MONITORING OF MICROHEMODYNAMIC CHANGES DURING EX-VIVO XENOGENEIC LIVER PERFUSION USING INTRAVITAL MICROSCOPY

The main targets of xenogeneic rejection mechanisms are the endothelia l cells of the graft. Their activation and the consequent alteration o f the organ's microcirculation lead to the destruction of the xenograf t. Microhemodynamic changes occurring during this process are still po orly characterized. The aim of this study was to analyze the microcirc ulation during xenogeneic ex vivo hemoperfusion of rat livers and to m onitor the impact of treatment strategies using intravital fluorescenc e microscopy. In contrast to the isogeneic control group, blood flow a lmost completely stopped within the first minutes of xenoperfusion. Si multaneously, perfusion pressure increased and bile production was red uced. Acetylsalicylate (Aspisol) and-the platelet-activating factor an tagonist WEB 2170 improved the microcirculation and function of the xe noperfused liver. The combination showed a synergistic effect. After a pheresis of preformed xenogeneic antibodies, the parameters measured w ere comparable with those seen in isogeneic experiments. Complement de gradation with cobra venom factor revealed a minor improvement in perf usion. A rapid, extensive, and irreversible leukocyte accumulation in terminal portal vessels was observed in all xenogeneic experiments. Bl ood counts of the perfusate confirmed the early trapping of leukocytes and platelets in the xenoperfused liver, indicating nonimmunological, cellular involvement in this rejection process.