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Beneficial Effects of Ischemic Preconditioning on Pancreas Cold Preservation
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
Source: Cell Transplantation
Publisher: Cognizant Communication Corporation
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Abstract:
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-hrs of cold preservation before assessment of organ injury or islet isolation. Pancreas IPC improved islet yields (964±336 vs. 711±204IEQ/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 vs. 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 (>2-fold-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.Document Type:
DOI: http://dx.doi.org/10.3727/096368911X623853
Appeared or available online: February 2, 2012
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