J Takayama

Elimination of Kupffer cells and nafamostat mesilate rinse prevent reperfusion injury in liver grafts from agonal non-heart-beating donors.

BACKGROUND We hypothesized that microcirculatory disturbance was an obstacle to liver transplantation (LTx) from non-heart-beating donors (NHBDs) and that it was attributed mainly to a deterioration of sinusoidal endothelial cells (SECs) and sinusoidal narrowing. This study was designed to examine porcine orthotopic LTx using livers obtained from pretreated agonal NHBDs, and to determine whether the maintenance of the liver microcirculation would result in successful LTx from agonal NHBDs. METHODS Pigs were allocated to five groups: (i) control group; (ii) NM group, in which grafts were rinsed with nafamostat mesilate (NM) rinse; (iii) LD group, in which Kupffer cells in grafts were eliminated by liposome-encapsulated dichloromethylene diphosphonate (L-DMDP); (iv) LDNM group, in which grafts pretreated with L-DMDP were rinsed with NM rinse; (v) heart-beating donor (HBD) group. In all groups, but the HBD group, the livers were pretreated with FK506 and prostaglandin I2 analogue, and were preserved in University of Wisconsin solution after cardiac arrest. Thereafter orthotopic LTx was performed. RESULTS After reperfusion, it was histologically demonstrated that elimination of Kupffer cells prevented SECs deterioration and NM rinse prevented sinusoidal narrowing. The hepatic energy charge recovered in all groups except the control group. In the LDNM group, three of four recipients survived more than 7 days. CONCLUSIONS For a successful LTx from agonal NHBDs, it is important to prevent microcirculatory disturbance caused by SEC deterioration and sinusoidal narrowing after reperfusion. Combination therapy consisting in the elimination of Kupffer cells and NM rinse prevented primary graft non-function in liver grafts from agonal NHBDs.

Elimination of kupffer cells and administration of protease inhibitor improve graft viability and prevent reperfusion injury In NHBD

T HE SHORTAGE of donors has become a serious problem in liver transplantation (LTX). IF the liver graft from a non-heartbeating donor (NHBD) was available for LTX, the supply could be improved. But a liver graft from NHBD has not been suitable for LTX because the graft viability is deteriorated by warm ischemic injury and severe reperfusion injury. Over the past few years a considerable number of studies has been done on the mechanisms of warm ischemic injury and reperfusion injury. Many agents effective for these injuries, have also been reported. The aim of this study is to determine whether liver grafts from NHBD are suitable for clinical LTX.

New strategy for liver transplantation from non-heart-beating donors.

THE shortage of donors has become a serious problem in liver transplantation (LTx). LTx from controlled non-heart-beating donors (NHBD) has been attempted. However, it has been reported that the grafts from NHBD develop primary graft nonfunction more often than those from heart-beating donors. The aim of this study was to discover a safer method to prevent ischemia and reperfusion injuries in liver grafts from NHBD.