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 degrees C and a rate of 0.5 mL/g(-1) min(-1) while the preservation solution was oxygenated with 100% O(2). 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 microM deferoxamine + 2.5 microM (Custodiol-N, 2.5) or 7.5 microM (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 degrees 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 C0(2), 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. Copyright 2010 Elsevier Inc. All rights reserved.
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 degrees C and a rate of 0.5 mL/g(-1) min(-1) while the preservation solution was oxygenated with 100% O(2). 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 microM deferoxamine + 2.5 microM (Custodiol-N, 2.5) or 7.5 microM (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 degrees 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 C0(2), 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. Copyright 2010 Elsevier Inc. All rights reserved.
Authors: Michael B Sano; Robert E Neal; Paulo A Garcia; David Gerber; John Robertson; Rafael V Davalos Journal: Biomed Eng Online Date: 2010-12-10 Impact factor: 2.819
Authors: Mindaugas Kvietkauskas; Bettina Leber; Kestutis Strupas; Philipp Stiegler; Peter Schemmer Journal: Front Immunol Date: 2020-02-27 Impact factor: 7.561