Ischemic preconditioning and liver tolerance to warm or cold ischemia: experimental studies in large animals.
BACKGROUND
In the rodent, ischemic preconditioning (IPC) has been shown to improve the tolerance of the liver to ischemia-reperfusion under normothermic or hypothermic conditions. The aim of the present study was to test this hypothesis in a dog model, which may be more relevant to the human.


METHODS
Beagle dogs were used in two distinct animal models of hepatic warm ischemia and orthotopic liver transplantation (hypothermic ischemia). IPC consisted of 10 minutes of ischemia followed by 10 minutes of reperfusion. In the first model, livers were exposed to 55 minutes prolonged warm ischemia and reperfused for 3 days (n = 6). In the second model, livers were retrieved and preserved for 48 hours at 4 degrees C in University of Wisconsin solution, transplanted, and reperfused without immunosuppression for 7 days (n = 5). In each model, nonpreconditioned animals served as controls (n = 5 in each group). Also, isolated dog hepatocytes were subjected to warm and cold storage ischemia-reperfusion to model the animal transplant studies using IPC.


RESULTS
In the first model (warm ischemia), IPC significantly decreased serum aminotransferase activity at 6 and 24 hours post-reperfusion. After 1 hour of reperfusion, preconditioned livers contained more adenosine triphosphate and produced more bile and less myeloperoxidase activity (neutrophils) relative to controls. In the second model (hypothermic preservation), IPC was not protective. Finally, IPC significantly attenuated hepatocyte cell death after cold storage and warm reperfusion in vitro.


CONCLUSIONS
IPC is effective in large animals for protecting the liver against warm ischemia-reperfusion injury but not injury associated with cold ischemia and reperfusion (preservation injury). However, the IPC effect observed in isolated hepatocytes suggests that preconditioning for preservation is theoretically possible.
Compagnon
Philippe
P
Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine, Madison, WI 53792, USA.
Lindell
Susanne
S
Ametani
Mary S
MS
Gilligan
Barbara
B
Wang
Hong-Bing
HB
D'Alessandro
Anthony M
AM
Southard
James H
JH
Mangino
Martin J
MJ
D000222:Adaptation, Physiological; D000818:Animals; D002470:Cell Survival; D015925:Cryopreservation; D004285:Dogs; D005260:Female; D022781:Hepatocytes / Q000502:physiology; D006358:Hot Temperature; D007511:Ischemia / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply* / Q000503:physiopathology; D016031:Liver Transplantation; D009926:Organ Preservation / Q000009:adverse effects; D015424:Reperfusion; D015427:Reperfusion Injury / Q000517:prevention & control