DUCTULAR REACTION AT THE EARLY AND LATE STAGES OF BILIARY OBSTRUCTION: IS THE MECHANISM THE SAME?

Ductular reaction (DR) is one of the classical features of biliary obstruction in humans as well as in experimental models. It is the histological phenomenon expressed by the increased number of ductular profiles (DPs), which is especially intensively studied in rodents' model of common bile duct ligation (CBDL). However, some issues related with DR in long-term CBDL are not clear enough. The liver tissue of male Wistar rats (150-200 g) subjected to CBDL were studied histologically (H&E). The architectonics of the biliary tract was studied by investigation of the corrosion casts obtained by retrograde injection (trough CBD) the solidified mass prepared on the basis of "Protacryl M" widely implemented in orthopedic dentistry. The casts were investigated by electro-optic device ProScope-HR with magnification X10, X50 and X200. DR accompanying CBDO is featured by the development of new DPs, the number of which is permanently increased in association with the prolongation of the terms of Cholestasis. DPs continue to develop in all areas of liver lobules - from portal/periportal region up to the regions containing central veins (hepatic veins tributaries of small calibers). The part of DPs has wide lumens, while the lumens of another part of DPs are hardly notable. In spite of evident ductular metaplasia of hepatic tissue, the small groups of normal by form and structure hepatocytes forming the separate small islets could be revealed. Histological features of these hepatocytes support the proposition that these cells maintain the functional activity on the 4th-5th weeks after CBDO. The results of investigations of biliary corrosion casts on the 4th and 5th weeks of CBDO show that solidifying mass cannot reach the small ducts/ductules and especially bile canaliculi. This fact confirms the interruption of ductular-canalicular junctions (IDCJ). We propose that due to IDCJ the increased pressure in preserved bile canaliculi should stipulate the mitotic activity and biliary trans-differentiation of hepatocytes on the late terms of CBDO and support the generation of ductal-like structures and appearance of new DPs. These ductules generally are not drained into the entire biliary tree.

[Optimization of the venous return during experimental hepatectomy in rabbits].

A traditional bypass pattern applied in hepatectomy (venous return in superior vena cava system) is frequently attended by blood congestion in cranial veins. The study objective is the maintenance of hemodynamic indices in normal physiological ranges via application of the new bypass scheme in the experimental model of the anhepatic period. 12 rabbits of Chinchilla breed were involved in the experiments, with weight ranging between 3,0-3,5 kg, which were divided into three groups (with 3 animals in each): I control group - hepatectomy under the condition of non-compulsory liver bypass with the return of the venous flow in brachiocephalic vein. II group - hepatectomy with the compulsory bypass, with an in-take of blood in the apparatus and injection in the brachiocephalic vein. III group - hepatectomy via non-traditional method of compulsory bypass in suprahepatic vena cava. The outcomes of the experiments indicated that blood congestion in cranial venous system occurred only in I and II groups, which was verified by the pressure rise (5,9+/-1,2 mmHg and 4,7+/-0,5 mmHg, respectively) and diminished blood flow rate (3,0+/-1,8 ml/min and 2,0+/-0,7 ml/min) in external jugular vein. These indices corresponded with the levels of 0,6+/-0,2 mm Hg and 9,0+/-2,5 ml/min respectively in the III group. Application of the artificial, compulsary bypass circuit has been established to be reasonable in anhepatic period, for achieving the blood return to the heart through portal vein and from the lower parts of the body. During blood return in suprahepatic portion of vena cava, the congestion in cranial venous system is prevented. Maintenance of the pressure and volume indices between normal physiological limits in venous system provides the opportunity of safe prolongation of the anhepatic period.

Biliary hypertension as the cell proliferation trigger in bile duct ligated rats.

The aim of the study was to investigate the relationship between biliary pressure dynamics and proliferative activity of cholangiocytes and hepatocytes in BDL setting. 30 white Wistar male rats, weighting 200-220 gr. were involved in the modelled biliary hypertension setting induced by common bile duct ligation (CBD). The pressure in CBD was measured before (I) and at 1st (II), 3rd (III), 72nd (IV), 96th (V), 120th (VI) and 144 th (VII) hours after its ligation, with following data registered respectively: 169.67+/-4.16 (I), 205.0+/-1.0 (II), 213.67+/-3.06 (III), 252.67+/-3.51 (IV), 270.67+/-2.52 (V), 277.33+/-3.21 (VI) and 285.67+/-2.52 (VII) mm H(2)O. Pressure in portal vein was measured before (I) and at 1st (II), 6th (III), 24th (IV), 72nd (V) and 144 th (VI) hours past the bile flow obstruction. The corresponding indices were: 103.67+/-3.51 (I), 107.33+/-4.16 (II), 123.33+/-2.08 (III), 58.00+/-1.73 (IV), 172.00+/-3.61 (V) and 190.67+/-4.93 (VI) mm H(2)O. Liver histology was studied on paraffin embedded and Hand E stained slides in every above mentioned terms of CBD ligation. Mitotic indices for proliferating cholangiocytes and hepatocytes were counted at 24th, 48th, 72nd, 96th and 144 th hours after CBD ligation. The outcomes revealed that ductular reaction appears just in the first hours after CBD ligation. However the mitoses of epitheliocytes reach their peak (18.0+/-1.3) at 3rd day but mitoses of hepatocytes (31.5+/-2.1) - at 4th day after bile flow obstruction. Consequently, the following conclusions were made: biliary and portal hypertension, induced by the first respectively, represent the proliferative triggers for biliary ductules, cholangiocytes and hepatocytes in common biliary duct occlusion setting; However, dynamics, as well as the mechanisms of this process require further comprehensive investigation, including not only reduced inter-experimental term intervals and refinement of morphological and/or molecular - biological techniques of the study, but also the development of new, different experimental models.