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Peter Schemmer - One of the best experts on this subject based on the ideXlab platform.
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HTK-N, a modified HTK Solution, decreases preservation injury in a model of microsteatotic rat liver transplantation
Langenbeck's Archives of Surgery, 2012Co-Authors: Helge Bruns, Ursula Rauen, Daniel Schultze, Markus Zorn, Christa Flechtenmacher, Beate K. Straub, Peter SchemmerAbstract:Background Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) Solution, HTK-N, has been developed. This Solution contains N -acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury. Methods Microvesicular steatosis was induced by a single dose of ethanol (8 g/kg BW). Livers were harvested and stored at 4 °C for 8 h with HTK or HTK-N before transplantation. Tissue and blood samples were taken at 1, 8, and 24 h after reperfusion to compare serum liver enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), standard histology, and immunohistochemistry for myeloperoxidase (MPO), caspase-3, and inducible nitric oxide synthase. Survival was compared after 1 week. For statistics, Analysis of Variance and t test were used. Results HTK-N improved survival from 12.5 % in HTK to 87.5 % ( p
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HTK-N, a modified HTK Solution, decreases preservation injury in a model of microsteatotic rat liver transplantation.
Langenbeck's Archives of Surgery, 2012Co-Authors: Qinlong Liu, Helge Bruns, Ursula Rauen, Daniel Schultze, Yi Xue, Markus Zorn, Christa Flechtenmacher, Beate K. Straub, Peter SchemmerAbstract:Background Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) Solution, HTK-N, has been developed. This Solution contains N-acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury.
Ursula Rauen - One of the best experts on this subject based on the ideXlab platform.
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Cold Storage Injury to Rat Small-bowel Transplants-Beneficial Effect of a Modified HTK Solution.
Transplantation, 2018Co-Authors: Ingmar Lautenschläger, Ursula Rauen, Herbert De Groot, Gesine Pless-petig, Peter Middel, Tomislav StojanovicAbstract:BACKGROUND The small bowel is prone to ischemic injury during transport before transplantation, an injury that endangers the recipient patient. The small-bowel mucosal microcirculation in particular appears to be highly sensitive to injury. Current preservation Solutions such as histidine-tryptophan-ketoglutarate (HTK) Solution provide some protection to the graft. However, these were developed decades ago and do not address several critical processes, such as hypoxia-induced membrane pores and free radical-mediated hypothermic injury. METHODS To protect the graft from cold ischemic injury, we implemented a modified HTK Solution here, including glycine, alanine, and iron chelators in a heterotopic, syngeneic small-bowel transplantation model of the rat. The effects of the modified Solution and its major components were compared against the conventional HTK Solution using intravital microscopy in the early reperfusion period. RESULTS The amino acid glycine, added to HTK Solution, slightly improved mucosal perfusion. Both, the modified base Solution (without iron chelators) and iron chelators increased functional capillary density of the mucosa during the early reperfusion period. The complete modified Solution (with glycine, alanine, and iron chelators) significantly increased the perfusion index, functional capillary density of the mucosa, and red blood cell velocity in the grafts after reperfusion in comparison with the grafts preserved with HTK. CONCLUSIONS The modified preservation Solution improved the microcirculation of the transplants and needs detailed evaluation in further models of small-bowel transplantation.
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HTK-N, a modified HTK Solution, decreases preservation injury in a model of microsteatotic rat liver transplantation
Langenbeck's Archives of Surgery, 2012Co-Authors: Helge Bruns, Ursula Rauen, Daniel Schultze, Markus Zorn, Christa Flechtenmacher, Beate K. Straub, Peter SchemmerAbstract:Background Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) Solution, HTK-N, has been developed. This Solution contains N -acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury. Methods Microvesicular steatosis was induced by a single dose of ethanol (8 g/kg BW). Livers were harvested and stored at 4 °C for 8 h with HTK or HTK-N before transplantation. Tissue and blood samples were taken at 1, 8, and 24 h after reperfusion to compare serum liver enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), standard histology, and immunohistochemistry for myeloperoxidase (MPO), caspase-3, and inducible nitric oxide synthase. Survival was compared after 1 week. For statistics, Analysis of Variance and t test were used. Results HTK-N improved survival from 12.5 % in HTK to 87.5 % ( p
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HTK-N, a modified HTK Solution, decreases preservation injury in a model of microsteatotic rat liver transplantation.
