Liver transplantation in the rat: single-center experience with technique, long-term survival, and functional and histologic findings.
OBJECTIVE
Orthotopic liver transplantation (OLT) in rats is frequently used as an experimental model. Numerous surgical techniques have been developed that enable the investigator to conduct clinically relevant studies. The objective of this study was to develop a rat model of acute and chronic rejection, to explicitly study technical modifications of vascular anastomoses with precision, and to examine histopathologic and functional changes in the graft.


METHODS
With DA-(RT1av1) rats as donors and Lewis-(RT1) rats as recipients, arterialized OLT was performed using a combined suture, cuff, and splint method. Recipients were divided into 5 groups: syngeneic control rats (group 1), allogeneic control rats (group 2), allogeneic OLT rats with low-dose tacrolimus (FK506) immunosuppression (group 3), allogeneic OLT rats with high-dose tacrolimus immunosuppression (group 4), and allogeneic OLT rats with high-dose tacrolimus immunosuppression and retrograde reperfusion via the infrahepatic caval vein (group 5). After OLT, serum parameters were determined and hepatic biopsy specimens were sampled. We examined the effects of acute rejection with or without immunosuppression therapy at histopathologic evaluation.


RESULTS
Liver grafts in syngeneic and allogeneic rats (groups 1, 2, 4, and 5) demonstrated normal serum parameters and histopathologic findings at 10 days after OLT, and 93% survival at 3 months. The simplified technique using 1 suture and 2 cuff anastomoses provided the best short- and long-term survival after OLT in all groups. Retrograde perfusion via the infrahepatic caval vein resulted in lower postoperative liver enzyme values.


CONCLUSIONS
The present model is feasible, enabling comprehensive preclinical experimental research on liver transplantation. Furthermore, we provide helpful instructions for learning this surgical technique.
Matevossian
E
E
Department of Surgery, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany. matevossian@chir.med.tu-muenchen.de
Doll
D
D
Hüser
N
N
Brauer
R
R
Sinicina
I
I
Nährig
J
J
Friess
H
H
Stangl
M
M
Assfalg
V
V
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000401:mortality / Q000473:pathology / Q000502:physiology*; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D016559:Tacrolimus