2017 - CIRTA


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10- Intestinal Transplantation

52.4 - Luminal preservation of the human small bowel graft reduces mucosal damage during cold storage

Presenter: Guido, Trentadue, Groningen, Netherlands
Authors: Guido Trentadue, Jasper van Praagh, Peter Olinga, Jan Willem Haveman, Klaas Nico Faber, Gerard Dijkstra

Luminal preservation of the human small bowel graft reduces mucosal damage during cold storage

Guido Trentadue1, Jasper van Praagh2, Peter Olinga2, Jan Willem Haveman3, Klaas Nico Faber1,4, Gerard Dijkstra1.

1Gastroenterology and Hepathology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; 2Pharmacy, Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, Netherlands; 3Surgery, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; 4Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

Introduction: Survival rates of small bowel (SB) grafts are the lowest among solid organ transplantations[1]. Unique for small bowel transplantation (SBx) is the presence of a large volume of metabolically-active luminal content consisting of a complex mixture of microbes, dietary and waste products. This luminal content may decrease mucosal integrity during preservation, which might lead to bacterial translocation and predispose for rejection of the graft. Cold storage of SB grafts is limited to a maximum of 10h after which it is deemed unsuitable for transplantation[2]. Luminal preservation (LP) with macrogol 4000 (polyethylene glycol, PEG) has shown promising effects in improving SB grafts in animal models[3][4]. We have started a project to analyse the effect of various luminally-applied solutions on cold storage-induced injury of the human SB. Here, we report our preliminary data.

Methods: So far, eight SB came available for this study from brain-dead donors. In all cases, standard vascular perfusion with ice-cold University of Wisconsin solution (UW) was performed. Five bowels served as a control group with no LP and after procurement, standard static cold storage on UW was performed. Three bowels were filled with 1.5 litres of PEG prior to procurement and cold storage. Tissue samples were taken at procurement, and after 7 and 14 hours of preservation in ice-cold UW. Jejunal and ileal samples were analysed for Park/Chiu score.

Results: Control samples show the natural decay of the graft’s structure. Median Park score for jejunum is 3 (maximum value=5), 4 (7) and 5 (5) in successive time points; for ileum is 0 (2), 3 (4) & 4 (7) respectively. Median Park score for jejunum is 1 (4), 3 (4) and 3.5 (4) in successive time points; for ileum is 1 (2), 3 (3) & 3 (3), respectively. Luminal preservation with PEG seems to maintain the epithelial lining, with increasing signs of edema of the villi between the lamina propria and the epithelium.

Conclusion: These preliminary data show that both jejunum and ileum with LP show a trend to maintain a low level of preservation injury during all time points, without significant increase in damage. LP might increase the graft preservation time window. Future analyses will be performed to study protein and bacterial location and gene expression. Additional luminal solutions will be studied, and an in vitro model for reperfusion will be performed to evaluate the risk of ischemia reperfusion injury.

[1] Grant D et al. Intestinal transplant registry report: global activity and trends. Am J Transplant. 2015; 15(1): 210-219.
[2] Oltean M et al. Intraluminal polyethylene glycol stabilizes tight junctions and improves intestinal preservation in the rat. Am J Transplant. 12(8):2044-2051.
[3] Roskott AM et al. Small bowel preservation for intestinal transplantation: a review. Transpl Int. 2011, 24(2):107-131.
[4] Oltean M et al. Organ-specific solutions and strategies for the intestinal preservation. Int Rev Immunol. 2014, 33(3):234-244.


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