Pancreas storage in oxygenated perfluorodecalin does not restore post-transplant function of isolated pig islets pre-damaged by warm ischemia.

BACKGROUND: Cold storage in oxygenated perfluorodecalin (PFD) restores transplant function of ischemically damaged dog pancreata and reduces the impact of cold ischemia on recovery of isolated human islets. Whether PFD storage can improve islet isolation from pancreata exposed to significant warm i...

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Main Authors: Brandhorst, D, Iken, M, Bretzel, R, Brandhorst, H
Format: Journal article
Language:English
Published: 2006
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author Brandhorst, D
Iken, M
Bretzel, R
Brandhorst, H
author_facet Brandhorst, D
Iken, M
Bretzel, R
Brandhorst, H
author_sort Brandhorst, D
collection OXFORD
description BACKGROUND: Cold storage in oxygenated perfluorodecalin (PFD) restores transplant function of ischemically damaged dog pancreata and reduces the impact of cold ischemia on recovery of isolated human islets. Whether PFD storage can improve islet isolation from pancreata exposed to significant warm ischemia (WI) is unclear yet. The present study aimed to clarify this question in adult pigs. METHODS: After exsanguination, the intestine was removed immediately or left in the cavity for 30 min of WI. Resected pancreata were intraductally flushed with cold University of Wisconsin solution. Subsequently, pancreata were processed immediately by digestion-filtration (group I: 0 min WI, n=6; II: 30 min WI, n=6) or first stored for 3 h in oxygenated PFD (III: 0 min WI+PFD, n=5; IV: 30 min WI+PFD, n=6). RESULTS: Pancreata subjected to 30 min of WI yielded significantly less islets compared with the corresponding non-ischemic organs (I vs. II, P<0.01; III vs. IV, P<0.05). Oxygenation did not ameliorate the loss in islet yield (II vs. IV, NS). Ischemic islets were characterized by depleted ATP stores (388+/-73 (I) vs. 133+/-22 ng/1000 IEQ (II), P<0.01) and diminished insulin response to glucose calculated as stimulation index (SI; 2.47+/-0.36 (I) vs. 0.25+/-0.17 (II), P<0.05). PFD storage of ischemic organs partially restored ATP content (217+/-23 ng/1000 IEQ, II vs. IV, P<0.05) and glucose SI (1.60+/-0.09, II vs. IV, P<0.05) to a significant extent that reached the level of corresponding PFD-stored, non-ischemic pancreata (III vs. IV, NS). Sustained normoglycemia was exclusively observed in diabetic nude mice transplanted with islets isolated from non-ischemic organs. The significantly reduced graft function of ischemic islets (I vs. II, III vs. IV, P<0.001) was not increased by pancreatic oxygenation (II vs. IV, NS). CONCLUSIONS: The present study suggests that pancreas short-term storage in oxygenated PFD improves in vitro but not the in vivo function of ischemically damaged pig islets.
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spelling oxford-uuid:9de848f1-0bcc-4840-b5ed-a31925eaf4e52022-03-27T00:46:30ZPancreas storage in oxygenated perfluorodecalin does not restore post-transplant function of isolated pig islets pre-damaged by warm ischemia.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9de848f1-0bcc-4840-b5ed-a31925eaf4e5EnglishSymplectic Elements at Oxford2006Brandhorst, DIken, MBretzel, RBrandhorst, H BACKGROUND: Cold storage in oxygenated perfluorodecalin (PFD) restores transplant function of ischemically damaged dog pancreata and reduces the impact of cold ischemia on recovery of isolated human islets. Whether PFD storage can improve islet isolation from pancreata exposed to significant warm ischemia (WI) is unclear yet. The present study aimed to clarify this question in adult pigs. METHODS: After exsanguination, the intestine was removed immediately or left in the cavity for 30 min of WI. Resected pancreata were intraductally flushed with cold University of Wisconsin solution. Subsequently, pancreata were processed immediately by digestion-filtration (group I: 0 min WI, n=6; II: 30 min WI, n=6) or first stored for 3 h in oxygenated PFD (III: 0 min WI+PFD, n=5; IV: 30 min WI+PFD, n=6). RESULTS: Pancreata subjected to 30 min of WI yielded significantly less islets compared with the corresponding non-ischemic organs (I vs. II, P<0.01; III vs. IV, P<0.05). Oxygenation did not ameliorate the loss in islet yield (II vs. IV, NS). Ischemic islets were characterized by depleted ATP stores (388+/-73 (I) vs. 133+/-22 ng/1000 IEQ (II), P<0.01) and diminished insulin response to glucose calculated as stimulation index (SI; 2.47+/-0.36 (I) vs. 0.25+/-0.17 (II), P<0.05). PFD storage of ischemic organs partially restored ATP content (217+/-23 ng/1000 IEQ, II vs. IV, P<0.05) and glucose SI (1.60+/-0.09, II vs. IV, P<0.05) to a significant extent that reached the level of corresponding PFD-stored, non-ischemic pancreata (III vs. IV, NS). Sustained normoglycemia was exclusively observed in diabetic nude mice transplanted with islets isolated from non-ischemic organs. The significantly reduced graft function of ischemic islets (I vs. II, III vs. IV, P<0.001) was not increased by pancreatic oxygenation (II vs. IV, NS). CONCLUSIONS: The present study suggests that pancreas short-term storage in oxygenated PFD improves in vitro but not the in vivo function of ischemically damaged pig islets.
spellingShingle Brandhorst, D
Iken, M
Bretzel, R
Brandhorst, H
Pancreas storage in oxygenated perfluorodecalin does not restore post-transplant function of isolated pig islets pre-damaged by warm ischemia.
title Pancreas storage in oxygenated perfluorodecalin does not restore post-transplant function of isolated pig islets pre-damaged by warm ischemia.
title_full Pancreas storage in oxygenated perfluorodecalin does not restore post-transplant function of isolated pig islets pre-damaged by warm ischemia.
title_fullStr Pancreas storage in oxygenated perfluorodecalin does not restore post-transplant function of isolated pig islets pre-damaged by warm ischemia.
title_full_unstemmed Pancreas storage in oxygenated perfluorodecalin does not restore post-transplant function of isolated pig islets pre-damaged by warm ischemia.
title_short Pancreas storage in oxygenated perfluorodecalin does not restore post-transplant function of isolated pig islets pre-damaged by warm ischemia.
title_sort pancreas storage in oxygenated perfluorodecalin does not restore post transplant function of isolated pig islets pre damaged by warm ischemia
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