Ischämische Präkonditionierung führt zu einer Einschränkung der Leberregeneration nach ausgedehnter Hepatektomie

Abstract

Ischemic preconditioning (IPC) has been proven an effective strategy against hepatic ischemia-reper-fusion injury in both animal and human studies. However decreased protective effect was found in patients undergoing extended liver resection. The drastic reduction of the microvascular bed upon major hepatectomy is associated with exposure of remnant liver tissue to excessive portal perfusion. Herein, we demonstrate in a rat model of extended hepatectomy using laser Doppler flowmetry and in-vivo fluorescence microscopy that IPC causes microvascular hyperperfusion within the remnant liver. In addition to increased transaminase levels, IPC impaired hepatic proliferative response after organ resection, as indicated by both a significant reduction in mitotic figures and Ki-67 nuclear staining of hepatocytes as well as a decrease in restitution of liver mass. Thus in cases of drastic liver resection the remnant liver mass does not benefit from IPC-induced hyperperfusion as a trigger for proliferation, but rather suffers from shear stress-associated microvascular injury and reduced regen-erative capacity. Therefore, other strategies than IPC should be used to induce protection in extended liver resection.