Einfluss des hydrophilen Gallensalzes Tauroursodesoxycholat auf die Zusammensetzung von Gallenflüssigkeit : Studie in einem In-Vivo-Transplantationsmodell beim Schwein
Duisburg-Essen (2005), 77 Bl.
Dissertation / Fach: Medizin
Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Allgemeinchirurgie, Viszeral- und Transplantationschirurgie
Broelsch (Doktorvater, Betreuerin)
Postoperative complications within the biliary tract remain a significant problem after liver transplantation despite advances in operative techniques. A significant cause for these complications appear to be hydrophobic bile salts, which remain in the bile ducts after organ harvest. These are believed to exert membrane damaging effects on the bile duct tissue. Hydrophilic bile salts, in contrast, have tissue protective properties. Earlier studies have shown that perioperative infusion of the hydrophilic bile acid Tauroursodeoxycholate (TUDC) positively influences liver function parameters and the histologic appearance of bile ducts. This is believed to be due to TUDC’s own membrane stabilizing effects, as well as to a displacement of hydrophobic bile salts from the bile fluid. Until now, there had been no studies into how bile fluid composition changes after perioperative infusion of TUDC in liver transplantations. This knowledge would allow conclusions regarding how TUDC acts and would aid with the development of therapeutic options for the prevention of bile duct complications. To investigate postoperative concentrations of hydrophilic and hydrophobic bile acids in the bile fluid, the livers of 12 pigs were transplanted. Before explantation and after reperfusion, animals of the experimental group (n=6) received TUDC iv, animals of the control group (n=6) received infusions of Normal Saline of equal length and rate. Bile samples were analyzed using High-Performance Liquid Chromatography (HPLC). Postoperative concentrations of TUDC were significantly higher in the experimental group, while there were no significant differences in the concentrations of the other investigated hydrophilic bile salts. In contrast, the concentrations of hydrophobic bile salts were markedly reduced in the experimental group, in two cases significantly (Taurochenodeoxycholate, Glycochenodeoxycholate). The results show both a shift in bile fluid composition away from the hydrophobic bile salts, and an increase in TUDC concentrations, which would support the membrane-stabilizing effect of TUDC. These results can be applied in the development of new techniques to reduce bile duct damage after liver transplantation. Further research will be required before clinical application.
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