rich Preservation Solution attenuated ischemia-reperfusion injury in a canine left LTx model. (247 words)
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vascular endothelial cadherin expression after reperfusion correlates with lung injury in rat lung transplantation
The Annals of Thoracic Surgery, 2016Co-Authors: Satona Tanaka, Toyofumi F Chenyoshikawa, Ei Miyamoto, Keiji Ohata, Kyoko Hijiya, Akihiro Aoyama, Takeshi Kondo, Hideki Motoyama, Mamoru Takahashi, Hiroshi DateAbstract:Background Vascular endothelial-cadherin (VEC), composing the adherens junction of endothelial cells, has been shown to regulate vascular permeability. The aim of this study was to investigate VEC expression during cold ischemia (CI) and reperfusion and whether a dibutyryl cyclic adenosine 3′,5′-monophosphate (db-cAMP) and nitroglycerin (NTG) additive to Preservation Solution can maintain VEC. Methods Rat left lung transplantation after CI was performed, and reperfusion was done for 2 hours. The experimental groups were Control (n = 5), CI3 (n = 5), CI6 (n = 6), and CI6+AMP/NTG (n = 6) with minimum ischemic period, 3 hours and 6 hours of CI, respectively, and 6 hours of CI with db-cAMP and NTG additive to Preservation Solution, respectively. Lung mechanics, lung wet-to-dry weight ratio (W/D), and the histologic findings of the graft were evaluated. The expression of VEC was evaluated by Western blot analysis of the lung tissue lysates. Results The CI3 group showed a decrease in dynamic compliance with perivascular edema. Dynamic compliance, graft oxygenation, and W/D were substantially deteriorated, and intraalveolar edema with neutrophil infiltration was recognized in the CI6 group. They were improved in the CI6+AMP/NTG group. VEC expression was maintained during CI. After reperfusion, it reduced substantially in the CI6 group and was maintained in the CI6+AMP/NTG group. Conclusions VEC expression was maintained during CI; however, it reduced early after reperfusion after 6 hours of CI, correlating with severe intraalveolar edema. db-cAMP/NTG additive to the Preservation Solution contributed to the maintenance of VEC expression after reperfusion.
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clinical application of an extracellular phosphate buffered Solution ep tu for lung Preservation preliminary results of a japanese series
Surgery Today, 2012Co-Authors: Yoshinori Okada, Hiroshi Date, Yuji Matsumura, Toru Bando, Takahiro Oto, Tetsu Sado, Yasushi Hoshikawa, Masafumi Noda, Hisashi Oishi, Takashi KondoAbstract:Purpose We evaluated the effect of an extracellular phosphate-buffered lung Preservation Solution (EP-TU Solution) on acute postoperative graft function and recipient survival in a Japanese series of cadaveric lung transplantation.
Takashi Kondo - One of the best experts on this subject based on the ideXlab platform.
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Improving the viability of tissue-resident stem cells using an organ-Preservation Solution.
FEBS Open Bio, 2019Co-Authors: Takaya Suzuki, Yoshinori Okada, Takashi Kondo, Chiharu Ota, Naoya Fujino, Yukiko Tando, Satoshi Suzuki, Mitsuhiro Yamada, Hiroshi KuboAbstract:Human clinical specimens are a valuable source of tissue‐resident stem cells, but such cells need to be collected immediately after tissue collection. To extend the timescale for collection from fresh human samples, we developed a new extracellular fluid (ECF)‐type Preservation Solution based on a high‐sodium and low‐potassium Solution containing low‐molecular‐weight dextran and glucose, which is used for Preservation of organs for transplantation. In this study, we compared the Preservation of tissue‐resident stem cells using our ECF Solution with that using three other Solutions: PBS, Dulbecco’s modified Eagle’s medium and Euro‐Collins Solution. These Solutions represent a common buffer, a common culture medium and a benchmark organ‐Preservation Solution, respectively. Lung tissues were removed from mice and preserved for 72 h under low‐temperature conditions. Of the Solutions tested, only Preservation in the ECF‐type Solution could maintain the proliferation and differentiation capacity of mouse lung tissue‐resident stem cells. In addition, the ECF Solution could preserve the viability and proliferation of human alveolar epithelial progenitor cells when stored for more than 7 days at 4 °C. The mean viability of human alveolar type II cells at 2, 5, 8 and 14 days of low‐temperature Preservation was 90.9%, 84.8%, 85.7% and 66.3%, respectively, with no significant differences up to 8 days. Overall, our findings show that use of our ECF‐type Preservation Solution may maintain the viability and function of tissue‐resident stem cells. Use of this Preservation Solution may facilitate the investigation of currently unobtainable human tissue specimens for human stem cell biology.
