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Jonathan A. Fridell - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of Histidine‐Tryptophan‐Ketoglutarate and University of Wisconsin preservation solutions in pediatric liver transplantation
    Pediatric Transplantation, 2018
    Co-Authors: Richard S. Mangus, Joel R. Schroering, Taylor J. Hathaway, Chandrashekhar A. Kubal, Jonathan A. Fridell
    Abstract:

    UW and HTK solutions are the two primary organ preservation solutions most used in the United States. This study analyzes use of the two solutions in all pediatric liver transplants performed at a single center between 2001and 2017. Outcome measures included early graft function, as well as graft and patient survival. Bile duct complications were reviewed. Operative technique, immunosuppressive protocols, and donor acceptance criteria remained uniform among participating surgeons throughout the study period. There were 104 pediatric liver transplants with complete data during the study period, 75 preserved with HTK (68%) and 29 with UW (26%). Demographics were similar. Cold and warm ischemia times were similar. Peak ALT post-transplant was higher in the UW group at both peak and post-transplant day 3. The peak TB levels were similar. Bile duct strictures were more common in the UW group (44% vs 16%, P < .01). Early graft survival was statistically similar at 7-, 90- and 365-days post-transplant. Cox regression graft survival was similar at 10-years. This study suggests that use of HTK in pediatric liver transplantation is safe with outcomes similar to UW, though bile duct stricture rates may be lower with HTK.

  • Histidine-Tryptophan-Ketoglutarate for pancreas allograft preservation: the Indiana University experience.
    American Journal of Transplantation, 2010
    Co-Authors: Jonathan A. Fridell, Richard S. Mangus, John A. Powelson
    Abstract:

    Histidine-Tryptophan-Ketoglutarate solution (HTK) has been scrutinized for use in pancreas transplantation. A recent case series and a United Network for Organ Sharing data base review have suggested an increased incidence of allograft pancreatitis and graft loss with HTK compared to the University of Wisconsin solution (UW). Conversely, a recent randomized, controlled study failed to show any significant difference between HTK and UW for pancreas allograft preservation. This study was a retrospective review of all pancreas transplants performed at Indiana University between 2003 and 2009 comparing preservation with HTK or UW. Data included recipient and donor demographics, 7-day, 90-day and 1-year graft survival, peak 30-day serum amylase and lipase, HbA1c and C-peptide levels. Of the 308 pancreas transplants, 84% used HTK and 16% UW. There were more SPK compared to pancreas after kidney and pancreas transplant alone in the HTK group. Donor and recipient demographics were similar. There was no significant difference in 7-day, 90-day or 1-year graft survival, 30-day peak serum amylase and lipase, HbA1c or C-peptide. No clinically significant difference between HTK and UW for pancreas allograft preservation was identified. Specifically, in the context of low-to-moderate flush volume and short cold ischemia time (≤10 h), no increased incidence of allograft pancreatitis or graft loss was observed.

  • clinical experience with histidine tryptophan ketoglutarate solution in abdominal organ preservation a review of recent literature
    Clinical Transplantation, 2009
    Co-Authors: Jonathan A. Fridell, Richard S. Mangus, A J Tector
    Abstract:

    Histidine-Tryptophan-Ketoglutarate (HTK) solution was introduced by Bretschneider as a cardioplegia solution in the early 1980s and has subsequently been applied to organ preservation for transplantation in Europe during the 1980s and in North America during the last six yr. With the increasing use of HTK for primary preservation, it is important that the transplant community be aware of the properties of this solution and the advantages and disadvantages of its use. Even if a center uses an alternative preservation solution, it is likely that import offers will be made for allografts that have been preserved in HTK. In this review article, recent literature describing the clinical use of HTK in abdominal transplantation will be summarized with references to earlier reports when indicated.

