Does Liver Transplantation in the Rat Cause a Regenerative Response

摘要

This study was conducted to determine the pattern of early regenerative response to orthotopic intactliver transplantation in the rat and to investigate whether the response differed in grafts with or withoutrevascularisation of the arterial bed.Outbred male Long Evans (LE-LE allogeneic, non rejector) rats weighing 300–350g were subjectedto orthotopic intact liver allograft using a “sleeve” anastomosis for the hepatic artery. Total warmischaemia ranged from 19 to 34 minutes and no storage was employed. Comparison was made with agroup of control rats which were subjected to 25 minutes total inflow occlusion and regeneration wasmeasured with tissue thymidine kinase (TK) and mitotic figures. Samples were taken at 1,2,4,7,10 and20 days post-operatively. Plasma aspartate aminotransferase (AAT) and light microscopy were used toevaluate hepatocyte necrosis. There was a brief sharp increase in TK and AAT in the first 24 hours aftersham operation but no appearance of mitotic figures. A similar but more prolonged increase in TKoccurred in the arterialised transplant group with the highest levels recorded on day 4. The levelremained significantly elevated above pre-operative until 10 days and declined within 20 days. Mitoticfigures appeared at 2 days, reached significance at 7 and 10 days and had disappeared by 20 days. Thepattern of changes was accentuated in animals in which the artery was not reanastomosed and theincreases in TK and AAT were still significant at 20 days. Whilst similar degrees of peri-portal cellularinfiltrate occurred in both groups of rats, bile duct proliferation was most obvious in non-arterialisedanimals.As compared with a previously prepared group of partially hepatectomised animals, the regenerativeresponse after liver transplant was delayed and prolonged especially in the non-arterialised group.It is concluded that a regenerative response occurred in liver allografts in rats soon after operation,which was slightly prolonged if the hepatic artery was not anastomosed and that the response seemed tobe related to hepatocyte damage which occurred as part of the procedure. The relevance of thesefindings to clinical liver transplantation is discussed.