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clinical application of an extracellular phosphate buffered Solution ep tu for lung Preservation preliminary results of a japanese series
Surgery Today, 2012Co-Authors: Yoshinori Okada, Hiroshi Date, Yuji Matsumura, Toru Bando, Takahiro Oto, Tetsu Sado, Yasushi Hoshikawa, Masafumi Noda, Hisashi Oishi, Takashi KondoAbstract:Purpose We evaluated the effect of an extracellular phosphate-buffered lung Preservation Solution (EP-TU Solution) on acute postoperative graft function and recipient survival in a Japanese series of cadaveric lung transplantation.
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Preservation Solution for lung transplantation
General Thoracic and Cardiovascular Surgery, 2009Co-Authors: Yoshinori Okada, Takashi KondoAbstract:Despite the increasing success of lung transplantation as the mainstay therapeutic modality for end-stage lung disease, the 1-year survival rate after lung transplantation remains 80% and primary graft dysfunction (PGD) accounts for 30% of mortality. Ischemia-reperfusion injury has been identified as one of the main causes of PGD, and thus significant efforts have been made to optimize the methods for lung Preservation in an attempt to minimize lung injury during the period of ischemia. The composition of the lung Preservation Solution used in the pulmonary artery flush has been considered to be the key to successful lung Preservation, and many lung transplant programs have been shifting the use of the Preservation Solution from the intracellular fluid type to the extracellular fluid type because of preferable posttransplant lung function with the latter. This review summarizes the experimental and clinical studies on lung Preservation, particularly focusing attention on the Preservation Solution being employed for clinical lung transplantation.
Herbert De Groot - One of the best experts on this subject based on the ideXlab platform.
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a new Preservation Solution for lung transplantation evaluation in a porcine transplantation model
Journal of Heart and Lung Transplantation, 2012Co-Authors: N Pizanis, Andrey V Petrov, J Heckmann, Ingrid Wiswedel, Jeremias Wohlschlager, Herbert De Groot, Heinz Jakob, Ursula Rauen, Markus KamlerAbstract:Background Lung Preservation injury is still a major problem in lung transplantation. The aim of the current study was to evaluate the effects of a new Preservation Solution (Custodiol-N) for lung Preservation. Methods Using an in vivo pig model, 7 lungs each were preserved for 24 hours after perfusion with: low-potassium dextran (LPD) Solution as control (Group I); base Solution of Custodiol-N without iron chelators (Group II); Custodiol-N (Group III); or Custodiol-N supplemented with dextran 40 (Group IV). Four animals received a sham operation. After left lung transplantation and contralateral lung exclusion, hemodynamics and blood gases were monitored for 6 hours; tissue samples were taken at the end of the experiments. Results All animals survived the transplantation procedure. Base Solution– and Custodiol-N–preserved lungs (Groups II and III) showed graft function similar to that of LPD-preserved lungs (Group I), showing a trend toward improved values. Custodiol-N with dextran (Group IV) led to a significant reduction of mean pulmonary arterial pressure (20 ± 2 vs 28 ± 3 mm Hg, p 5 , p p 2 values were significantly lower (51 ± 9 vs 77 ± 5 mm Hg at 6 hours, p Conclusions Custodiol-N Solution is a new alternative Preservation Solution for lung transplantation that offers significantly superior protection compared with LPD when dextran 40 is added.
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prolonged cold storage using a new histidine tryptophan ketoglutarate based Preservation Solution in isogeneic cardiac mouse grafts
European Heart Journal, 2011Co-Authors: Tobias R Turk, Ingrid Wiswedel, Herbert De Groot, Ursula Rauen, Thorsten Feldkamp, Hideo A Baba, Andreas Kribben, Oliver WitzkeAbstract:Aims The aim of this study was to evaluate a new histidine–tryptophan–ketoglutarate (HTK)-based cold Preservation Solution in comparison with traditional HTK Solution in a mouse cardiac transplant model and to assess the impact of chloride ions and of iron chelators. Methods and results After 24 h cold ischaemia, traditional HTK-preserved hearts survived up to 13 days (4.4 ± 1.7 days; n = 8)). Hearts stored in the new Solution without iron chelators (N46) showed significantly prolonged survival up to 2 months (N46: 11.9 ± 8.7 days; P < 0.01; n = 7) and with iron chelators (DesfLK) up to 3 months (N46 DesfLK: 12.7 ± 13.7 days; n = 6). Re-beating time was significantly shorter with the new Solution (HTK: 14.5 ± 5.9 min, N46: 9.2 ± 2.7 min, N46 DesfLK: 7.1 ± 3.7 min; P < 0.01). The new Solution showed significantly decreased release of creatine kinase (HTK: 25998 ± 8471 U/L, N46: 13829 ± 7679 U/L, N46 DesfLK: 3093 ± 597 U/L; P < 0.01 and n = 7 each) and lactate dehydrogenase (HTK: 5391 ± 1062 U/L, N46: 3428 ± 1890 U/L, P < 0.05; N46 DesfLK: 682 ± 344 U/L, P < 0.01) and decreased histological evidence of injury. A chloride-poor variant of the new Solution showed inferior graft survival. Conclusion The new Solution markedly attenuates myocardial injury and yields better graft survival than traditional HTK Solution. The presence of chloride ions is crucial for heart Preservation. Some protective effects are obviously caused by iron chelators.
