Ischemic Preconditioning of Rat Livers from Non-Heart-Beating Donors Decreases Parenchymal Cell Killing and Increases Graft Survival after Transplantation
A critical shortage of donors exists for liver transplantation, which non-heart-beating cadaver donors could help ease. This study evaluated ischemic preconditioning to improve graft viability after non-heart-beating liver donation in rats. Ischemic preconditioning was performed by clamping the portal vein and hepatic artery for 10？min followed by unclamping for 5？min. Subsequently, the aorta was cross-clamped for up to 120？min. After 2？h of storage, livers were either transplanted or perfused with warm buffer containing trypan blue. Aortic clamping for 60 and 120？min prior to liver harvest markedly decreased 30-day graft survival from 100% without aortic clamping to 50% and 0%, respectively, which ischemic preconditioning restored to 100 and 50%. After 60？min of aortic clamping, loss of viability of parenchymal and nonparenchymal cells was 22.6 and 5.6%, respectively, which preconditioning decreased to 3.0 and 1.5%. Cold storage after aortic clamping further increased parenchymal and non-parenchymal cell killing to 40.4 and 10.1%, respectively, which ischemic preconditioning decreased to 12.4 and 1.8%. In conclusion, ischemic preconditioning markedly decreased cell killing after subsequent sustained warm ischemia. Most importantly, ischemic preconditioning restored 100% graft survival of livers harvested from non-heart-beating donors after 60？min of aortic clamping. 1. Introduction Liver transplantation surgery is a viable alternative for patients with end-stage liver disease but the number of heart-beating cadavers suitable for liver donation remains a key limitation. In human kidney transplantation, organ donation from non-heart-beating cadavers is now employed successfully at many centers [1]. Organ donors are typically terminally ill patients who do not meet the criteria of brain death and whose life support is withdrawn at the request of the family. After cardiac arrest occurs and death is pronounced several minutes later, the organs are harvested. The use of livers from non-heart-beating donors is also emerging as an important stratagem to expand the liver donor pool [2]. Organs from non-heart-beating cadaver donors typically experience several minutes of warm ischemia prior to cold preservation. Warm ischemic injury that occurs to livers after cardiac arrest can severely compromise graft viability. Early clinical results with livers from non-heart-beating donors were poor, and two-month graft survival was only 50% even for donors that were extubated in an operating room setting [3]. With more rapid organ harvesting, clinical outcomes have
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