Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-02-04

AUTHORS

Alice Faure, Laurie Bruzzese, Jean-Guillaume Steinberg, Yves Jammes, Julia Torrents, Stephane V. Berdah, Emmanuelle Garnier, Tristan Legris, Anderson Loundou, Matthieu Chalopin, Guy Magalon, Regis Guieu, Emmanuel Fenouillet, Eric Lechevallier

ABSTRACT

BACKGROUND: In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold-storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold-preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. METHODS: The preservation solution Celsior saturated with pure argon (Argon-Celsior) or xenon (Xenon-Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air-Celsior). The left kidney was removed, and Air-Celsior (n = 8 pigs), Argon-Celsior (n = 8) or Xenon-Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air-Celsior was used. Heterotopic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. RESULTS: The use of Argon-Celsior vs. Air-Celsior: (1) improved function recovery as monitored via creatinine clearance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2-3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day-21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the "reduced ascorbic acid/thiobarbituric acid reactive substances" ratio and Hsp27 expression; (6) limited the inflammatory response as shown by expression of TNF-alpha, IL1-beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon-Celsior was detrimental, no animal surviving by day-8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group. CONCLUSIONS: The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation. More... »

PAGES

40

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12967-016-0795-y

DOI

http://dx.doi.org/10.1186/s12967-016-0795-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021998215

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26847569


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28 schema:description BACKGROUND: In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold-storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold-preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. METHODS: The preservation solution Celsior saturated with pure argon (Argon-Celsior) or xenon (Xenon-Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air-Celsior). The left kidney was removed, and Air-Celsior (n = 8 pigs), Argon-Celsior (n = 8) or Xenon-Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air-Celsior was used. Heterotopic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. RESULTS: The use of Argon-Celsior vs. Air-Celsior: (1) improved function recovery as monitored via creatinine clearance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2-3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day-21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the "reduced ascorbic acid/thiobarbituric acid reactive substances" ratio and Hsp27 expression; (6) limited the inflammatory response as shown by expression of TNF-alpha, IL1-beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon-Celsior was detrimental, no animal surviving by day-8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group. CONCLUSIONS: The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation.
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36 Argon-Celsior
37 Celsior
38 Current static preservation procedures
39 HSP27 expression
40 IL6
41 Organoprotective strategies
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43 Xenon-Celsior
44 acid reactive substances
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46 air
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59 composition
60 conditions
61 context
62 contralateral nephrectomy
63 creatinine clearance
64 day 8
65 days
66 death/euthanasia
67 defense
68 diuresis recovery 2
69 duration
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71 effect
72 effect of argon
73 effectiveness
74 euthanasia
75 expression
76 fibrosis
77 fraction
78 function recovery
79 functional recovery
80 gas composition
81 gases
82 graft preservation
83 graft quality
84 group
85 heterotopic autotransplantation
86 immersion
87 inflammation
88 inflammation response
89 inflammatory response
90 influence function recovery
91 injury
92 interstitial fibrosis
93 ischemic injury
94 kidney
95 kidney transplantation
96 left kidney
97 medium
98 model
99 natural death/euthanasia
100 necrosis
101 nephrectomy
102 noble gases
103 organ preservation
104 pig model
105 plasma antioxidant defenses
106 positive effect
107 preclinical pig model
108 preservation
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110 preservation procedures
111 preservation solution Celsior
112 pressure
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115 properties
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123 renal tissue properties
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140 tissue properties
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362 Department of Plastic Surgery, Aix-Marseille University, APHM, Marseille, France
363 Department of Urology and Kidney Transplantation, Aix-Marseille University, APHM, Marseille, France
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369 Department of Plastic Surgery, Aix-Marseille University, APHM, Marseille, France
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