The preventive effects of the calcium channel blocker, verapamil, on ischemic liver damage were studied using a rat total hepatic ischemic model. A marked improvement in the survival was obtained by verapamil administration. Following 90 min of hepatic ichemia, 8 of 9 rats (89%) survived in the verapamil-treated group compared to only a 50% survival rate in the saline-treated control group. Furthermore, 56% of the rats still survived after 120 min of ischemia, while there was no survivor in the control group. The recovery of hepatic ATP level following ischemia was significant in the verapamil-treated group, showing the well-preserved mitochondrial function afforded by verapamil administration.

A unique case of hepatolithiasis associated with cholangiocarcinoma is described. The intrahepatic calculi consisted mainly of cholesterol rather than calcium bilirubinate. A bacteriological study of the intrahepatic and gallbladder bile was negative, though bacterial infection of the bile duct has been considered a main factor responsible for formation of intrahepatic calculi.

Treatment of macrophages with cytochalasin E in combination with a lectin was found to stimulate the generation of superoxide anions (021 very efficiently. The macrophages stimulated with concanavalin A, phytohemagglutinin or wheat germ agglutinin released superoxide, but cells pretreated with cytochalasin E released much greater amounts of superoxide, without notable lag time, upon stimulation with the lectin.Wheat germ agglutinin was found to be the most efficient stimulant among the lectins tested.Superoxide generation in guinea pig macrophages was shown to be dependent largely on cytoplasmic glucose metabolism and to some extent on mitochondrial respiration, since the superoxide release was largely but not totally inhibited by 2-deoxyglucose and to a lesser extent by antimycin A or KCN.The method presented is sensitive and allows rapid assay of the superoxide-generating activity with only 1-5 x 105 macrophages for a single determination.In application of this technique, elevation of the superoxide-generating activity was shown with macrophages elicited by chemical inflammation or those obtained from mice after treatment with tubercle bacilli.

The protective effects of PGEl on ischemia-related liver damage were evaluated in dogs. Ninety minutes warm hepatic ischemia was induced by the total clamping of hepatic inflow vasculatures with portal bypassing. The survival rate improved up to 62.5% when PGEl was administered intravenously prior to ischemia, while no dog survived for longer than 1 week in the nontreated group. Hepatic ATP content was restored up to 80% of preischemic level 2 h after reflow in the PGEl pretreated group, compared to 55% recovery in the nontreated group. Complete normalization of hepatic energy charge and rapid decrease of lactate were also seen in the PGEl group. The clearance rate of intravascular lipid emulsion remained fairly normal in the PGE 1 group, thereby suggesting well-preserved hepatic reticuloendothelial functions. The serum activities of P-glucuronidase, GOT and GPT were suppressed in the PGE 1 -pretreated group, thereby implying a well-protected hepatic integrity. The histology revealed well-preserved hepatic architecture. The remarkable cytoprotective effect of PGEl on hepatic ischemia shown in this study indicates that PGEl warrants further study for protection of ischemically compromised hepatic allografts. 193-201. tology 1984 4: 66s-71s. 12:

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