T Asakura

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.

Changes of serum cytokines associated with hepatic regeneration after living-related liver transplantation

IN CLINICAL orthotopic liver transplantation, the graft frequently deteriorates due to various mechanisms, including preservation injury, warm ischemia during implantation, and reperfusion injury. After hepatocyte damage, some cytokines stimulate hepatocytes and play key roles in the regulation of hepatic regeneration. In livingrelated liver transplantation (LRLT), we often must use partial livers, which are smaller than the standard liver volume of recipients. After transplantation, the size of the partial liver graft increases rapidly in a short period of time. During graft enlargement, it is believed that changes of serum cytokines reflect the status of the regeneration process of the liver graft. In this study, we measured serum cytokines that play a the role in the regulation of liver regeneration, (ie, hepatocyte growth factor [HGF], interleukin-6 [IL-6], and transforming growth factor-b1 [TGFb1]. The purpose of this study was to investigate the relationship between changes of serum cytokine levels and growth of the graft, as well as recovery from graft damage.

Arterial reconstruction using vein graft from the common iliac artery after hepatic artery thrombosis in living-related liver transplantation.

VASCULAR complications in liver transplantation sometimes occur and may be lethal both for the transplant graft and the patient. Thrombosis at the anastomosis of the hepatic artery is the most common complication in children. Several methods of hepatic arterial reconstruction have been reported, including use of recipient splenic artery, interposition of vessel graft between common hepatic artery and graft artery, and use of conduit between aorta and the graft. We report herein the case of a patient with hepatic arterial reconstruction using vein graft between the common iliac artery and the graft artery after hepatic artery thrombosis in living-related liver transplantation.

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.