Novel strategy to decrease reperfusion injuries and improve function of cold‐preserved livers using normothermic ex vivo liver perfusion machine

Normothermic extracorporeal liver perfusion (NELP) can decrease ischemia reperfusion injury to the greatest degree when cold ischemic time is minimized. Warm perfusion of cold-stored livers results in hepatocellular damage, sinusoidal endothelial cell (SEC) dysfunction and Kupffer cell activation. However, the logistics of organ procurement mandates a period of cold preservation prior to NELP. The aim of this study was to determine the beneficial effects of gradual rewarming of cold-stored livers by placement on NELP. Three female porcine livers were used for each group. In the Immediate-NELP group, procured livers were immediately placed on NELP for 8 hours. In the Cold-NELP group, livers were cold stored for 4 hours followed by NELP for 4 hours. In rewarming groups, livers were cold stored for 4 hours, then gradually rewarmed in different durations to 380C and kept on NELP for additional 4 hours. For comparison purposes the last four hours of NELP runs were considered as the evaluation phase. Immediate-NELP livers had significantly lower concentrations of liver transaminases, hyaluronic acid, β-galactosidase, and had higher bile production compared to the other groups. Rewarming livers had significantly lower concentration of hyaluronic acid and β-galactosidase compared to the Cold-NELP livers. In addition, there was a significant decline in INR values, improved bile production, reduced biliary epithelial cell damage and improved cholangiocyte function. Thus, if NELP machine is not available at the procurement site and livers will need to undergo a period of cold preservation; a gradual rewarming protocol prior to NELP may greatly reduce damages that are associated with reperfusion. In conclusion, gradual rewarming of cold-preserved livers upon NELP can minimize the hepatocellular damage, Kupffer cell activation and SEC dysfunction. This article is protected by copyright. All rights reserved.