Langenbeck's Archives of Surgery, 2012Co-Authors: Qinlong Liu, Helge Bruns, Ursula Rauen, Daniel Schultze, Yi Xue, Markus Zorn, Christa Flechtenmacher, Beate K. Straub, Peter SchemmerAbstract:Background Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) Solution, HTK-N, has been developed. This Solution contains N-acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury.
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Use of a new modified HTK Solution for machine preservation of marginal liver grafts.
Journal of Surgical Research, 2010Co-Authors: Judith Stegemann, Ursula Rauen, Andreas Hirner, Thomas MinorAbstract:Background The present study was undertaken to investigate the putative benefit of a new, modified HTK Solution for hypothermic machine perfusion using a model of rat livers from non-heart beating donors. Methods Livers were retrieved 30 min after cardiac arrest of male Wistar rats and put on a recirculating machine perfusion device. Hypothermic machine perfusion (HMP) was performed for 18 h at 4°C and a rate of 0.5 mL/g−1 min−1 while the preservation Solution was oxygenated with 100% O2. Each liver was randomly assigned to the use of one of the following preservation Solutions: HTK (histidine-tryptophan-ketoglutarate Solution); Custodiol-N base Solution (modified HTK-Solution) without additives or with the addition of 25 μM deferoxamine + 2.5 μM (Custodiol-N, 2.5) or 7.5 μM (Custodiol-N) of the permeable iron chelator LK 614. Viability of livers was evaluated upon reperfusion in vitro with Krebs-Henseleit buffer according to previously validated techniques for 120 min at 37°C. Results The use of Custodiol-N base Solution led to a significantly decreased release of ALT or LDH during HMP and after reperfusion, which was further reduced by Custodiol-N and minimal use of Custodiol-N, 2.5. Only the use of Custodiol-N, 2.5 resulted in an improvement of metabolic activity upon reperfusion, as evaluated by hepatic production of C02, significantly reduced cleavage of caspase 9, and abrogated positive signs of cellular of apoptosis [terminal deoxynucleotide transferase-mediated deoxy-UTP nick-end labeling (TUNEL)-test)]. Conclusion The data presented provide first experimental evidence for enhanced organ protective potential of the new Custodiol-N Solution compared with HTK upon hypothemic machine preservation of marginal liver grafts. Moreover, for continuous perfusion preservation the dosage of the lipophilic chelator LK 614 should probably be lower than for static cold storage.
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Evaluation of a Modified HTK Solution Containing the New Iron Chelator LK 614 in an Isolated Rat Liver Perfusion Model
Journal of Investigative Surgery, 2009Co-Authors: Jeremias Wohlschlaeger, Herbert De Groot, Ursula RauenAbstract:Background: Cold storage-induced injury to donor organs remains a persistent problem in transplantation medicine. We here evaluated a modified HTK Solution including, among others, a new, membrane-permeable iron chelator, LK 614, in the isolated perfused rat liver model. Methods: Rat livers were stored at 4°C for 24 hr in modified HTK Solution, in modified HTK Solution with LK 614 or in traditional HTK Solution, and reperfused for 60 min at 37°C with Krebs-Henseleit buffer (KH buffer). Bile secretion and lactate dehydrogenase (LDH) release into the perfusate were measured, and hepatic microcirculation evaluated optically after the addition of trypan blue to the perfusate. Biopsies were evaluated by a pathologist blinded to the experimental conditions. Results: Compared with HTK-preserved livers, LDH leakage was significantly lower and bile secretion significantly higher in the modified HTK Solution with the iron chelator (both p
Helge Bruns - One of the best experts on this subject based on the ideXlab platform.