  • comparison of histidine tryptophan ketoglutarate solution and university of wisconsin solution in intestinal and multivisceral transplantation
    Transplantation, 2008
    Co-Authors: Richard S. Mangus, Jonathan A. Fridell, Joe A Tector, Marwan Kazimi, Edward F Hollinger, Rodrigo Vianna
    Abstract:

    Background. Previous studies have failed to demonstrate a clinical difference between histidine-tryptophanketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in clinical transplant outcomes for liver, pancreas, and kidney transplantation. This study compares HTK and UW in bowel transplantation with primary outcomes being graft and patient survival, early graft function, and episodes of rejection. Methods. Data were extracted using a retrospective chart and medical record review of all bowel transplants between 2003 and 2007, and included both pediatric and adult grafts. Transplanted organs included isolated small bowel, modified multivisceral (bowel, pancreas, and stomach) and multivisceral (bowel, pancreas, stomach, and liver). Immunosuppression included induction with a steroid taper and antithymocyte globulin and anti-CD20 monoclonal antibody (rituximab), followed by maintenance with prograf monotherapy. Bowel surveillance was performed with twice weekly zoom endoscopy and biopsy. Results. There were 54 patients transplanted with 57 grafts, 22 preserved in UW, and 37 in HTK. No differences were noted between the two solutions in initial graft function, appearance of bowel on initial endoscopy, and number of rejection episodes. There were no episodes of pancreatitis in the 44 multivisceral grafts which included a transplant pancreas (14 UW and 30 HTK). Kaplan-Meier survival analysis did not demonstrate a significant difference in graft or patient survival at 30- or 90-days posttransplant. Conclusions.IntestinalgraftspreservedinUWandHTKdemonstratenodifferenceingraftandpatientsurvivalat30and 90-days posttransplant. There were no differences noted in initial function, endoscopic appearance, rejection episodes, or transplant pancreatitis.

  • comparison of histidine tryptophan ketoglutarate solution and university of wisconsin solution in prolonged cold preservation of kidney allografts
    Transplantation, 2006
    Co-Authors: Avinash Agarwal, P. Murdock, Jonathan A. Fridell
    Abstract:

    Although University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation, Histidine-Tryptophan Ketogluatarate (HTK) solution has been increasingly used. This study compared HTK or UW for cold static storage of kidney allografts. In all, 149 renal transplants were performed with cold ischemic times (CI) greater than 16 hr (UW 87, HTK 62) and a subset analysis was performed with CI over 24 hr (HTK 31, UW 38). Data from receiving renal transplant centers focused on delayed graft function (DGF), patient and allograft survival. In CI greater than 16 hr, graft and patient survival were comparable. HTK cohort had lower DGF. In CI greater than 24 hr, there was no difference in patient survival, a trend towards improved graft survival in HTK, and decreased rate of DGF in HTK. This data suggests that UW and HTK have at least similar efficacy in kidney preservation at longer ischemic times.

Frank Dombrowski - One of the best experts on this subject based on the ideXlab platform.

  • Kidney transplantation from non-heart-beating donors after oxygenated low-flow machine perfusion preservation with histidine–tryptophan–ketoglutarate solution
    Transplant International, 2005
    Co-Authors: Thomas Minor, Mario Sitzia, Frank Dombrowski
    Abstract:

    The aim of this study was to determine the potential benefit of aerobic machine preservation (MP) with non-colloidal histidine–tryptophan–ketoglutarate (HTK) solution compared with MP with Belzer machine perfusion solution (MPS) and standard cold storage, after marginal kidneys had been obtained from non-heart-beating donors. Cardiac arrest was electrically induced in anaesthetized German landrace pigs (20–25 kg bw). Their kidneys were harvested 40 min thereafter, flushed with HTK by gravity of 100 cm H_2O via the renal artery and then stored in HTK for 18 h at 4°C. Other organs were subjected to oxygenated (pO_2>500 mmHg) hypothermic pulsatile low-flow machine perfusion with HTK or MP with Belzer MPS at P_max=40 mmHg, yielding transrenal flow values of 0.2–0.3 ml/min per g with HTK and approximately twice that amount with Belzer MPS. A well-preserved vascular endothelium and intact tubular epithelium were documented by electron microscopy at the end of perfusion preservation in both solutions as well as after cold storage. Concentrations of ATP (in micromoles per gramme) in tissue homogenates at the end of perfusion preservation with HTK were 1.18±0.12 vs 0.16±0.02 ( P

  • kidney transplantation from non heart beating donors after oxygenated low flow machine perfusion preservation with histidine tryptophan ketoglutarate solution
    Transplant International, 2004
    Co-Authors: Thomas Minor, Mario Sitzia, Frank Dombrowski
    Abstract:

