Gentle organ manipulation during harvest as a key determinant of survival of fatty livers after transplantation in the rat.
Both in situ organ manipulation during harvest and steatosis reduce survival after liver transplantation via mechanisms involving Kupffer cells; thus, their effect on survival was compared here. Moderate steatosis was induced by a single dose of ethanol to Lewis rats, while long-term administration of ethanol yielded severe steatosis in donor animals. After minimal dissection during the first 12 min, livers were either manipulated gently or left alone for 13 min subsequently. Orthotopic liver transplantation was performed after 1 h of cold storage in UW solution. Ethanol increased hepatic lipid content to a level of moderate or severe steatosis that reduced survival after transplantation from 100% to approximately 70% (P < 0.05). However, gentle manipulation decreased survival to approximately 30% (P < 0.05) in livers from normal, saline-treated rats and in livers from rats fed a high-fat control diet. Moreover, after short- or long-term ethanol administration, manipulation of fatty livers decreased survival from 70% to approximately 13% (P < 0.05). Further, manipulation elevated serum transaminases, total bilirubin, and necrosis significantly about 2- to 20-fold in fatty grafts after transplantation. At the end of harvest, trypan blue distribution time and hypoxia assessed from 2-nitroimidazole binding were elevated significantly about two- to fourfold by manipulation of fatty grafts. Gadolinium chloride, a Kupffer cell toxicant, blocked the detrimental effects of manipulation. These data demonstrate for the first time that, while steatosis is detrimental for survival, organ manipulation plays a much greater role than fat in mechanisms of primary nonfunction.
Schemmer
P
P
Laboratory of Hepatobiology, Department of Pharmacology, CB 7365, Mary Ellen Jones Bldg., University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Schoonhoven
R
R
Swenberg
J A
JA
Bunzendahl
H
H
Raleigh
J A
JA
Lemasters
J J
JJ
Thurman
R G
RG
D000818:Animals; D015687:Cell Hypoxia; D000431:Ethanol / Q000633:toxicity; D005234:Fatty Liver / Q000503:physiopathology*; D005260:Female; D006085:Graft Survival; D007728:Kupffer Cells / Q000502:physiology; D016031:Liver Transplantation; D051381:Rats; D011917:Rats, Inbred Lew
D000431:Ethanol