Geller D A, Chia S H, Takahashi Y, Yagnik G P, Tsoulfas G, Murase N
Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pennsylvania 15213, USA.
JPEN J Parenter Enteral Nutr. 2001 May-Jun;25(3):142-7. doi: 10.1177/0148607101025003142.
A major problem complicating liver transplantation is the preservation injury that results from cold storage and subsequent ischemia/reperfusion injury after organ revascularization. The L-arginine-nitric oxide (NO) pathway has been recognized to play critical roles during infection, inflammation, organ injury, and transplant rejection. Recent data indicates that NO synthesis has beneficial effects in several models of liver injury. The purpose of this study is to examine the role of the L-arginine-NO pathway on preservation injury in an experimental model of rat liver transplantation.
Orthotopic liver transplantation was performed in syngeneic (LEW to LEW) rats. Liver preservation injury was determined by measuring serum liver function tests 6 to 48 hours after transplantation. In some experiments, rats received L-arginine supplementation 0 to 24 hours after transplantation. In other experiments, NO synthase inhibitors (L-NAME or L-NIL) were injected at the time of isograft revascularization.
L-Arginine supplementation decreased hepatic transaminase levels at all time points examined (6-48 hours). L-Arginine produced a significant improvement in liver preservation injury by 12 hours after reperfusion. The NO synthase inhibitor L-NAME caused a significant increase in liver injury 24 hours after injection. The inducible NO synthase (iNOS)-specific inhibitor L-NIL had no significant effect on liver injury.
The results show that L-arginine supplementation and NO synthesis improve hepatic injury and have a protective role in the transplanted liver graft. The protective effect may be mediated by low-level cNOS-derived NO.