    The aim of this study was to determine the potential benefit of aerobic machine preservation (MP) with non-colloidal Histidine-Tryptophan-Ketoglutarate (HTK) solution compared with MP with Belzer machine perfusion solution (MPS) and standard cold storage, after marginal kidneys had been obtained from non-heart-beating donors. Cardiac arrest was electrically induced in anaesthetized German landrace pigs (20-25 kg bw). Their kidneys were harvested 40 min thereafter, flushed with HTK by gravity of 100 cm H2O via the renal artery and then stored in HTK for 18 h at 4 degrees C. Other organs were subjected to oxygenated (pO2>500 mmHg) hypothermic pulsatile low-flow machine perfusion with HTK or MP with Belzer MPS at P(max)=40 mmHg, yielding transrenal flow values of 0.2-0.3 ml/min per g with HTK and approximately twice that amount with Belzer MPS. A well-preserved vascular endothelium and intact tubular epithelium were documented by electron microscopy at the end of perfusion preservation in both solutions as well as after cold storage. Concentrations of ATP (in micromoles per gramme) in tissue homogenates at the end of perfusion preservation with HTK were 1.18+/-0.12 vs 0.16+/-0.02 (P<0.05) after simple cold storage and 2.43+/-0.23 after perfusion with Belzer MPS, thus documenting a relevant effect of low-flow perfusion on tissue oxygenation. Viability of the grafts was followed for 1 week after heterotopic transplantation and bilateral nephrectomy in the recipient pigs. Machine perfusion with HTK significantly improved cortical microcirculation upon early reperfusion in vivo, as well as maximal serum levels of urea and creatinine, compared to recipients receiving cold-stored grafts. No differences could be found between MP with HTK or Belzer MPS. In conclusion, provision of oxygen during storage is possible by low-flow perfusion with HTK as with Belzer MPS and apparently improves graft viability after transplantation.

  • Kidney transplantation from non-heart-beating donors after oxygenated low-flow machine perfusion preservation with Histidine-Tryptophan-Ketoglutarate solution.
    Transplant International, 2004
    Co-Authors: Thomas Minor, Mario Sitzia, Frank Dombrowski
    Abstract:

    The aim of this study was to determine the potential benefit of aerobic machine preservation (MP) with non-colloidal Histidine-Tryptophan-Ketoglutarate (HTK) solution compared with MP with Belzer machine perfusion solution (MPS) and standard cold storage, after marginal kidneys had been obtained from non-heart-beating donors. Cardiac arrest was electrically induced in anaesthetized German landrace pigs (20-25 kg bw). Their kidneys were harvested 40 min thereafter, flushed with HTK by gravity of 100 cm H2O via the renal artery and then stored in HTK for 18 h at 4 degrees C. Other organs were subjected to oxygenated (pO2>500 mmHg) hypothermic pulsatile low-flow machine perfusion with HTK or MP with Belzer MPS at P(max)=40 mmHg, yielding transrenal flow values of 0.2-0.3 ml/min per g with HTK and approximately twice that amount with Belzer MPS. A well-preserved vascular endothelium and intact tubular epithelium were documented by electron microscopy at the end of perfusion preservation in both solutions as well as after cold storage. Concentrations of ATP (in micromoles per gramme) in tissue homogenates at the end of perfusion preservation with HTK were 1.18+/-0.12 vs 0.16+/-0.02 (P

Christoph E. Broelsch - One of the best experts on this subject based on the ideXlab platform.

  • Histidine-Tryptophan-Ketoglutarate versus University of Wisconsin solution in living donor liver transplantation: Results of a prospective study
    Liver Transplantation, 2003
    Co-Authors: Giuliano Testa, Massimo Malagó, Silvio Nadalin, Boris Treptow, Andreas Paul, Andrea Frilling, Christoph E. Broelsch
    Abstract:

    The grafts obtained from a living donor hepatectomy are perfused on the back table with either University of Wisconsin solution (UW) or Histidine-Tryptophan-Ketoglutarate solution (HTK). The efficacy and safety of these solutions have been studied in cadaveric liver transplantation, however, there is no study comparing the two solutions in adult-to-adult living donor liver transplantation. In this study, UW and HTK were used in the perfusion of right living donor grafts. The grafts were perfused with a predetermined sequence and volume of one of the solutions. Liver biochemistries, complications, and graft and patient survival were analyzed. From January 2001 to September 2002, 30 grafts were alternately perfused with either UW (UW group) or HTK (HTK group). The perfusion was performed first via the artery and then via the portal vein with a predetermined volume. At a mean follow-up of 13 +/- 7 months, no significant statistical difference between groups UW and HTK in posttransplantation liver biochemistries, complications, or patient and graft survival (84% and 80%, respectively) was observed. In conclusion, UW and HTK are equally effective and safe in the perfusion of the living donor liver grafts. HTK has a slight practical advantage over UW because it does not need to be flushed away before reperfusion of the graft and is less expensive.

