Assessment of hepatic viability during cold ischemic preservation.
A reliable and easy method for assessing the viability of a cold ischemia-preserved donor liver prior to transplantation into the recepient is needed. Based on an earlier study, we hypothesized that liver free fatty acid (FFA) leakage into the preservation fluid may be a useful, atraumatic indicator of irreversible ischemic injury. The aim of the present study was to determine the time course and magnitude of liver FFA release into the preservation solution and its correlation with the duration of cold ischemic preservation compatible with survival after transplantation. Rat livers (n = 48) were flushed and preserved with University of Wisconsin (UW) solution at 4 degrees C for 0, 12, 24, and 48 h. Thereafter, half of the livers were analyzed for preservation fluid FFA (gas-liquid chromatography) and protein. The other half were perfused with Krebs-Henseleit (KH) solution at 37 degrees C for 1 h. Bile secretion and liver enzyme release (SGOT, SGPT, and LDH) were measured in addition to perfusate FFA and protein. Total FFA in the preservation fluid was 24 micrograms/g wet tissue after 12 h; it increased sharply 2.6-fold after 24 h and 3.7-fold after 48 h of preservation. Bile production was normal after 12 h of preservation but fell by 20% and 54% after 24 h and 48 h, respectively. LDH release rose from a value of 20 U/l at 0 time to 120 U/l and 260 U/l after 24 h and 48 h of preservation. These results suggest that liver viability declines sharply between 12 and 24 h of cold ischemic preservation, which corresponds with a sharp decrease in the 1-week survival from 100% to 33% after 12 h and 24 h, respectively, of cold ischemic preservation. We conclude that measuring FFA and LDH in the preservation solution of donor livers may be a useful means of assessing the quality of the cold-preserved liver before insertion into the recipient. We also speculate that a "threshold" FFA level in the UW preservation fluid indicating irreversible damage may be in the order of 35 micrograms total FFA/g liver. Studies on the clinical applicability of our findings are currently under way.
Hamamoto
I
I
Department of Surgery, University of Pittsburgh, School of Medicine, PA 15261, USA.
Nemoto
E M
EM
Zhang
S
S
Hartwell
V R
VR
Todo
S
S
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D003080:Cold Temperature; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology; D006085:Graft Survival / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose