Five hundred ninety-three cadaveric livers were used for primary liver transplantation between October 24, 1987, and May 19, 1989. The grafts were procured with a combined method, using in situ cooling with cold electrolyte solution and backtable flushing with UW solution. The mean cold-ischemia time was 12.8 (range 2.4-34.7) hr. The cases were divided into 5 groups according to the cold-ischemia time: group 1: less than 10 hr (n = 223); group 2: 10-14 hr (n = 188); group 3: 15-19 hr (n = 101); group 4: 20-24 hr (n = 52); and group 5: greater than or equal to 25 hr (n = 29). There was no difference between the 5 groups in 1-year patient survival, highest SGOT in first week after operation, and SGOT and total bilirubin during the first month after operation. However, with a logistic regression model, the retransplantation rate (P = 0.001) and primary nonfunction rate (P = 0.006) significantly rose as cold-ischemia time increased, meaning that the equivalency of patient survival was increasingly dependent on aggressive retransplantation.

Incubation of normal plasma low-density lipoprotein (LDL) with erythrocytes results in echinocyte formation; the effect is attributed to stimulation of spectrin dephosphorylation through binding of LDL to the cell surface (Hui & Harmony, 1979, Biochimica et Biophysica Acta, 550, 407). No shape change occurs when erythrocytes are incubated with normal highdensity lipoprotein (HDL) and LDL-induced echinocyte formation is inhibited by HDL. We have established that as a consequence of abnormal apoprotein composition (an increased content of ApoE and threonine-poor apoproteins) the HDL of liver disease competes with LD L for binding by the high-affinity receptor on cultured skin fibroblasts. In the present study we have determined whether the abnormal HDL of liver disease (d = 1·063-1·21) will induce echinocyte formation in normal erythrocytes.HDL from several patients which showed the apoprotein abnormalities were tested; all induced marked echinocyte formation when added to a suspension of normal erythrocytes at 37°C (6 x 10 9 cells/ml and 500 ug ofHDL-protein/ml). Patient HDL was 10-100 times more potent than normal LDL and could transform 100% of the cells. Echinocyte formation was rapid (less than 10 s), occurred to a similar extent at 4°C and was also induced by partially delipidated patient HDL. The erythrocyte binding site differed from that on cultured fibroblasts; echinocyte formation was not inhibited by protamine or heparin and also occurred when apoprotein arginine residues were blocked with cyclohexanedione or when erythrocytes from patients with homozygous familial hypercholesterolaemia were used. The morphological changes were associated with increased osmotic resistance and with decreased membrane fluidity as measured by a hydrophobic, fluorescent probe. Attempts to restore biconcave disc morphology by addition of heparin or normal HDL were only moderately successful.Previous studies have implicated changes in erythrocyte membrane lipid composition as underlying the 'spur-cell anaemia' of liver disease (Cooper, Arner, Wiley & Shattil, 1975, Journal of Clinical Investigation, 55, 115); our results suggest that abnormal HDL apoprotein composition may also play a role. DECREASED ER YTHROCYTE MEMBRANE FLUIDITY AND ALTERED LIPID COMPOSITION IN HUMAN LIVER DISEASEAbnormal plasma lipoproteins in patients with liver disease are associated with characteristic changes in erythrocyte membrane lipid composition. The membranes are enriched in cholesterol and lecithin and both the cholesterol/phospholipid (C/P) and lecithin/sphingomyelin (LlSM) molar ratios are increased. Phospholipid fatty acid composition is also abnormal; the proportion of arachidonic acid is decreased and that of palmitic acid raised. In this study we have examined the effects of these membrane lipid abnormalities on membrane fluidity.Erythrocyte membrane fluidity was assessed in 30 patients with a variety of liver diseases, and in 25 normal subjects by using the hydrophobic, fluorescent probe I,6-diphenyl hex a-1,3,5-triene, and the value...

In an effort to define the mechanism by which thyroid hormone increases the synthesis of hepatic cholesterol, we have investigated both in hypophysectomized and methimazole-treated hypothyroid rats the time course of T3 effects on plasma cholesterol concentration, total hepatic cholesterol, the rate of biliary secretion of cholesterol, bile acids, and phospholipids, and the activity and mRNA levels of 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase, the rate-limiting enzyme in the hepatic synthesis of cholesterol. A single dose of 200 micrograms T3 was estimated to maintain at least 90% nuclear occupancy for the ensuing 54 h of the experiment. In both preparations the relative rise in biliary secretion of cholesterol exceeded that of other biliary constituents and preceded by 12 h an increase in HMG-CoA reductase enzyme activity and its mRNA. The level of total hepatic cholesterol remained constant throughout the experiment. We interpret these findings to suggest that T3-stimulated cholesterol synthesis is mediated by an antecedent T3-induced rise in biliary cholesterol secretion. We postulate that biliary cholesterol secretion is augmented by an intrahepatic shift of cholesterol and depletion of the hepatic sampling center responsible for the feedback regulation of cholesterol synthesis. The level of HMG CoA reductase mRNA appeared to govern enzyme activity in both preparations, but the ratio of mRNA to hepatic enzyme activity was substantially greater in the methimazole-treated compared with the hyphophysectomized animals.

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