FLUORESCENCE VIDEOMICROSCOPIC ASSESSMENT OF XENOGENEIC MICROCIRCULATION AND IMPACT OF ANTIBODY REMOVAL BY IMMUNOADSORPTION

Background. Alterations in microcirculation are considered central to the pathogenesis of hyperacute xenogeneic rejection (HXR) of vascuIari zed xenografts, but currently there exist no data describing these mic rohemodynamic alterations. Methods. Rat livers were perfused in situ w ith either isogeneic rat blood or xenogeneic human blood. The microcir culation of these xenoperfused livers was investigated directly using intravital fluorescence microscopy, and compared with that of isogenei c hemoperfused livers. In addition, the impact of antibody depletion b y immunoadsorption was investigated. Results. Although a homogenous mi crocirculation was found during isogeneic liver perfusion (index of ac inar perfusion 90.4%/sinusoidal perfusion rate 93.6%), xenoperfusion r esulted in a rapid breakdown of the microcirculation (47.5%/67.1%, res pectively), Perfusion deficits were found predominantly in the peripor tal areas. Immunoadsorption reduced the total amount of IgM and IgG by 75.2% and 96.2%, respectively, and caused a significantly improved li ver perfusion (80.2%/84.4%) and liver function, as indicated by bile p roduction. In contrast, the massive hepatic leukocyte and platelet acc umulation observed during perfusion with untreated xenogeneic blood wa s not altered by antibody depletion. Conclusions. Thus, the combinatio n of isolated rat liver perfusion and intravital fluorescence microsco py enables the observation and quantification of the early phase of HX R. This is an important step forward for sensitive characterization of the rejection process and will enable the mechanisms involved in HXR to be elucidated Antibody depletion was shown to improve liver functio n and perfusion, but did not, reconstitute liver viability to the leve l of the isogeneic perfusion. These findings highlight the need for ad ditional therapeutic regimens in xenografting.