Role of Kupffer cells in cold ischemia/reperfusion injury of rat liver.
OBJECTIVE
Kupffer cell activation is hypothesized to play an etiopathogenic role in storage-related graft failure after liver transplantation. The aim of this study was to verify whether the elimination of Kupffer cells modifies the magnitude of cold ischemia/reperfusion injury of the liver.


METHODS
Rat Kupffer cells were eliminated by an intravenous injection of liposome-encapsulated dichloromethylene diphosphonate. Livers from control and treated rats were isolated and perfused before and after 24-hour cold ischemia in the University of Wisconsin solution (4 degrees C). Hepatocyte and sinusoidal endothelial cell functions were evaluated by taurocholate and hyaluronic acid elimination, respectively. Liver transplantation was also performed using control and treated donor livers stored under identical conditions.


RESULTS
Compared with baseline values, similar alterations were found in both groups after cold ischemia for hepatocyte function (intrahepatic resistance, bile secretion, lactate dehydrogenase release, oxygen consumption, and taurocholate intrinsic clearance) and for sinusoidal endothelial cell function (hyaluronic acid intrinsic clearance). The 10-day survival rate of animals undergoing transplantation was not different between the groups (6 of 15 vs. 4 of 15, control vs. treated donor livers, respectively).


CONCLUSIONS
The presence or absence of Kupffer cells does not modify the effect of 24-hour cold ischemia/reperfusion on the rat liver.
Imamura
H
H
André-Viallet Clinical Research Center, Hôpital Saint-Luc, Montreal, Quebec, Canada.
Sutto
F
F
Brault
A
A
Huet
P M
PM
D000241:Adenosine; D000493:Allopurinol; D000704:Analysis of Variance; D000818:Animals; D001646:Bile / Q000378:metabolism; D005978:Glutathione; D006820:Hyaluronic Acid / Q000493:pharmacokinetics; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D007328:Insulin; D007511:Ischemia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007728:Kupffer Cells / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation; D008262:Macrophage Activation; D008297:Male; D008657:Metabolic Clearance Rate; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D010101:Oxygen Consumption; D011887:Raffinose; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013656:Taurocholic Acid / Q000493:pharmacokinetics; D014022:Tissue Survival
D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D013656:Taurocholic Acid; D000493:Allopurinol; D006820:Hyaluronic Acid; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose