Reperfusion rather than storage injury predominates following long-term (48 h) cold storage of grafts in UW solution: studies with Carolina Rinse in transplanted rat liver.
Both storage injury and reperfusion injury have been reported in association with liver transplantation; however, which predominates is not clear. Therefore, these studies were designed to evaluate whether Carolina Rinse, which minimizes reperfusion injury following orthotopic liver transplantation in the rat, would be effective after long-term (48 h) storage of grafts in University of Wisconsin (UW) cold storage solution where sufficient time for development of storage injury exists. Livers were rinsed with either Ringer's solution or Carolina Rinse solution immediately prior to completion of implantation surgery. In the Ringer's group, 30-day survival was high following 24 h of cold storage (4/5) but was very low after 48 h (1/16). Importantly, survival was increased significantly (5/14) when grafts were rinsed with Carolina Rinse following 48 h of cold storage. In both groups, parenchymal cells appeared normal by scanning electron microscopy, excluded trypan blue, and released SGOT at values only slightly above the normal range immediately (i.e., less than 5 min) after 48 h of cold storage. However, SGOT values rose steadily during the 1st hour postoperatively following reperfusion in the Ringer's rinse group and reached levels around 1,000 U/l. In addition, nonparenchymal cells were not labelled with trypan blue following storage, but significant labelling occurred within 1 h. Both SGOT release and nonparenchymal cell injury were reduced significantly when grafts were rinsed with Carolina Rinse prior to completion of surgery. Liver injury assessed histologically 24 h postoperatively was also reduced about 50% by Carolina Rinse. Oxidative stress appeared to be involved, since radical adducts, most likely of lipid origin, were trapped during the first 5 min after reperfusion with the spin trapping technique and detected by electron paramagnetic resonance spectroscopy. Lipid radical formation was reduced nearly completely on reperfusion by Carolina Rinse. Since Carolina Rinse improved survival of liver grafts following long periods of cold storage and reduced lipid radical formation and hepatocellular injury, we concluded that a reperfusion injury rather than a storage injury predominates following orthotopic transplantation of livers stored for long periods of time in cold UW solution.
Gao
W
W
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, The University of North Carolina at Chapel Hill, NC 27599-7365, USA.
Currin
R J
RJ
Lemasters
J J
JJ
Connor
H D
HD
Mason
R P
RP
Thurman
R G
RG
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D005978:Glutathione; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D007328:Insulin; D008099:Liver / Q000187:drug effects; D016031:Liver Transplantation / Q000379:methods* / Q000502:physiology; D019188:Organ Preservation Solutions; D011887:Raffinose; D051381:Rats; D015424:Reperfusion / Q000379:methods*; D015427:Reperfusion Injury / Q000517:prevention & control*; D012996:Solutions / Q000494:pharmacology
C070887:Carolina rinse solution; D007328:Insulin; D019188:Organ Preservation Solutions; D012996:Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose