hypoxia of the growing liver accelerates regeneration background after portal vein ligation of 1 side of the liver the other side regenerates at a slow rate this slow growth may be accelerated to rapid growth by adding a transection between the 2 sides ie performing portal vein ligation and parenchymal transection we found that in patients undergoing portal vein ligation and parenchymal transection portal vein hyperflow in the regenerating liver causes a significant reduction of arterial flow due to the hepatic arterial buffer response we postulated that the reduction of arterial flow induces hypoxia in the regenerating liver and used a rat model to assess hypoxia and its impact on kinetic growthmethods a rat model of rapid portal vein ligation and parenchymal transection and slow regeneration portal vein ligation was established portal vein flow and pressure data were collected liver regeneration was assessed in rats using computed tomography proliferation with ki67 and hypoxia with pimonidazole and hif1 stainingresults the rat model confirmed acceleration of regeneration in portal vein ligation and parenchymal transection as well as the portal vein hyperflow seen in patients additionally tissue hypoxia was observed after portal vein ligation and parenchymal transection while little hypoxia staining was detected after portal vein ligation to determine if hypoxia is a consequence or an inciting stimulus of rapid liver regeneration we used a prolylhydroxylase blocker to activate hypoxia signaling pathways in the slow model this clearly accelerated slow to rapid liver regeneration inversely abrogation of hypoxia led to a blunting of rapid growth to slow growth the topical application of prolylhydroxylase inhibitors on livers in rats induced spontaneous areas of regenerationconclusion this study shows that pharmacologically induced hypoxic signaling accelerates liver regeneration similar to portal vein ligation and parenchymal transection hypoxia is likely an accelerator of liver regeneration also prolylhydroxylase inhibitors may be used to enhance liver regeneration pharmaceutically