REPERFUSION INJURY AFTER LIVER PRESERVATION FOR TRANSPLANTATION

Preservation injury remains an obstacle to greater utilization of live r transplantation therapy. Livers can be preserved a maximum of 24 h i n University of Wisconsin solution. After longer times, reperfusion pr ecipitates endothelial cell killing and activation of Kupffer cells (l iver macrophages). Together, Kupffer cell activation and endothelial c ell killing cause microcirculatory disturbances, leukocyte and platele t adhesion, and a systemic inflammatory response after graft implantat ion. Down-regulation of Kupffer cells with calcium blockers or pentoxi fylline improves graft survival, whereas priming with lipopolysacchari de or alcohol worsens survival. Flushing grafts after storage with Car olina rinse solution containing antioxidants, adenosine, calcium block er, energy substrates, and glycine at pH 6.5 decreases endothelial cel l killing, reduces Kupffer cell activation, and improves graft surviva l. Understanding of the roles of different cells in storage/reperfusio n injury forms the basis for strategies to prolong organ storage, impr ove graft function, and reduce failure of fatty grafts from alcoholic donors.