PMID: 8589353Jan 1, 1995Paper

Dual role of Kupffer cell activation and endothelial cell damage in reperfusion injury to livers stored for transplantation surgery

Journal of Gastroenterology and Hepatology
J J LemastersR G Thurman

Abstract

In 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 ...Continue Reading

References

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Citations

Mar 1, 1995·Liver Transplantation and Surgery : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·J J LemastersR G Thurman
Sep 2, 2003·Gastroenterology·Nazia SelznerPierre-Alain Clavien
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·J J Lemasters, R G Thurman
Jan 10, 2012·HPB : the Official Journal of the International Hepato Pancreato Biliary Association·Nhut Quang TranVijayaragavan Muralidharan
Dec 24, 2010·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Helge BrunsPeter Schemmer
Feb 7, 2006·The Journal of Surgical Research·Payam Samareh PahlavanJannis Kountouras
Nov 26, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y KumamotoM Kitajima
Jun 27, 2003·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Ronald W Busuttil, Koichi Tanaka
Feb 4, 2010·Current Opinion in Organ Transplantation·Olivier de RougemontPierre-Alain Clavien
May 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D SindramP A Clavien

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