Ischemic preconditioning protects against cold ischemic injury through an oxidative stress dependent mechanism.
OBJECTIVE
Ischemic injury in cold preserved livers is characterized by sinusoidal endothelial cell (SEC) detachment and matrix metalloproteinase activity. Upon reperfusion reversible ischemic injury becomes permanent with SEC rapidly undergoing apoptosis. Ischemic preconditioning prevents reperfusion injury after normothermic ischemia. We hypothesized that ischemic preconditioning, through an oxygen free radical burst, protects against injury during cold preservation and reperfusion.


METHODS
Ischemic preconditioning was achieved in rats by clamping blood supply to the left and median lobes for 10 min followed by 15 min of reperfusion prior to preservation in cold University of Wisconsin solution for 30 h. In a second set of experiments, rats were pretreated with N-acetyl-cysteine (NAC). SEC apoptosis upon reperfusion was assessed in an isolated perfused rat liver (IPRL) model.


RESULTS
SEC detachment and activities of matrix metalloproteinase were significantly reduced in preconditioned livers. A decrease of SEC apoptosis after 1h of reperfusion in the IPRL was noted in preconditioned livers compared to controls. Pretreatment with NAC reversed the beneficial effects of ischemic preconditioning on SEC detachment and apoptosis.


CONCLUSIONS
Ischemic preconditioning is an effective strategy to prevent injury during cold preservation and after reperfusion. The protective effect is possibly mediated by oxygen free radicals.
Sindram
David
D
Hepatobiliary and Liver Transplant Laboratory, Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Rüdiger
Hannes A
HA
Upadhya
Aravinda G
AG
Strasberg
Steven M
SM
Clavien
Pierre Alain
PA
D000818:Animals; D017209:Apoptosis; D003080:Cold Temperature; D015925:Cryopreservation; D019194:Ischemic Preconditioning; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*