Microcirculatory failure after rat liver transplantation is related to Kupffer cell-derived oxidant stress but not involved in early graft dysfunction

Background. Microcirculatory failure, activation of Kupffer cells (KC), and the formation of reactive oxygen species (ROS) are considered pivotal mech anisms of reperfusion injury after orthotopic liver transplantation. Howeve r, the sequence of these events and their impact on early graft function re main controversial. We therefore investigated whether KC induce microcircul atory disturbances through ROS release and whether microcirculatory failure contributes to early graft function after liver transplantation. Methods. Donor livers of Lewis rats were pretreated either with saline or w ith gadolinium chloride (GdCl3), an inhibitor of KC function (n=8 each). Sy ngeneic OLT was performed after 24 hr of hypothermic preservation in Univer sity of Wisconsin solution. Results. Intravital microscopy revealed significantly higher sinusoidal per fusion. rates in GdCl3-treated allografts (92 +/-1.1% vs. 75.7 +/-0.8%; P<0 .001) compared with untreated controls; permanent leukocyte sticking in sin usoids (23.5<plus/minus>2.1 vs. 62.6 +/-3.3 cells/lobule, P<0.001) and in p ostsinusoidal venules (153.1<plus/minus>10.4 vs. 446.6 +/- 46.4 cells/mm(2) , P<0.001) were markedly attenuated in GdCl3-treated allografts. Improvemen t of microcirculatory parameters in GdCl3-treated livers was correlated wit h a significant reduction of plasma glutathione disulfide formation by KC-d erived ROS (0.96<plus/minus>0.1 muM vs. 1.79 +/-0.5 muM; P<0.01). Despite t hese beneficial effects, GdCl3-pretreatment failed to improve postischemic alanine aminotransferase release and bile flow. Conclusions. Microcirculatory failure after liver transplantation is relate d to KC-derived oxidant stress but not involved in early graft dysfunction.