Cold-storage injury to rat small-bowel transplants – beneficial effect of a modified HTK solution

Background The small bowel is prone to ischaemic injury during transport prior to 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 ischaemic 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 following 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. Received 15 December 2017. Revision received 31 May 2018. Accepted 3 June 2018. *deceased Address for correspondence: Dr Gesine Pless-Petig, Institut für Physiologische Chemie, Universitätsklinikum Essen, Hufelandstr. 55, 45122 Essen. gesine.pless@uni-duisburg-essen.de Authorship statement I. Lautenschläger participated in research design, writing the paper, research work and data analysis G. Pless-Petig participated in writing the paper and data analysis P. Middel participated in research work and data analysis H. de Groot participated in research design U. Rauen participated in research design, writing the paper and data analysis T. Stojanovic participated in research design, writing the paper, research work and data analysis Disclosure U. Rauen obtained consulting fees from Dr Franz Köhler Chemie GmbH, Bensheim, Germany. Dr F. Köhler Chemie holds a patent on a preservation solution covering the modified solution used in this study, and U. Rauen is one of the inventors of the solution. Funding The work was partially funded by Dr F. Köhler Chemie GmbH. However, the study design and data interpretation were nDrever influenced by the company at any point in time, which was also stipulated and agreed upon in the funding contract. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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