TY - JOUR
T1 - Cold ischemia decreases liver regeneration after partial liver transplantation in the rat
T2 - A TNF-α/IL-6-dependent mechanism
AU - Selzner, Nazia
AU - Selzner, Markus
AU - Tian, Yinghua
AU - Kadry, Zakiyah
AU - Clavien, Pierre Alain
N1 - Funding Information:
Abbreviations: IL-6, interleukin 6; TNF-α, tumor necrosis factor α; rIL-6, recombinant interleukin 6; PCNA, proliferating cell nuclear antigen; BrdU, bromodeoxyuridine; HPF, high-power field. From the Department of Visceral Surgery and Transplantation, University of Zürich, Zürich, Switzerland. Received April 17, 2002; accepted June 24, 2002. Supported by a grant from the National Institutes of Health (DK54048-01A1 to P.-A.C.) and the Swiss National Science Foundation (SNF3200-061411 to P.-A.C.). N.S. is supported by grants from EMDO and Theodor and Ida Herzog-Egli, Switzerland. Address reprint requests to: Pierre-Alain Clavien, M.D., Ph.D., F.A.C.S., Department of Visceral Surgery and Transplantation, University of Zurich, Rämistr. 100, 8091 Zürich, Switzerland. E-mail: [email protected]; fax: (41) 1 255 4449. Copyright © 2002 by the American Association for the Study of Liver Diseases. 0270-9139/02/3604-0006$35.00/0 doi:10.1053/jhep.2002.35535
PY - 2002/10/1
Y1 - 2002/10/1
N2 - New strategies of partial liver transplantation such as cadaveric split or living related liver transplantation have been developed to overcome organ shortage. Thus, studies on the ability of small partial grafts to regenerate to normal size while maintaining adequate function have become important. Here, we evaluated the effects of cold preservation on hepatocyte proliferation and function in a novel model of partial liver transplantation in rats. Lewis rats subjected to 70% liver resection (control) were compared with rats that underwent total hepatectomy and 30% partial liver transplantation (recipient). Livers were preserved at 4°C for 30 minutes, 10 hours, or 16 hours in University of Wisconsin solution. Seventy percent liver resection was associated with 100% survival, whereas 30-minute, 10-hour, and 16-hour preservation before 30% transplantation resulted in 80%, 40%, and 20% animal survival, respectively. Prolonged time of cold preservation (10 and 16 hours) was associated with a dramatic decrease of all markers of regeneration (P < .05). Tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels were also significantly decreased in recipient rats compared with the control group. Finally, pretreatment of recipients with recombinant IL-6 (rlL-6) normalized all markers of regeneration and significantly improved survival in the 10-hour group (90% vs. 40%; P < .05). In conclusion, sustained periods of cold preservation significantly impaired TNF-α and IL-6 production, the regenerative ability of the liver, and animal survival. rIL-6 reversed impaired regeneration in the 10-hour cold ischemia group and suggests a primary role of nonparenchymal cells in modulating hepatocyte proliferation in the ischemic liver.
AB - New strategies of partial liver transplantation such as cadaveric split or living related liver transplantation have been developed to overcome organ shortage. Thus, studies on the ability of small partial grafts to regenerate to normal size while maintaining adequate function have become important. Here, we evaluated the effects of cold preservation on hepatocyte proliferation and function in a novel model of partial liver transplantation in rats. Lewis rats subjected to 70% liver resection (control) were compared with rats that underwent total hepatectomy and 30% partial liver transplantation (recipient). Livers were preserved at 4°C for 30 minutes, 10 hours, or 16 hours in University of Wisconsin solution. Seventy percent liver resection was associated with 100% survival, whereas 30-minute, 10-hour, and 16-hour preservation before 30% transplantation resulted in 80%, 40%, and 20% animal survival, respectively. Prolonged time of cold preservation (10 and 16 hours) was associated with a dramatic decrease of all markers of regeneration (P < .05). Tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels were also significantly decreased in recipient rats compared with the control group. Finally, pretreatment of recipients with recombinant IL-6 (rlL-6) normalized all markers of regeneration and significantly improved survival in the 10-hour group (90% vs. 40%; P < .05). In conclusion, sustained periods of cold preservation significantly impaired TNF-α and IL-6 production, the regenerative ability of the liver, and animal survival. rIL-6 reversed impaired regeneration in the 10-hour cold ischemia group and suggests a primary role of nonparenchymal cells in modulating hepatocyte proliferation in the ischemic liver.
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U2 - 10.1053/jhep.2002.35535
DO - 10.1053/jhep.2002.35535
M3 - Article
C2 - 12297828
AN - SCOPUS:0036789438
SN - 0270-9139
VL - 36
SP - 812
EP - 818
JO - Hepatology
JF - Hepatology
IS - 4I
ER -