Beneficial Effects of Ischemic Preconditioning on Pancreas Cold Preservation

Ischemic preconditioning (IPC) confers tissue resistance to subsequent ischemia in several organs. The protective effects are obtained by applying short periods of warm ischemia followed by reperfusion prior to extended ischemic insults to the organs. In the present study, we evaluated whether IPC c...

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Main Authors: Anthony R. Hogan, Marco Doni, R. Damaris Molano, Melina M. Ribeiro, Angela Szeto, Lorenzo Cobianchi, Elsie Zahr-Akrawi, Judith Molina, Alessia Fornoni, Armando J. Mendez, Camillo Ricordi, Ricardo L. Pastori, Antonello Pileggi M.D., Ph.D.
Format: Article
Language:English
Published: SAGE Publishing 2012-07-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368911X623853
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author Anthony R. Hogan
Marco Doni
R. Damaris Molano
Melina M. Ribeiro
Angela Szeto
Lorenzo Cobianchi
Elsie Zahr-Akrawi
Judith Molina
Alessia Fornoni
Armando J. Mendez
Camillo Ricordi
Ricardo L. Pastori
Antonello Pileggi M.D., Ph.D.
author_facet Anthony R. Hogan
Marco Doni
R. Damaris Molano
Melina M. Ribeiro
Angela Szeto
Lorenzo Cobianchi
Elsie Zahr-Akrawi
Judith Molina
Alessia Fornoni
Armando J. Mendez
Camillo Ricordi
Ricardo L. Pastori
Antonello Pileggi M.D., Ph.D.
author_sort Anthony R. Hogan
collection DOAJ
description Ischemic preconditioning (IPC) confers tissue resistance to subsequent ischemia in several organs. The protective effects are obtained by applying short periods of warm ischemia followed by reperfusion prior to extended ischemic insults to the organs. In the present study, we evaluated whether IPC can reduce pancreatic tissue injury following cold ischemic preservation. Rat pancreata were exposed to IPC (10 min of warm ischemia followed by 10 min of reperfusion) prior to ~18 h of cold preservation before assessment of organ injury or islet isolation. Pancreas IPC improved islet yields (964 ± 336 vs. 711 ± 204 IEQ/pancreas; p = 0.004) and lowered islet loss after culture (33 ± 10% vs. 51 ± 14%; p = 0.0005). Islet potency in vivo was well preserved with diabetes reversal and improved glucose clearance. Pancreas IPC reduced levels of NADPH-dependent oxidase, a source of reactive oxygen species, in pancreas homogenates versus controls (78.4 ± 45.9 vs. 216.2 ± 53.8 RLU/μg; p = 0.002). Microarray genomic analysis of pancreata revealed upregulation of 81 genes and downregulation of 454 genes (greater than twofold change) when comparing IPC-treated glands to controls, respectively, and showing a decrease in markers of apoptosis and oxidative stress. Collectively, our study demonstrates beneficial effects of IPC of the pancreas prior to cold organ preservation and provides evidence of the key role of IPC-mediated modulation of oxidative stress pathways. The use of IPC of the pancreas may contribute to increasing the quality of donor pancreas for transplantation and to improving organ utilization.
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spelling doaj.art-cb74aa5742084858a7378166c20caf262022-12-22T01:26:52ZengSAGE PublishingCell Transplantation0963-68971555-38922012-07-012110.3727/096368911X623853Beneficial Effects of Ischemic Preconditioning on Pancreas Cold PreservationAnthony R. Hogan0Marco Doni1R. Damaris Molano2Melina M. Ribeiro3Angela Szeto4Lorenzo Cobianchi5Elsie Zahr-Akrawi6Judith Molina7Alessia Fornoni8Armando J. Mendez9Camillo Ricordi10Ricardo L. Pastori11Antonello Pileggi M.D., Ph.D.12 DeWitt-Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Pavia, IRCCS Fondazione “San Matteo” Hospital, Pavia, Italy Diabetes Research Institute, University of Miami, Miami, FL, USA Diabetes Research Institute, University of Miami, Miami, FL, USA Diabetes Research Institute, University of Miami, Miami, FL, USA Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Pavia, IRCCS Fondazione “San Matteo” Hospital, Pavia, Italy Diabetes Research Institute, University of Miami, Miami, FL, USA Diabetes Research Institute, University of Miami, Miami, FL, USA Division of Nephrology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA Division of Endocrinology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA Department of Biomedical Engineering, University of Miami, Miami, FL, USA Division of Endocrinology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA Department of Microbiology and Immunology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USAIschemic preconditioning (IPC) confers tissue resistance to subsequent ischemia in several organs. The protective effects are obtained by applying short periods of warm ischemia followed by reperfusion prior to extended ischemic insults to the organs. In the present study, we evaluated whether IPC can reduce pancreatic tissue injury following cold ischemic preservation. Rat pancreata were exposed to IPC (10 min of warm ischemia followed by 10 min of reperfusion) prior to ~18 h of cold preservation before assessment of organ injury or islet isolation. Pancreas IPC improved islet yields (964 ± 336 vs. 711 ± 204 IEQ/pancreas; p = 0.004) and lowered islet loss after culture (33 ± 10% vs. 51 ± 14%; p = 0.0005). Islet potency in vivo was well preserved with diabetes reversal and improved glucose clearance. Pancreas IPC reduced levels of NADPH-dependent oxidase, a source of reactive oxygen species, in pancreas homogenates versus controls (78.4 ± 45.9 vs. 216.2 ± 53.8 RLU/μg; p = 0.002). Microarray genomic analysis of pancreata revealed upregulation of 81 genes and downregulation of 454 genes (greater than twofold change) when comparing IPC-treated glands to controls, respectively, and showing a decrease in markers of apoptosis and oxidative stress. Collectively, our study demonstrates beneficial effects of IPC of the pancreas prior to cold organ preservation and provides evidence of the key role of IPC-mediated modulation of oxidative stress pathways. The use of IPC of the pancreas may contribute to increasing the quality of donor pancreas for transplantation and to improving organ utilization.https://doi.org/10.3727/096368911X623853
spellingShingle Anthony R. Hogan
Marco Doni
R. Damaris Molano
Melina M. Ribeiro
Angela Szeto
Lorenzo Cobianchi
Elsie Zahr-Akrawi
Judith Molina
Alessia Fornoni
Armando J. Mendez
Camillo Ricordi
Ricardo L. Pastori
Antonello Pileggi M.D., Ph.D.
Beneficial Effects of Ischemic Preconditioning on Pancreas Cold Preservation
Cell Transplantation
title Beneficial Effects of Ischemic Preconditioning on Pancreas Cold Preservation
title_full Beneficial Effects of Ischemic Preconditioning on Pancreas Cold Preservation
title_fullStr Beneficial Effects of Ischemic Preconditioning on Pancreas Cold Preservation
title_full_unstemmed Beneficial Effects of Ischemic Preconditioning on Pancreas Cold Preservation
title_short Beneficial Effects of Ischemic Preconditioning on Pancreas Cold Preservation
title_sort beneficial effects of ischemic preconditioning on pancreas cold preservation
url https://doi.org/10.3727/096368911X623853
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