  • Celsior solution compared with University of Wisconsin solution (UW) and histidine–tryptophan–ketoglutarate solution (HTK) in the protection of human hepatocytes against ischemia–reperfusion injury
    Transplant International, 2003
    Co-Authors: Hermann Janßen, Petra H. E. Janßen, Christoph E. Broelsch
    Abstract:

    Celsior, a new preservation solution in thoracic organ transplantation was evaluated for efficacy in cold preservation of human hepatocytes and compared with University of Wisconsin solution (UW) and histidine–tryptophan–ketoglutarate solution (HTK, Custodiol). Human hepatocyte cultures were preserved at 4 °C in Celsior, UW and HTK for 2, 6, 12, 24 and 48 h with 6 h of reperfusion. Levels of lactate dehydrogenase (LDH; cell necrosis), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT; mitochondrial function), and adenosine 5′-triphosphate (ATP; loss of intracellular energy) were measured. Cell necrosis, mitochondrial dysfunction, and loss of ATP were significantly ( P

Ursula Rauen - One of the best experts on this subject based on the ideXlab platform.

  • HTK-N, a modified HTK solution, decreases preservation injury in a model of microsteatotic rat liver transplantation
    Langenbeck's Archives of Surgery, 2012
    Co-Authors: Helge Bruns, Ursula Rauen, Daniel Schultze, Markus Zorn, Christa Flechtenmacher, Beate K. Straub, Peter Schemmer
    Abstract:

    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  

  • HTK-N, a modified HTK solution, decreases preservation injury in a model of microsteatotic rat liver transplantation.
    Langenbeck's Archives of Surgery, 2012
    Co-Authors: Qinlong Liu, Helge Bruns, Ursula Rauen, Daniel Schultze, Yi Xue, Markus Zorn, Christa Flechtenmacher, Beate K. Straub, Peter Schemmer
    Abstract:

    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.

  • prolonged cold storage using a new histidine tryptophan ketoglutarate based preservation solution in isogeneic cardiac mouse grafts
    European Heart Journal, 2011
    Co-Authors: Tobias R Turk, Ingrid Wiswedel, Herbert De Groot, Ursula Rauen, Thorsten Feldkamp, Hideo A Baba, Andreas Kribben, Oliver Witzke
    Abstract:

    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.

  • Inherent toxicity of organ preservation solutions to cultured hepatocytes.
    Cryobiology, 2007
    Co-Authors: Ursula Rauen, Herbert De Groot
    Abstract:

    Abstract Organ preservation solutions have been designed to protect grafts against the injury inflicted by cold ischemia. However, toxicity of University of Wisconsin (UW) solution during rewarming has been reported. Therefore, we here assessed the toxicity of UW, histidine–tryptophan–ketoglutarate (HTK), Euro-Collins, histidine–lactobionate (HL), sodium–lactobionate–sucrose and Celsior solutions in cultured hepatocytes under hypothermic (4 °C), intermediate (21 °C) and physiological (37 °C) conditions. Marked toxicity of UW, HTK, HL and Euro-Collins solutions was observed at both 37 and 21 °C. With the exception of UW solution, these solutions also increased cell injury during cold incubation (LDH release after 18 h at 4 °C: HTK 76 ± 2%, Euro-Collins 78 ± 17%, HL 81 ± 15%; control: Krebs–Henseleit buffer 20 ± 6%). Testing of individual components using modified Krebs–Henseleit buffers suggested that histidine and phosphate are responsible for (part of) this toxicity. These potential toxicities should be taken into account in the development of future preservation solutions.