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HTK-N, a modified HTK Solution, decreases preservation injury in a model of microsteatotic rat liver transplantation
Langenbeck's Archives of Surgery, 2012Co-Authors: Helge Bruns, Ursula Rauen, Daniel Schultze, Markus Zorn, Christa Flechtenmacher, Beate K. Straub, Peter SchemmerAbstract:Background Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) Solution, HTK-N, has been developed. This Solution contains N -acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury. Methods Microvesicular steatosis was induced by a single dose of ethanol (8 g/kg BW). Livers were harvested and stored at 4 °C for 8 h with HTK or HTK-N before transplantation. Tissue and blood samples were taken at 1, 8, and 24 h after reperfusion to compare serum liver enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), standard histology, and immunohistochemistry for myeloperoxidase (MPO), caspase-3, and inducible nitric oxide synthase. Survival was compared after 1 week. For statistics, Analysis of Variance and t test were used. Results HTK-N improved survival from 12.5 % in HTK to 87.5 % ( p
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HTK-N, a modified HTK Solution, decreases preservation injury in a model of microsteatotic rat liver transplantation.
Langenbeck's Archives of Surgery, 2012Co-Authors: Qinlong Liu, Helge Bruns, Ursula Rauen, Daniel Schultze, Yi Xue, Markus Zorn, Christa Flechtenmacher, Beate K. Straub, Peter SchemmerAbstract:Background Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) Solution, HTK-N, has been developed. This Solution contains N-acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury.
H J Bretschneider - One of the best experts on this subject based on the ideXlab platform.
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comparison of histidine tryptophan ketoglutarate HTK Solution versus university of wisconsin uw Solution for organ preservation in human liver transplantation a prospective randomized study
Transplant International, 1994Co-Authors: J Erhard, H J Bretschneider, R Lange, R Scherer, Wolfgang J Kox, M M Gebhard, F W EiglerAbstract:Over a 30-month period, 60 patients (30 in each group) suffering from end-stage liver disease or primary hepatic malignancy and scheduled for liver transplantation were enrolled in a prospective, randomized study to compare two methods of liver preservation: histidinetryptophan-ketoglutarate (HTK) Solution versus University of Wisconsin (UW) Solution. Entry criteria for both groups were: age (18–65 years), elective surgery (transplantable or urgent category of the recipients), first transplantations and harvesting procedure performed by the same team. The parameters under investigation were the clinical and laboratory data preand post-transplantation, as well as follow-up data such as complications and survival. There were no significant differences in the two groups as far as the evaluation criteria were concerned, even when cold ischemia time was more than 15h (n=7). A slight, yet not significant, increase in late complications of the biliary anastomoses could be seen in the UW group. Hepatocellular injury (SGOT, SGPT, GLDH, lactate) appeared to be more marked in the HTK group. These results suggest that both HTK and UW Solutions are appropriate for clinical use in liver transplantation, even if cold ischemia time is more than 15h.
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HTK-Solution (Bretschneider) for human liver transplantation
Langenbecks Archiv für Chirurgie, 1990Co-Authors: G Gubernatis, R Pichlmayr, P Lamesch, H Grosse, A Bornscheuer, H J Meyer, B Ringe, M Farle, H J BretschneiderAbstract:Die kardioplegische Lösung HTK nach Bretschneider ist bisher noch nicht im Bereich der klinischen Lebertransplantation verwendet worden. Hier werden die ersten Ergebnisse von 14 Patienten vorgestellt, denen eine mit HTK-Lösung protektionierte Leber transplantiert wurde. Die Eignung der HTK-Lösung konnte gezeigt werden. Alle Transplantate zeigten eine Primärfunktion mit Ausnahme eines Transplantates, bei dem die initiale Nichtfunktion zweifelsfrei spenderbedingt war. Die höchsten friihpostoperativen Werte der Transaminasen, die als Zeichen des Ischämieschadens herangezogen wurden, waren durchschnittlich und vergleichbar mit den Transaminasenausschüttungen nach anderen Lösungen. Unter Verwendung der HTK-Lösung konnte eine Primarfunktion selbst bei solchen Transplantaten erzielt werden, die prospektiv als solche von problematischer oder geringer Qualität eingeschätzt worden waren, and Lebern mit schlechten Funktionstesten (MegX) funktionierten von Beginn an. Deshalb scheint die HTK-L6sung die Ausweitung der Akzeptanzkriterien für Spenderlebern zu ermöglichen. Es war nicht das Ziel dieser Studie, die kalte Ischämiezeit zu verlängern, aber drei Transplantate mit 11 h and 12 h 25 min nahmen unmittelbar nach Reperfusion ihre Funktion auf. Wie