Normothermic extracorporeal liver perfusion (NELP) is able to decrease ischemia reperfusion injury to the greatest degree when cold ischemic time is minimized. However, given the logistics of organ procurement, a period of cold preservation prior to placement on NELP is inevitable. Rapid rewarming of the liver after cold storage results in hepatocellular damage. The aim of this study was to investigate the effects of gradual versus rapid rewarming of livers as it is placed on NELP after cold storage. Livers from 9 female landrace pigs were divided into 3 experimental groups. In group 1, the livers were placed immediately on NELP 4 hours, followed by a 4 hour evaluation phase on NELP. In group 2, the livers were stored at 4°C for 4 hours and then rapidly rewarmed on NELP for 4 hours of perfusion. In group 3, the livers were similarly cold-stored for 4 hours followed by 4 hours of NELP, but the liver underwent a 25 minute gradual rewarming phase at the transition. We used the final 4 hours on NELP as the evaluation phase in all groups (i.e., functional reperfusion period). Group 1 livers had significantly lower liver transaminases, hyaluronic acid, β-galactosidase, lactate and TNF-α, and had better bile production compared to the other two groups. In the livers which underwent an initial 4 hours of cold storage, the group 3 livers which underwent gradual rewarming had significantly lower liver transaminases, TNF-α, hyaluronic acid and β-galactosidase compared to the group 2 rapidly rewarmed livers. In addition, there was significant decline in lactate and INR values (Table 1). Interestingly, histologic examination of the group 3 livers showed reduced IRI with minimal sinusoidal dilatation and lobular inflammation by the end of assessment phase, while the group 2 livers had findings consistent with moderate IRI. These data suggest that a gradual rewarming of cold preserved livers when placed upon NELP can improve the metabolic and functional parameters of livers and minimize the hepatocellular damage in comparison to a rapid rewarming strategy.

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