Urea and protein synthesis in cold-preserved isolated rat hepatocytes.
We used an isolated-hepatocyte model to study how hypothermic storage (simulating liver preservation) affects metabolism after prolonged preservation. Rat hepatocytes were stored in the University of Wisconsin solution for up to 72 hr. After each day of storage, protein synthesis, urea synthesis, ATP content and lactate dehydrogenase release were determined in rewarmed (37 degrees C) and oxygenated hepatocytes. Protein synthesis ([3H]-leucine incorporation into protein) was depressed by 16% +/- 4%, 54% +/- 6% and 69% +/- 4% after 24 hr, 48 hr and 72 hr, respectively. Urea synthesis, ATP synthesis and lactate dehydrogenase release were similar to those in control hepatocytes (no preservation). Fasting of the rats before isolation of hepatocytes caused more rapid loss of protein-synthesis capabilities (59% in 24 hr) with no significant loss of lactate dehydrogenase, urea synthesis or ATP synthesis. Hepatocyte viability (lactate dehydrogenase release) as judged by membrane permeability, ATP synthesis and potassium content can be maintained after up to 6 days of cold storage. However, protein synthesis is depressed after only 48 hr of cold storage. Thus hypothermic storage of the liver causes a change in the metabolic capabilities of the hepatocytes, and the timing of the loss of protein synthesis is similar to the limits of successful cold storage of the whole liver (48 hr). Thus a limit to long-term storage of the liver may be related to loss of protein synthesis. In liver transplantation, one indication of poor preservation is a decrease in serum albumin and clotting factors with increased tissue edema and bleeding diathesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Vreugdenhil
P K
PK
Department of Surgery, University of Wisconsin, Madison 53792.
Marsh
D C
DC
Belzer
F O
FO
Southard
J H
JH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003080:Cold Temperature; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007930:Leucine / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014021:Tissue Preservation; D014316:Tritium; D014508:Urea / Q000378:metabolism*
D014316:Tritium; D000255:Adenosine Triphosphate; D014508:Urea; D007770:L-Lactate Dehydrogenase; D007930:Leucine