Background: Marginal pancreases with long ischemia time could implement the supply in organs for islet transplantation. To preserve islet in this kind of pancreas the strategy of remote ischemia/reperfusion preconditioning could be used. Remote preconditioning consists in the induction of ischemia and reperfusion episodes to another organ, which enhances the release of protective factor in the general circulation has been shown to have beneficial effect on the heart or the brain. Therefore, the aim of this work is to precondition the pancreas by muscle ischemia in order to preserve pancreases with long cold ischemia time (18h) using islet transplantation as a proof of concept of the efficacy of the preconditioning methods studied.
Methods: On the right inferior limb of Wistar rat (150-200g), a tourniquet was placed. Different times of ischemia were tested: 45 min, 1h, 1h30. Rat pancreases were stored in cold University of Wisconsin (UW) preservation solution for long cold ischemia times (18 hours). Pancreases biopsies were taken before performing islet isolation and ATP, lactate content was analyzed and TUNEL staining performed. Islet number and function were assessed straight after isolation.
Results: Despite no incidence of the different ischemia time on the lactate or ATP levels in the pancreatic tissue, TUNEL staining was less important in all conditions than in control. Regarding, islet isolation outcomes, 1h30 of ischemia pre-conditioning induced an increase in islet yield (406±50 IEQ/pancreas, p=0.069) as compared to control (257±57 IEQ/pancreas), with the rescue of large islets. Glucose stimulated-insulin secretion was improved by a 1h30 ischemia preconditioning (5,36 ± 2,11 µg/mL) as compared to control (2,05 ± 1,23 µg/mL).
Conclusion: Our preliminary results indicate that pre-conditioning of the pancreas could improve islet yields and islet functionality, and decrease apoptosis level. Pancreas pre-conditioning induced protection, but islet survival is depending on the type of ischemia-reperfusion cycle applied to the pancreas. In the aim of protecting pancreas and islets during a long time of cold ischemia, the duration and the number of cycles of ischemia-reperfusion need to be refined.