weft die kalte Ischämiezeit ausgedehnt werden kann, ist noch eine offene Frage. Alle Spenderlebern wurden aufgrund der geringen Viskosität der HTK-Lösung schlagartig gekühlt und homogen perfundiert. Alle Lebern hatten eine weiche Konsistenz nach der Perfusion, was kein oder nur ein geringes Zellödem bedeutet. Aus diesen Gründen ist HTK eine effektive Lösung für die Leberkonservierung. The cardioplegic HTK-Solution (Bretschneider) has not been used in human liver transplantation as yet. Herein the first results obtained from 14 patients with HTK-preserved liver grafts are presented. The suitability of HTK-Solution could be shown. All grafts functioned primarily except one, where initial non-function was obviously due to donor reasons. The early postoperative peak values of transaminases as a sign of ischemic damage were average and similar to the values of other flushout Solutions. Using HTK primary function could be achieved even in livers prospectively assessed as only of fair quality, and livers with poor donor function tests (MegX) functioned from the beginning. HTK-Solution therefore seems to allow widening of the acceptance criteria for donor livers. It was not the aim of this trial to extend cold ischemic time, but 3 livers with 11 h and 12 h 25 showed immediate function. How far cold ischemic time can be extended is a still open question. All livers were rapidly cooled and homogeneously flushed out due to the low viscosity of HTK-Solution. All livers had a soft consistency after perfusion indicating a low degree of cell edema. HTK therefore is an effective Solution for liver preservation.
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HTK Solution bretschneider for human liver transplantation first clinical experiences
Langenbeck's Archives of Surgery, 1990Co-Authors: G Gubernatis, R Pichlmayr, P Lamesch, H Grosse, A Bornscheuer, H J Meyer, B Ringe, M Farle, H J BretschneiderAbstract:The cardioplegic HTK-Solution (Bretschneider) has not been used in human liver transplantation as yet. Herein the first results obtained from 14 patients with HTK-preserved liver grafts are presented. The suitability of HTK-Solution could be shown. All grafts functioned primarily except one, where initial non-function was obviously due to donor reasons. The early postoperative peak values of transaminases as a sign of ischemic damage were average and similar to the values of other flushout Solutions. Using HTK primary function could be achieved even in livers prospectively assessed as only of fair quality, and livers with poor donor function tests (MegX) functioned from the beginning. HTK-Solution therefore seems to allow widening of the acceptance criteria for donor livers. It was not the aim of this trial to extend cold ischemic time, but 3 livers with 11 h and 12 h 25 showed immediate function. How far cold ischemic time can be extended is a still open question. All livers were rapidly cooled and homogeneously flushed out due to the low viscosity of HTK-Solution. All livers had a soft consistency after perfusion indicating a low degree of cell edema. HTK therefore is an effective Solution for liver preservation.
Christa Flechtenmacher - One of the best experts on this subject based on the ideXlab platform.
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HTK-N, a modified HTK Solution, decreases preservation injury in a model of microsteatotic rat liver transplantation
Langenbeck's Archives of Surgery, 2012Co-Authors: Helge Bruns, Ursula Rauen, Daniel Schultze, Markus Zorn, Christa Flechtenmacher, Beate K. Straub, Peter SchemmerAbstract:Background Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) Solution, HTK-N, has been developed. This Solution contains N -acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury. Methods Microvesicular steatosis was induced by a single dose of ethanol (8 g/kg BW). Livers were harvested and stored at 4 °C for 8 h with HTK or HTK-N before transplantation. Tissue and blood samples were taken at 1, 8, and 24 h after reperfusion to compare serum liver enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), standard histology, and immunohistochemistry for myeloperoxidase (MPO), caspase-3, and inducible nitric oxide synthase. Survival was compared after 1 week. For statistics, Analysis of Variance and t test were used. Results HTK-N improved survival from 12.5 % in HTK to 87.5 % ( p
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HTK-N, a modified HTK Solution, decreases preservation injury in a model of microsteatotic rat liver transplantation.
Langenbeck's Archives of Surgery, 2012Co-Authors: Qinlong Liu, Helge Bruns, Ursula Rauen, Daniel Schultze, Yi Xue, Markus Zorn, Christa Flechtenmacher, Beate K. Straub, Peter SchemmerAbstract:Background Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) Solution, HTK-N, has been developed. This Solution contains N-acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury.