Michelle Meier1, Kasper Jarlhelt Andersen2, Anders Riegels Knudsen2, Jens Randel Nyengaard3, Stephen Hamilton-Dutoit4, Frank Viborg Mortensen2. 1. Department of Surgical Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: michellemeiermd@gmail.com. 2. Department of Surgical Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. 3. Stereology & Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark. 4. Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Abstract
BACKGROUND: The upper limit for the size of hepatectomy is approximately 90% in rats. The aim of the study was to assess quantitatively using stereological methods the impact on liver function, regeneration rate (RR), and hepatocyte proliferation of varying hepatectomy size in a rat model. MATERIALS AND METHODS: A total of 104 male Wistar rats were subjected to 30%, 70%, or 90% partial hepatectomy, sham operation, or no operation. Euthanization and harvesting of liver tissue and blood took place at postoperative days 1, 3, and 5 (n = 8 per group). Liver-specific biochemistry and RR were evaluated. Hepatocyte proliferation was estimated by immunohistochemical staining for Ki-67 antigen using unbiased stereological principles. RESULTS: Liver RR in the 90% group increased by a 6.6 fold during the 5 postoperative days compared with only a minor increase in both the 70% and 30% partial hepatectomy groups. The highest number of Ki-67-positive hepatocytes was observed in the 70% group at postoperative day 1 and for the 90% group at postoperative day 3. Prothrombin-proconvertin ratio was significantly lower in the 90% group 1 d after surgery compared with all other groups, however, nearly normalized at postoperative day 5. CONCLUSIONS: We show that liver RR and the number of proliferating hepatocytes increase, whereas the initial hepatic synthetic capacity decreases with increasing hepatectomy size.
BACKGROUND: The upper limit for the size of hepatectomy is approximately 90% in rats. The aim of the study was to assess quantitatively using stereological methods the impact on liver function, regeneration rate (RR), and hepatocyte proliferation of varying hepatectomy size in a rat model. MATERIALS AND METHODS: A total of 104 male Wistar rats were subjected to 30%, 70%, or 90% partial hepatectomy, sham operation, or no operation. Euthanization and harvesting of liver tissue and blood took place at postoperative days 1, 3, and 5 (n = 8 per group). Liver-specific biochemistry and RR were evaluated. Hepatocyte proliferation was estimated by immunohistochemical staining for Ki-67 antigen using unbiased stereological principles. RESULTS: Liver RR in the 90% group increased by a 6.6 fold during the 5 postoperative days compared with only a minor increase in both the 70% and 30% partial hepatectomy groups. The highest number of Ki-67-positive hepatocytes was observed in the 70% group at postoperative day 1 and for the 90% group at postoperative day 3. Prothrombin-proconvertin ratio was significantly lower in the 90% group 1 d after surgery compared with all other groups, however, nearly normalized at postoperative day 5. CONCLUSIONS: We show that liver RR and the number of proliferating hepatocytes increase, whereas the initial hepatic synthetic capacity decreases with increasing hepatectomy size.