  • Preservation of pig liver allografts after warm ischemia: normothermic perfusion versus cold storage
    Langenbecks Archiv für Chirurgie, 1997
    Co-Authors: A. Hellinger, Ursula Rauen, R. Lange, J. Erhard, F. W. Eigler, R. Fiegen, H. Groot, U. Schmidt, H. Hirche, S. Kaiser
    Abstract:

    Warm ischemia is known to induce substantial damage to the liver parenchyma. With respect to clinical liver transplantation, the tolerance of the liver to warm ischemia and the preservation of these organs have not been studied in detail. In isolated reperfused pig livers we proceeded according to the following concept: Livers were subjected to 1 or 3 h of warm ischemia. Subsequently, these organs were preserved by either normothermic perfusion or cold storage (histidine-tryptophan-α-ketoglutarate, HTK) for 3 h each. After storage, liver function was assessed in a reperfusion circuit for another 3 h. Parameters under evaluation were bile flow, perfusion flow, oxygen consumption, enzyme release into the perfusate (creatine kinase, glutamic oxaloacetic transaminase (GOT), lactic dehydrogenase, and glutamic pyruvic transaminase), and histomorphology. Damage to the liver was lowest after warm ischemia of 1 h. The results after cold storage were superior to those after normothermic perfusion (GOT: 3.2±0.3 and 2.6±0.2 U/g liver; cumulative bile production: 14.7±2.1 and 9.4±1 ml, respectively; P

R Steininger - One of the best experts on this subject based on the ideXlab platform.

  • histidine tryptophan ketoglutarate solution for organ preservation in human liver transplantation a prospective multi centre observation study
    Transplant International, 2004
    Co-Authors: Herwig Pokorny, Susanne Rasoulrockenschaub, Felix B Langer, Thomas Windhager, Andreas Rosenstingl, R Lange, Alfred Konigsrainer, Burckhardt Ringe, F Muhlbacher, R Steininger
    Abstract:

    Based on experimental work and clinical small studies, Histidine-Tryptophan-Ketoglutarate (HTK) solution was found to be suitable not only for heart and kidney preservation but also for liver preservation. We decided, therefore, to use this preservation solution for clinical liver preservation in a prospective multi-centre trial. Enrolment to the study was from 1996 to 1999 in four European centres, and the results of 214 patients with HTK-preserved organs were analysed. Analysis showed a primary dysfunction (PDF) rate of 8.8%, with a primary non-function (PNF) rate of 2.3% and initial poor function (IPF) in 6.5%. Patient survival rate at 1 year was 83% and 1-year graft survival rate was 80%. In a univariate and a multivariate analysis PDF, early surgical complications and tendentiously severe infections (septicaemia, pneumonia, cholangitis) were identified as independent risk factors for graft and patient survival. Preservation with HTK can be regarded as an established alternative to preservation with University of Wisconsin (UW) solution when preservation times are short. Definitive assessment of the efficacy of preservation solutions requires further prospective randomised clinical trials that compare HTK and UW.

  • Histidine–tryptophan–ketoglutarate solution for organ preservation in human liver transplantation—a prospective multi-centre observation study
    Transplant International, 2004
    Co-Authors: Herwig Pokorny, Thomas Windhager, Andreas Rosenstingl, R Lange, Alfred Konigsrainer, Burckhardt Ringe, F Muhlbacher, Susanne Rasoul-rockenschaub, Felix Langer, R Steininger
    Abstract:

    Based on experimental work and clinical small studies, histidine–tryptophan–ketoglutarate (HTK) solution was found to be suitable not only for heart and kidney preservation but also for liver preservation. We decided, therefore, to use this preservation solution for clinical liver preservation in a prospective multi-centre trial. Enrolment to the study was from 1996 to 1999 in four European centres, and the results of 214 patients with HTK-preserved organs were analysed. Analysis showed a primary dysfunction (PDF) rate of 8.8%, with a primary non-function (PNF) rate of 2.3% and initial poor function (IPF) in 6.5%. Patient survival rate at 1 year was 83% and 1-year graft survival rate was 80%. In a univariate and a multivariate analysis PDF, early surgical complications and tendentiously severe infections (septicaemia, pneumonia, cholangitis) were identified as independent risk factors for graft and patient survival. Preservation with HTK can be regarded as an established alternative to preservation with University of Wisconsin (UW) solution when preservation times are short. Definitive assessment of the efficacy of preservation solutions requires further prospective randomised clinical trials that compare HTK and UW.