The effects of the elimination of Kupffer cells in the isolated perfused liver from non-heart-beating rat.

We examined the effect of elimination of Kupffer cells on the sinusoidal microcirculation in graft harvested from non-heart-beating donors (NHBD), focusing on the arachidonic acid cascade and cytokines. Cardiac arrest was induced by thoracotomy. Livers were harvested 30 min after thoracotomy and perfused by Krebs-Henseleit bicarbonate buffer for 60 min after 6 h cold preservation. For the elimination of Kupffer cells, rats were pretreated liposome-encapsulated dichloromethylene diphosphonate (KE group). Eicosanoids (TXB2, 6-keto-PGF1alpha, LTB4) and cytokines (TNFalpha, IL-1beta) in the perfusate were measured. Histological examination was also carried out. In the KE group, the value of TXB2 was suppressed completely and cytokines were reduced, and sinusoidal structures and hepatocytes were well protected. These results indicated that the elimination of Kupffer cells improved sinusoidal microcirculation in NHBD and liver transplantation using grafts from NHBD could be made to succeed by modulation of Kupffer cells.