Gentle in situ liver manipulation during organ harvest decreases survival after rat liver transplantation: role of Kupffer cells.
BACKGROUND
The etiology of primary graft nonfunction and dysfunction is unknown but most likely involves Kupffer cell-dependent reperfusion injury. However, the donor operation and surgical technique may also have an effect on the outcome after transplantation. Because liver manipulation during harvest cannot be prevented completely with standard procedures, its effect on survival was assessed here.


METHODS
Donor livers were harvested from female Sprague-Dawley rats (200-230 g). Briefly, after minimal dissection during the first 12 min, livers were either manipulated gently or left alone for 13 subsequent minutes. At 25 min, all livers were perfused with cold University of Wisconsin solution via the portal vein, and transplantation was performed after cold storage (1 hr). In some rats, Kupffer cells were destroyed with gadolinium chloride or inactivated with dietary glycine before harvest. Survival, proteolytic activity in the rinse effluent, serum transaminases, trypan blue distribution to index microcirculation, and histology were compared.


RESULTS
In the nonmanipulated group, survival was 100% after transplantation; however, gentle manipulation decreased survival by 70%. Further, manipulation elevated transaminases fivefold and caused about 200% necrosis. At harvest, proteolytic activity and the time for trypan blue to distribute homogeneously were elevated three- to eightfold by manipulation. Gadolinium chloride and glycine prevented the effects of manipulation on all parameters studied.


CONCLUSIONS
These data indicate for the first time that brief, gentle manipulation of the donor liver has a marked detrimental effect on survival by priming or activating Kupffer cells. This may represent an important early event in pathogenesis, because Kupffer cells play an important role in primary graft nonfunction.
Schemmer
P
P
Department of Pharmacology, University of North Carolina at Chapel Hill, 27599-7365, USA.
Schoonhoven
R
R
Swenberg
J A
JA
Bunzendahl
H
H
Thurman
R G
RG
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D016923:Cell Death; D004210:Dissection; D005260:Female; D005682:Gadolinium / Q000633:toxicity; D005978:Glutathione; D005998:Glycine / Q000494:pharmacology; D006085:Graft Survival; D006498:Hepatectomy / Q000379:methods*; D000860:Hypoxia; D007328:Insulin; D007728:Kupffer Cells / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000473:pathology* / Q000502:physiology; D008102:Liver Circulation / Q000502:physiology; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology*; D008833:Microcirculation / Q000502:physiology; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions; D011887:Raffinose; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005682:Gadolinium; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; C038958:gadolinium chloride; D005998:Glycine