Progressively increasing discrepancy between the number of effective donors and the number of patients requiring transplantation leads to use of allografts from extended criteria donors. This fact leads to an increase of early allograft dysfunction, the level of biliary complications, and a decrease of graft survival.

Objective. To assess the effect of various preservation methods on the degree of ischemic damage to liver grafts.

Materials and methods. During the case-control study, the effect of hypothermic oxygenated machine perfusion and static cold storage on the degree of liver cells damage was assessed. Liver transplants that were recognized as extended criteria during the multi-organ retrieval procedure were explanted according to the classical method and were preserved with static cold storage (SCS) for the period of transportation. During the “back-table” procedure, a complete separation of the liver parenchyma along the Cantle line was performed. After randomization by random number method, one part was preserved with static cold storage at a temperature of 40C (control group, n = 10), and the second was preserved by hypothermic oxygenated machine perfusion through the portal vein with 2 liters of Belzer UW MPS solution at a temperature from +4 to + 10 ° C, perfusion pressure 3 mmHg, 100% O2 flow – 1 l / min, pO2 = 34.7 ± 1.1 kPa for 4 hours (study group, n = 10). The sampling of effluent and parenchyma biopsies for biochemical and morphological evaluation were performed at the beginning of the study, after 2 and 4 hours after the start of the experiment in both groups.

Results. The use of hypothermic oxygenated machine perfusion for 4 hours at the end of static cold storage reduces the level reactive oxygen species and as well as the level of AST, ALT, LDH in comparison with static cold storage alone.

Conclusion. It was found that the use of hypothermic machine perfusion can reduce the degree of ischemic liver grafts damage.

1. Asrani SK, LarsonKim, W. R., Therneau, T. M., Benson, J. T., Kremers, W. K., Rosen, C. B., Gores, G. J., & Dickson, E. R. (2006). Deaths on the liver transplant waiting list: an analysis of competing risks. Hepatology (Baltimore, Md.), 43(2), 345–351. https://doi.or JJ, Yawn B, Therneau TM, Kim WR. Underestimation of liver-related mortality in the United States. Gastroenterology. 2013;145(2):372–375. doi: 10.1053/j.gastro.2013.04.005

2. DeLemos AS, Vagefi PA. Expanding the donor pool in liver transplantation: Extended criteria donors. Clin Liver Dis. 2013;2(4):156–159. doi: 10.1002/cld.222

3. Weeder PD, Van Rijn R, Porte RJ. Machine perfusion in liver transplantation as a tool to prevent non-anastomotic biliary strictures: Rationale, current evidence and future directions. J Hepatol. 2015;63(1):265–275. doi: 10.1016/j.jhep.2015.03.008

4. Olschewski P, Gass P, Ariyakhagorn V, и др. The influence of storage temperature during machine perfusion on preservation quality of marginal donor livers. Cryobiology. 2010;60(3):337–343. doi: 10.1016/j.cryobiol.2010.03.005

5. Schlegel A, Kron P, Dutkowski P. Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application. Curr Transplant Reports. 2015;2(1):52–62. doi: 10.1007/s40472-014-0046-1

6. Van Rijn R, Van Leeuwen OB, Matton APM, и др. Hypothermic Machine Preservation of the Liver: State of the Art. J Surg Res. 2018;223:263–274. doi: 10.1016/j.jss.2017.11.052

7. Lipowsky HH, Lescanic A. The Effect of Doxycycline on Shedding of the Glycocalyx Due to Reactive Oxygen Species. Microvasc Res. 2013;90. doi: 10.1016/j.mvr.2013.07.004

8. Petrowsky H, Clavien PA. Principles of Liver Preservation. Transplant Liver Third Ed. 2015:582–599. doi: 10.1016/B978-1-4557-0268-8.00044-0

9. Устройство для консервации донорской ткани в условиях гипотермии: пат. 11222 Респ. Беларусь: МПК A01N 1/02 / А. М. Федорук, Н. М. Яковец, В. А. Ленкевич, Е. В. Гулевич, Д. А. Федорук, Л. В. Кирковский, О. О. Руммо; дата публ.: 30.10.2016.

10. Menasche P, Termignon JL, Pradier F, et al. Experimental evaluation of Celsior, a new heart preservation solution. Eur J Cardiothorac Surg. 1994;8(4):207.

11. Vekemans K, et al. Artificial circulation of the liver: machine perfusion as a preservation method in liver transplantation. Anat Rec (Hoboken). 2008 Jun;291(6):735–40. doi: 10.1002/ar.20662.

12. Van Golen RF, van Gulik TM, Heger M. Mechanistic overview of reactive species-induced degradation of the endothelial glycocalyx during hepatic ischemia/reperfusion injury. Free Radic Biol Med. 2012;52(8):1382.

13. Saelens X, Festjens N, Vande Walle L, van Gurp M, van Loo G, Vandenabeele P. Toxic proteins released from mitochondria in cell death. Oncogene. 2004;23(16):2861.

14. Arnoult D, Gaume B, Karbowski M, Sharpe JC, Cecconi F, Youle RJ. Mitochondrial release ofAIF and EndoG requires caspase ac- tivation downstream of Bax/Bak-mediated permeabilization. EMBO J. 2003;22(17):4385.

15. Van Gurp M, Festjens N, van Loo G, Saelens X, Vandenabeele P. Mitochondrial intermembrane proteins in cell death. Biochem Biophys Res Commun. 2003;304(3):487.

16. Porter A.G., Jänicke R.U. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999 Feb;6(2):99–104.

17. Monbaliu D, Vekemans K, De Vos R, et al. Hemodynamic, bio- chemical, and morphological characteristics during preservation of normal porcine livers by hypothermic machine perfusion. Transplant Proc. 2007;39(8):2652.

18. Dirkes MC, Post IC, Heger M, van Gulik TM. A novel oxygenated machine perfusion system for preservation of the liver. Artif Organs. 2013;37(8):719.