Ultrastructural and Functional Alteration in Hepatic Sinusoidal Cells in Cold-Preserved Rat Liver

Summary

Tissue damage during cold preservation of a liver graft is a crucial problem in attempts to obtain better results in liver transplantation. This chapter describes the morphological and functional changes in sinusoidal endothelial cells (SEC), Kupffer cells, and those of fatty liver during cold preservation. We found apoptotic changes in SEC in cold-preserved liver, which seem to be one of the causative mechanisms of damage, in addition to the participation of activated Kupffer cells as described below. An enhancement of TNF-α-producing activity and asialo GM-1 expression was also observed, indicating Kupffer cell activation. In an experiment using GdCl₃, a potent inhibitor of Kupffer cell function, activated Kupffer cells were found to be strongly involved in SEC injury. This ultrastructural study with both SEM and TEM showed a prominent string-like appearance and detachment of the SEC processes after 24h preservation, whereas the SEC was better preserved in the GdCl₃-pretreated group. A study with microvascular casting also revealed that GdCl₃ contributed to the maintenance of SEC compared with the corresponding control, which showed an impairment in the radial arrangement and discontinuity of the sinusoid. These morphological changes may have a causative role in the microcirculatory disturbances in the liver, possibly inducing primary nonfunctioning graft. Furthermore, we clarified that SECs in fatty liver were very fragile and were progressively destroyed. Interestingly, we also found that fatty droplets expanded with an increase in the length of cold preservation.