Extended preservation and effect of nitric oxide production in liver transplantation.
Liver transplantation (Ltx) has become a routine procedure for patients with end-stage liver disease. Despite ongoing progress on short- and long-term graft survival, primary dysfunction (PDF) remains a major problem. PDF is significantly associated with the duration of cold ischemia- and, possibly, with reperfusion-related injury. Nitric oxide (NO) has many physiological functions and plays an important role in modulating tissue injury. However, the mechanism of NO action in ischemia/reperfusion injury after Ltx is thus far unknown. In this study we investigated the role of inducable NO synthase (iNOS) in the liver after preservation with UW solution using the orthotopic Ltx model in the rat. Male Brown Norway rats were used for the Ltx procedure. After donor hepatectomy, livers were stored on ice-cold UW solution for 24 or 40 h and subsequently transplanted. A control group consisted of rats with Ltx after less than 1 h storage. Post-transplant blood samples were taken at 48 h to determine standard parameters for liver injury (aspartate transaminase, lactate dehydrogenase). Liver biopsies were obtained for detection of expression of iNOS (western blot) 24 and 48 h post-transplant. We observed that a preservation time of 24 h in UW solution presents no problem for graft survival after Ltx in rats with some brain function and in healthy animals. After 40 h preservation, liver damage is obvious and graft survival reduced, indicating the limits of cold storage may be within reach. With longer preservation times, more NOs was detected in liver tissue. This finding suggests that NO has a role in ischemia/reperfusion-related injury. Current intervention with NOS inhibitors will reveal whether NO has a negative or a positive effect on graft survival after Ltx.
Department of Surgery, University Hospital Groningen, The Netherlands.
J A
JA
van der Hoeven
S
S
Lindell
P T
PT
van Suylichem
T
T
Vos
G G
GG
Groothuis
H
H
Moshage
R J
RJ
Ploeg
D000818:Animals; D003080:Cold Temperature; D006085:Graft Survival; D016031:Liver Transplantation / Q000401:mortality / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D009926:Organ Preservation; D051381:Rats; D011914:Rats, Inbred BN; D015996:Survival Rate; D013997:Time Factors
D009569:Nitric Oxide