Long-term consequence of rat orthotopic liver transplantation with and without hepatic arterial reconstruction: A clinical, pathological, and hemodynamic study
Authors: H Imamura
Journal: Hepatology (1997)

and the availability of inbred strains, rat OLT has become a Our aim was to investigate the time-related changes in varipowerful model to study the mechanisms of graft rejection ous parameters following orthotopic rat liver transplantation and preservation-induced injury. with (AOLT) and without (NOLT) arterial reconstruction inAlthough the model of rat OLT using cuff anastomosis male Lewis rats.Body weight and biochemical parameters appears to be well standardized, controversy still seems to were measured weekly, and a liver biopsy was obtained at 4, exist as to the importance of hepatic arterial reconstruction.8, and 12 weeks.Hemodynamics were evaluated at 12 weeks Previous reports have shown that rat OLT without hepatic using the microsphere technique and compared with matched arterial reconstruction resulted in biliary tract complications, controls.Following AOLT, rats gained weight normally withas evidenced by abnormal biochemical markers, 3 histological out any noticeable complication.In NOLT, two subgroups changes similar to those observed in secondary biliary cirrho-(NOLT-1 and NOLT-2) could clearly be identified retrospecsis, [3][4][5][6] and increased postoperative mortality. 3,6On the other tively.In the NOLT-1 group, the body weight increased norhand, other groups have not found any significant difference mally, although animals presented transient cholestasis.In between the structural integrity, 7,8 liver function, 8 and surthese rats, the ductular proliferation found at 4 weeks had vival 7 of rats with arterialized OLT or with nonarterialized regressed by the 12th week with near-normal biopsies.By OLT. contrast, in the NOLT-2 group, rats did not gain body weightThis equivocal postoperative evolution in the rat is not and had persistent cholestasis.Marked ductular proliferation seen in humans in whom early loss of arterial blood, followwith increasing fibrosis was observed, resulting in a secondary ing transplantation, generally leads to massive liver necrosis biliary cirrhosis by the 12th week.Surprisingly, rearterializaif retransplantation is not performed within a short time.tion of the grafted liver occurred in both NOLT-1 and NOLT-Interestingly, ligature of the hepatic artery in the rat has no 2 irrespective of their clinical course.All transplanted rats immediate or long-term effect on liver structure, 4 probably showed portal hypertension with marked portosystemic because of collateral arterial supplies. 9Moreover, rearterialshunts, probably caused by the portal cuff.However, a hyperization of the grafted liver was shown to occur spontaneously dynamic circulatory state was only observed in the NOLT-2 within 3 weeks after surgery. 10,11group with cirrhotic changes.These findings further show Using morphometric analysis, Zhao et al. 4,12 reported that the combined role of an intact hepatic innervation and of no architectural abnormalities were found following arterialhepatocellular insufficiency in the genesis of the hyperdyized OLT, while severe bile duct damage was observed in namic circulatory state associated with portal hypertension.rats following nonarterialized OLT, reaching a maximum at HEPATOLOGY 1997;26:198-205.) 4 weeks and then regressing over 6 months.In the latter animals, regression of bile duct damage was associated with The orthotopic liver transplantation (OLT) technique in a spontaneous graft rearterialization, 12 suggesting a causal the rat was first described by Lee et al., 1 and further facilitated relationship.However, these authors also reported that the by Kamada et al. 2 by the introduction of the cuff technique regression of bile duct damage was accompanied by an infor portal vein anastomosis.Because of its technical feasibility crease in fibrosis, which reached a maximum at 6 months following nonarterialized OLT. 4,12Therefore, the regression of bile duct damage can conversely be interpreted as a phenomenon normally expected in the late phase of this patho-Abbreviations: OLT, orthotopic liver transplantation; AOLT, orthotopic liver translogical entity.Indeed, following the initial stage of proliferaplantation with arterial reconstruction; NOLT, orthotopic liver transplantation without tion, both bile ducts and ductules are known to disappear arterial reconstruction; HCS, hyperdynamic circulatory state.