Does Liver Transplantation in the Rat Cause a Regenerative Response

This study was conducted to determine the pattern of early regenerative response to orthotopic intact liver transplantation in the rat and to investigate whether the response differed in grafts with or without revascularisation of the arterial bed. Outbred male Long Evans (LE-LE allogeneic, non rejector) rats weighing 300–350g were subjected to orthotopic intact liver allograft using a “sleeve” anastomosis for the hepatic artery. Total warm ischaemia ranged from 19 to 34 minutes and no storage was employed. Comparison was made with a group of control rats which were subjected to 25 minutes total inflow occlusion and regeneration was measured with tissue thymidine kinase (TK) and mitotic figures. Samples were taken at 1,2,4,7,10 and 20 days post-operatively. Plasma aspartate aminotransferase (AAT) and light microscopy were used to evaluate hepatocyte necrosis. There was a brief sharp increase in TK and AAT in the first 24 hours after sham operation but no appearance of mitotic figures. A similar but more prolonged increase in TK occurred in the arterialised transplant group with the highest levels recorded on day 4. The level remained significantly elevated above pre-operative until 10 days and declined within 20 days. Mitotic figures appeared at 2 days, reached significance at 7 and 10 days and had disappeared by 20 days. The pattern of changes was accentuated in animals in which the artery was not reanastomosed and the increases in TK and AAT were still significant at 20 days. Whilst similar degrees of peri-portal cellular infiltrate occurred in both groups of rats, bile duct proliferation was most obvious in non-arterialised animals. As compared with a previously prepared group of partially hepatectomised animals, the regenerative response 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 to be related to hepatocyte damage which occurred as part of the procedure. The relevance of these findings to clinical liver transplantation is discussed.