Reperfusion injury after liver preservation for transplantation

Abstract

Preservation injury remains an obstacle to greater utilization of liver transplantation therapy. Livers can be preserved a maximum of 24 h in University of Wisconsin solution. After longer times, reperfusion precipitates endothelial cell killing and activation of Kupffer cells (liver macrophages). Together, Kupffer cell activation and endothelial cell killing cause microcirculatory disturbances, leukocyte and platelet adhesion, and a systemic inflammatory response after graft implantation. Down-regulation of Kupffer cells with calcium blockers or pentoxifylline improves graft survival, whereas priming with lipopolysaccharide or alcohol worsens survival. Flushing grafts after storage with Carolina rinse solution containing antioxidants, adenosine, calcium blocker, energy substrates, and glycine at pH 6.5 decreases endothelial cell killing, reduces Kupffer cell activation, and improves graft survival. Understanding of the roles of different cells in storage/reperfusion injury forms the basis for strategies to prolong organ storage, improve graft function, and reduce failure of fatty grafts from alcoholic donors.