摘要:

AbstractIn rat models of liver preservation, the primary event leading to liver graft failure after cold storage is a reperfusion injury causing damage to sinusoidal endothelial cells and activation of Kupffer cells (KC). After storage for longer than 16 h in University of Wisconsin solution, reperfusion induces rapid endothelial cell killing. Kupffer cell activation also occurs as indicated by cell surface ruffling, degranulation, release of hydrolytic enzymes, generation of oxygen radicals, and increased phagocytosis. Down‐regulation of KC activity with nisoldipine or pentoxifylline improves graft survival. Moreover, pretreatment of donors with small amounts of endotoxin to activate KC causes a drastic reduction of graft survival. Together, KC activation and endothelial damage cause marked microcirculatory disturbances after transplantation characterized by reduced and uneven blood flow and increased leucocyte and platelet adhesion. Such events culminate in inflammation, necrosis and fulminant graft failure. Modification of reperfusion conditions can reduce the extent of injury. In particular, flushing livers with Carolina rinse solution (CRS) at the end of storage reduces endothelial cell killing, suppresses KC activation, improves the microcirculation, and increases graft survival. Active ingredients in CRS include antioxidants (allopurinol, desferrioxamine and glutathione), adenosine and slightly acidic pH (6.5). Other potentially important ingredients are nicardipine, a calcium channel blocker, and fructose, glucose and insulin to promote glycolysis. The cytoprotective amino acid, glycine, further improves the performance of Carolina rinse solution. Reperfusion‐induced changes to nonparenchymal cells play an essential role in damage to livers preserved for transplantation surgery. Understanding the role of sinusoidal endothelial cells and KC in this injury has led to promising new strategies to prolong organ storage and reduce graft fail

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1995.tb01808.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe cause of primary graft non‐function after orthotopic liver transplantation (OLTX) is uncertain, but its clinical features are similar to fulminant hepatic failure with coagulopathy. In preserved livers, endothelial cell damage in the hepatic sinusoids is characteristic, indicating that fibrin deposition in the hepatic sinusoids, which can cause massive hepatic necrosis, might occur in the liver after OLTX. When rat liver was preserved in University of Wisconsin solution at 1°C, detachment of endothelial linings into sinusoidal lumens developed with fat‐storing cell damage after 18 h. In this liver, hepatic macrophages were activated after reperfusion. Tissue factor activity in hepatic macrophages isolated from livers after OLTX was significantly increased compared to the control liver and this increase was enhanced by addition of endotoxin. In the preserved and transplanted livers, thrombomodulin expression in endothelial cells disappeared and fibrin deposition was seen in the hepatic sinusoids. Intravenous infusion therapy with antithrombin III attenuated liver injury 24 h after OLTX following preservation for 18 h. These results suggest that intravascular coagulation in the hepatic sinusoids associated with liver injury occurs in the liver after OLTX following cold preservation. This coagulopathy may be caused by sinusoidal endothelial cell damage due to regulatory imbalance in coagulation as a result of increased tissue factor activity in hepatic macrophages and decreased thrombomodulin activity in sinusoidal endothelial cells. Fat‐storing cell damage may also contribute to the endothelial cell damage. A hypothesis regarding the cause of primary graft non‐function after OLTX is

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1995.tb01809.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractPrimary graft non‐function of the liver is one of the common causes of retransplantation. Although the mechanism of primary graft non‐function is not fully understood, a potent elucidative pathogenesis is microcirculatory disturbance due to sinusoidal damage during cold preservation and reperfusion. In this article, we discuss the possible participation of sinusoidal endothelial cells and Kupffer cells (KC) in the cold preservation/reperfusion injury. Kupffer cell activation and endothelial damage were developed during the cold preservation with subsequent reperfusion. Activated KC produced a large quantity of tumour necrosis factor (TNF)α, and then increased ICAM‐1 expression in sinusoidal endothelial cells. The reperfusion experiment showed that hypercoagulability and leucocyte adherence in the liver are strongly involved in reperfusion injury, and that KC blockade as well as anti‐TNFα antibody and anti‐ICAM‐1 antibody ameliorate the injury in association with a reduction of both fibrin deposition and leucocyte accumulation. Ultrastructural observation also revealed the beneficial effect of KC blockade on the maintenance of sinusoidal endothelial cells. Furthermore, the thromboxane A2‐thromboxane A2 receptor system in the sinusoid was also found to participate in this pathogenesis. Thus, these results suggested that cold preservation/reperfusion injury is due to sinusoidal microcirculatory disturbance, which is, at least in part, induced by communication between activated KC and sinusoidal endothelial cells through, among others, ICAM‐1, cytokine

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1995.tb01810.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractIn several experimental models, lipopolysaccharide (LPS) plays an important role in the pathogenesis of liver diseases. Murine models of C3H/HeN and C3H/HeJ mice have been used to elucidate the role of LPS and its responsive‐macrophagesin vivo, as C3H/HeN strain mice are known to be LPS‐responsive, while C3H/HeJ strain mice are LPS‐resistant. Furthermore, release of several kinds of biologically active mediators such as interleukin‐1, tumour necrosis factor‐α, colony stimulating factor and reactive oxygen radical is not enhanced in C3H/HeJ mice even after stimulation with LPS. Thus, these murine models could be suitable for clarification of endotoxin induced cellular communication in

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1995.tb01811.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY