We compared the impact of cold static liver preservation vs subnormothermic ex vivo liver perfusion (SNEVLP) on outcome of DCD pig liver transplantation (LT). Methods: 45min cardiac arrest was induced in pigs as a model of DCD organ retrieval. We compared 10 hr cold static preservation with 7hr cold preservation plus 3hr SNEVLP. Pig LT was performed after preservation. Hepatocyte, endothelial cell (EC), and bile duct injury were assessed by H&E staining, immunohistochemistry (CD31, Caspase 3, TUNEL) and AST. Beta galactosidase was determined as a marker of Kupffer Cell (KC) activation. Hepatic artery thrombus formation was assessed by MSB staining. ATP and Glycogen were determined. Results: 45min of warm ischemia reduced liver ATP and glycogen levels to 20% and 15% of baseline. After 2hr of SNEVLP preservation ATP and glycogen content increased to 90% and 60% of baseline. 8hr after LT SNEVLP vs cold stored livers had decreased serum AST levels (387+151 vs 934+ 459U/L, p<0.01) and reduced hepatocyte necrosis (15% vs 45% p<0.01). SNEVLP preservation resulted in decreased caspase 3 (16 cells/HPF vs. 46 cells/HPF, p<0.01) and TUNEL (14 cells/HPF vs. 47.25 cells/HPF, p<0.01) positive cells as markers of apoptosis. Microthrombosis within the peribiliary arteries was observed in cold stored organs (4/5 livers) but not in SNEVLP treated grafts (0/5 livers). CD31 staining demonstrated severe EC injury in cold stored grafts, while EC lining was preserved in SNEVLP treated DCD livers. After 3hr of reperfusion beta galactosidase (KC activation) was significantly reduced in SNEVLP (95.65+ 41.61 vs 325.99 + 187.75, p=0.012) stored grafts. Hourly bile production after transplantation was significant higher in SNEVLP treated grafts (9.58+3.83 ml vs 6.43+3.42ml; p<0.01). Bile ducts necrosis (75%) was present in 3 out of 5 cold stored livers, while no bile duct injury was detected in SNEVLP preserved (p<0.01). Conclusion: SNEVLP improves hepatic energy content in DCD liver grafts during preservation and reduces hepatocyte, endothelial cell and bile duct injury after LT.
To cite this abstract in AMA style:Knaak J, Boehnert M, Spetzler V, Kim B, Louis K, Eid C, Selzner N, Oyedele A, Yip P, Keshavjee S, Grant D, Selzner M. Subnormothermic Ex Vivo Liver Perfusion (SNEVLP) Reduces Ischemia/Reperfusion Injury in Livers Retrieved after Cardiac Death [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/subnormothermic-ex-vivo-liver-perfusion-snevlp-reduces-ischemiareperfusion-injury-in-livers-retrieved-after-cardiac-death/. Accessed May 16, 2021.
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