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improvement of the cold storage of blood vessels with a vascular Preservation Solution study in porcine aortic segments
Journal of Vascular Surgery, 2008Co-Authors: Timo Wille, Herbert De Groot, Ursula RauenAbstract:Background Cold-induced injury to various cell types has been shown to be mediated predominantly by chelatable iron. For endothelial cells, this type of injury has so far only been shown in cultured cells. Hypothesizing that this iron-dependent cold-induced injury might also occur in the endothelium of intact vessels, we here set out to optimize the hypothermic storage of blood vessels. Methods Segments of porcine aorta were stored for 2 to 21 days in histidine-tryptophan-ketoglutarate (HTK) Solution or in modified Solutions with or without the iron chelators deferoxamine or LK 614 at 4°C. Parts of the segments were assayed immediately after cold storage, the other parts after subsequent rewarming. The percentage of dead (propidium iodide-positive) endothelial cells was assessed by "intravital" fluorescence microscopy, mitochondrial membrane potential was assessed by laser scanning microscopy after staining with tetramethylrhodamine methyl ester (TMRM) and thrombocyte adhesion was studied using 5-(and -6)-carboxy SNARF-1-stained thrombocytes. Results The endothelium of porcine aortic segments sustained moderate injury during the cold incubation itself, but major injury during rewarming. The addition of the iron chelator deferoxamine (1 mmol/L) significantly inhibited cold-induced endothelial cell injury irrespective of the Solution used for cold storage (eg, 14 days of cold storage + 3 hours rewarming: HTK 66 ± 7%, HTK + 1 mmol/L deferoxamine 40 ± 10% propidium iodide-positive endothelial cells). An amino acid (glycine, alanine, aspartate)-containing base Solution with N-acetylhistidine as buffer was optimized. The optimized base Solution with pH 7.0 and potassium and chloride as main ions yielded a further decrease of endothelial cell injury. Combination of deferoxamine (in lower concentration, ie, 0.1 mmol/L) with the new, more membrane-permeable iron chelator LK 614 (20 μmol/L) further improved Preservation so that even after 3 weeks of cold storage plus 3 hours rewarming only 10 ± 1% of endothelial cells were propidium iodide positive. In this optimized Solution, both endothelial cell survival and mitochondrial membrane potential were significantly better preserved than in the clinically used Solutions HTK, University of Wisconsin (UW) and Perfadex, or in physiological saline. Thrombocyte adhesion was also significantly reduced after cold storage in the optimized Solution compared with HTK Solution. Conclusion Cold-induced injury to the endothelium of porcine aortic segments is, as the injury to cultured endothelial cells, mediated by chelatable iron. Thus, iron chelators, but also optimized base Solutions, are options to improve the storage of vascular endothelium. The optimized Solution should now be tested in in vivo animal experiments.
Gerhard Rakhorst - One of the best experts on this subject based on the ideXlab platform.
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Effect of University of Wisconsin organ-Preservation Solution on haemorheology
Transplant International, 2004Co-Authors: Arjan Plaats, Rutger J. Ploeg, Nils A. Hart, Aurora M. Morariu, Gijsbertus J. Verkerke, Henri G. D. Leuvenink, Gerhard RakhorstAbstract:In conventional cold-storage organ Preservation, the donor organ is flushed with University of Wisconsin (UW) Solution at 0–4°C. The initial flush is used to wash out blood from the microcirculation to allow optimal Preservation with the UW Solution. The component hydroxyethyl starch (HES) of UW is known to cause relatively high viscosity and a possible interaction with blood, i.e. increased red blood cell (RBC) aggregation. The aim of this study was to investigate the influence of the HES component on the viscosity of UW and the aggregation behaviour of blood during washout. Viscosity aspects were measured with a cone-plate rheometer. HES-induced RBC aggregation was studied by means of an optical aggregation measuring device. The experiments were carried out with rat whole blood and mixtures of rat whole blood with UW-Solution and UW without HES (UWmod), at 4°C. The viscosity of blood at 4°C is two-times higher than at 37°C; the UW/blood mixture at 4°C is 1.3-times more viscous than blood at 37°C; the 4°C UWmod/blood mixture equals the viscosity of blood at 37°C. The UW/blood mixture shows a ninefold increased aggregation compared with whole blood. These aggregates are larger than the diameter of the sinusoids in the rat liver. A mixture of whole blood and UWmod shows a lower aggregation than blood. Apart from an increased viscosity, HES in UW causes increased RBC aggregation. The aggregates are larger than the diameter of the sinusoids. Initial washout could be optimised by pre-flushing to improve the viability of the liver and to decrease delayed graft function.