Einfluß der Thrombozyten-Endothelzell-Interaktion auf den hepatischen Ischämie-Reperfusionsschaden

Abstract

Background: In the recent literature, a potential role for platelets in the development of hepatic ischemia-reperfusion (I/R) injury has been discussed. The aim of this study was to investigate the impact of platelets on microvascular hepatic I/R injury using intravital microscopy. Methods: In C57BL/6 mice, an in situ ischemia of the left liver lobe was induced for 90 min. Platelets were separated from a syngeneic donor, labeled ex vivo using rhodamine 6G, and infused i.v. after 20 min of reperfusion. Leukocytes were stained by i.v. injection of rhodamine 6G. Platelet- and leukocyte-endothelial cell interactions were analyzed using intravital microscopy within identical postsinusoidal venules in a sham group, an I/R group, and an I/R group after i.v. administration of an anti-fibrinogen antibody (n = 7 each). For the determination of hepatocellular damage, the activities of AST and ALT were measured at the end of the experiment. Results: After 90 min of normothermic ischemia, numbers of permanently adherent platelets and leukocytes as well as liver enzyme activities were markedly increased. Administration of anti-fibrinogen antibody resulted in an attenuation of platelet adhesion, whereas the interaction of leukocytes with the postischemic endothelium was not affected. The activities of ALT and AST were significantly reduced compared to the non-treated group. Conclusion: Our data demonstrate that hepatic I/R induces platelet-endothelial cell interaction in postsinusoidal venules. The selective blockade of platelet adhesion preserved the cellular integrity of the liver. In conclusion, our results suggest that platelets play a critical role in hepatic I/R injury.