Ischemic preconditioning of rat livers against cold storage-reperfusion injury: Role of nonparenchymal cells and the phenomenon of heterologous preconditioning

Brief periods of ischemia followed by reperfusion render tissues resistant against subsequent prolonged ischemia, a phenomenon called ischemic precond itioning, The effect of ischemic preconditioning on liver transplantation w as investigated in relation to sinusoidal endothelial cell injury and Kupff er-cell activation, which are prominent features of storage and reperfusion injury leading to liver graft failure, Rat livers were preconditioned by 5 or 10 minutes of ischemia and 5 minutes of reperfusion and stored in Unive rsity of Wisconsin (UW) solution for 30 hours. Livers were then reperfused for 15 minutes with physiological buffer containing trypan blue, Under thes e conditions, injury occurs predominantly to sinusoidal endothelial cells, reflected by trypan blue staining of nonparenchymal cells in histological s ections, Ischemic preconditioning decreased nonparenchymal cell killing by more than 50%, When half the liver was preconditioned, sinusoidal endotheli al cells were also protected in the contralateral half. Other stored livers were reperfused with nitroblue tetrazolium, which is converted to insolubl e formazan by superoxide radicals. Ischemic preconditioning decreased the i ntensity of formazan deposition over Kupffer cells, Finally, stored livers were transplanted into nontreated rats, Ischemic preconditioning improved r ecipient long-term survival after 30 hours of cold ischemic storage in UW s olution from 30% to 80% and decreased serum tumor necrosis factor-alpha lev els in posthepatic blood 4 hours postoperatively from 98 to 54 pg/mL, In co nclusion, ischemic preconditioning protects sinusoidal endothelial cells an d suppresses Kupffer-cell activation after storage and reperfusion, As a re sult, graft survival im-proves after liver transplantation. Moreover, ische mia to half the liver confers protection to the other half Such heterologou s preconditioning provides a new means to protect liver tissue against isch emia-reperfusion injury without imposing ischemia on the target tissue.