Experimental Liver Preservation with Celsior:A Novel Alternative to University of Wisconsin and Histidine-Tryptophan-α-Ketoglutarate Solutions?

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Abstract
Celsior, a low viscosity and low potassium preservation solution, has recently been tested successfully in the cold preservation of heart, lung, kidney and small intestine. The purpose of the present study was to evaluate the potential of Celsior in the cold preservation of the liver. Livers were harvested from male Wistar rats and then flushed with either Celsior (CE), University of Wisconsin solution (UW) or histidine-tryptophan-α-ketoglutarate solution (HTK) and stored for 24 h at 4°C in the respective solution. The reperfusion was performed in vitro using a recirculating model with oxygenated (95% O2, 5% CO2) Krebs-Henseleit buffer at 37°C. To simulate the slow rewarming during the surgical implantation in vivo, all livers were stored for 30 min at room temperature prior to reperfusion. After ischemic storage and also after reperfusion some samples were freeze-clamped for analysis of tissue metabolites while others were tested for structural and functional integrity by the isolated perfusion. CE vs. UW vs. HTK: Metabolic preservation of tissue ATP (μmol/g dry weight) during cold storage was best with Celsior (0.46 ± 0.17 vs. 0.26 ± 0.03 vs. 0.35 ± 0.07; p < 0.05 CE vs. UW), but upon reperfusion energetic recovery was comparable in the three groups (3.45 ± 0.66 vs. 4.27 ± 0.41 vs. 3.63 ± 0.64 μmol/g/dry weight). There appeared to be structural integrity during reoxygenation irrespective of the used preservation solution with comparable values of parenchymal enzyme release (ALT: 575 ± 82 vs. 547 ± 106 vs. 593 ± 38 mU/g/l), bile production (18.0 ± 1.0 vs. 18.5 ± 2.5 vs. 18.7 ± 1.4 μl/g/ min), and the release of acid phosphatase, an indicator for activated Kupffer cells (89 ± 13 vs. 90 ± 5 vs. 123 ± 21 mU/g/l) in this in vitro model. Vascular flow characteristics were approximated by the portal perfusion pressure, which tended to be elevated upon initial reperfusion in the UW group (8.4 ± 0.6 mm Hg) compared to 6.6 ± 1.0 and 7.3 ± 0.4 mm Hg in Celsior and HTK, respectively. However, the pressure values decreased to the normal range even in the UW group with ongoing perfusion. The sensitivity of our model in detecting protective effects of the tested solution was confirmed by a negative control group of livers stored in Ringer’s solution at 4°C, yielding an impaired recovery which differed by one magnitude from the three other groups. Within the limits of an in vitro study it is concluded from these results that Celsior may become a suitable alternative for liver preservation and further studies including a transplantation in vivo are strongly encouraged.

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