Brief periods of tissue
ischemia produced tissue resistance to prolonged
ischemia and reperfusion, a phenomenon called ischemic preconditioning. The mechanisms of ischemic preconditioning were examined in a rat
warm ischemia-reperfusion model as well as the effect of ischemic preconditioning on liver regeneration. Ischemic preconditioning decreased liver injury after
warm ischemia-reperfusion, which was reversed by Kupffer cell depletion. Ischemic preconditioning stimulated Kupffer cells to produce
reactive oxygen species. Scavengers of
reactive oxygen species reversed the effect of ischemic preconditioning, and pretreatment with sublethal dose of
hydrogen peroxide mimicked ischemic preconditioning effect. Rat livers were preconditioned by
ischemia and subjected to 70% partial
hepatectomy. Liver regeneration was then evaluated serially. Ischemic preconditioning promoted liver regeneration, which was reversed by
adenosine A2 receptor antagonism and mimicked by
adenosine A2 receptor agonism. Promotion of liver regeneration by ischemic preconditioning and
adenosine A2 receptor agonism were reversed by Kupffer cell depletion. In conclusion, ischemic preconditioning stimulates Kupffer cells to produce
reactive oxygen species, leading to hepatocyte protection against
warm ischemia-
reperfusion injury; and ischemic preconditioning promoted liver regeneration via
adenosine A2 receptor pathway in Kupffer cells.