Long-term cold liver storage induces endothelin-1 release and a time-dependent increase in portal pressure at reperfusion in the rat.
BACKGROUND
Long-term cold storage and reperfusion lead to great liver injury involving major microcirculatory disturbance. This study investigated the effect of storage duration on endothelin-1 production, portal pressure, and microcirculation.


METHODS
Rat livers were perfused before and after 15 min to 48 h of cold storage in University of Wisconsin (UW) solution.


RESULTS
Portal pressure was unchanged for up to 12 h of storage, and increased by 40% and 70% after 24 and 48 h, respectively. Vascular space was increased by a factor of 1.7 following 48 h of storage. Endothelin-1 was released by livers stored in UW solution for 48 h (3.99 +/- 1.85 pg/100 microl). The nonselective endothelin-1 receptor antagonist TAK-044 partially prevented the increase in portal pressure and prevented the increase in vascular space.


CONCLUSIONS
Cold storage induces a time-dependent elevated portal pressure at reperfusion. The involvement of endothelin-1 in this process offers opportunities to improve liver graft quality by using endothelin-1 inhibitors.
Charrueau
Christine A
CA
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Carayon
Alain
A
Thurman
Ronald G
RG
D000818:Animals; D015925:Cryopreservation; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology*; D016031:Liver Transplantation; D008833:Microcirculation / Q000503:physiopathology; D017082:Portal Pressure / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013997:Time Factors
D019332:Endothelin-1