Spezielle aspekte des ischämie-/reperfusionsschadens bei der leber

The clinical relevance of ischemia-/reperfusion injury still remains evident due to its strong association with both poor initial graft function and primary nonfunction after liver transplantation. Numerous experimental and clinical studies revealed that activated Kupffer cells play a pivotal role for the development of this phenomenon; however, the exact underlying mechanism of reperfusion injury remains unclear. Disturbances of the hepatic microcirculation combined with cellular interaction between platelets, leukocytes and endothelial lining cells plus various Kupffer cell-derived proinflammatory mediators, such as TNFα, IL-1 and free radicals, and the expression of adhesion molecules are further essential determinants of pathophysiological changes during reperfusion injury. It has been conclusively demonstrated that reperfusion injury rather than ischemic cell damage developing during cold storage predominates. Further, beside donor-dependent factors, i.e. steatosis, surgical organ manipulation during harvest, which is inevitable with standard harvesting techniques, can be detrimental for viability of the graft most likely due to activation of Kupffer cells. Underlying mechanisms include disturbances of the hepatic microcirculation, autonomous nerve system and metabolic changes. During the last decade a large variety of experimental approaches have been developed to prevent reperfusion injury. Today, clinical trials are warranted to confirm the most promising therapeutic concepts.