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 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.
Diabetes Research Institute, University of Miami, Miami, FL 33136, USA.
Anthony R
AR
Hogan
Marco
M
Doni
R Damaris
RD
Molano
Melina M
MM
Ribeiro
Angela
A
Szeto
Lorenzo
L
Cobianchi
Elsie
E
Zahr-Akrawi
Judith
J
Molina
Alessia
A
Fornoni
Armando J
AJ
Mendez
Camillo
C
Ricordi
Ricardo L
RL
Pastori
Antonello
A
Pileggi
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D005786:Gene Expression Regulation; D019194:Ischemic Preconditioning; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019255:NADPH Oxidases / Q000378:metabolism; D009926:Organ Preservation; D018384:Oxidative Stress; D010179:Pancreas / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew
D001786:Blood Glucose; D019255:NADPH Oxidases